Foundations 1 Flashcards

Question

What differentiates free ribosomes from ER bound ribosomes?

Answer 1

They are structurally identical and it only depends on which protein they are currently translating. If it is bound for the ER the ribosome will move to the ER and if not the ribosome will remain free.

Answer 2

ER, golgi, lysosomes, endosomes and cell surface

Answer 3

When the protein begins to be translated, the beginning N terminus will contain a signal sequence for the ER. The signal sequence is recognized by signal recognition particle (SRP) which binds to an SRP receptor on the ER membrane which allows the growing protein to pass through a translocator as it is translated. signal sequence --> signal recognition particle (SRP) --> SRP receptor --> translocator--> ER

Answer 4

Soluble proteins pass completely through the membrane as they are translated and end up free floating within the ER. These proteins are ultimately bound for the lumen of an organelle or else to be secreted outside of the cell completely. Embedded proteins are held in the ER membrane after translation based on transmembrane portions. These proteins will be membrane bound in their destination and are transferred to their final location by vessicular transport.

Answer 5

As it is being translated, a hydrophobic stop sequence occurs causing the translocator to "spit" the protein out into the surrounding membrane. This hydrophobic portion remains embedded into the membrane while the protein continues to be translated anchoring the protein there. A single protein may have several stop hydrophobic stop and start sequences causing it to make multiple passes through the membrane.

Answer 6

Signal peptidase

Answer 7

Symptoms: XY individuals form female external genitalia but no ovaries Cause: non-functional SRY gene Connection: May result from lack of nuclear localization signal on SRY gene causing the gene to not perform its function in the nucleus as a transcription factor

Answer 8

An endonuclease recognizes the sequence AAUAAA and cleaves at this site allowing polyadenylate polymerase to add a poly A tail.

Answer 9

More than 1 codon code for the same amino acid

Answer 10

Insertion and deletion mutations at the protein level refer to addition or deletion of 1 or more amino acids without causing a frameshift whereas frameshift mutations occur when a number of nucleotides not divisible by 3 was added or deleted from the reading frame which shifts the reading frame causing major changes to the product.

Answer 11

A group of ribosomes that are working independently of each other to translate the same piece of mRNA.

Answer 12

One vertical line coming from the sibling line with two diagonal lines to individuals represents twins. Monozygotic twins will have a horizontal line between them while dizogotic twins will not

Answer 13

It represents that a mating couple are related by blood. It is represented by a double mating line instead of the normal single line

Answer 14

That person is deceased

Answer 15

Make sure it follows all of the normal rules (squares = male circle female, mating lines etc.)

Answer 16

DNA Histones Non-histone proteins

Answer 17

They are not always exactly the same but are constantly changing leading to changes in gene expression patterns

Answer 18

A “bead” made up of 8 histones with DNA wrapped around it

Answer 19

The binding of sister chromatids together. Cohesin protein complex accomplishes this by acting like a napkin ring around sister chromatids

Answer 20

Mitosis - Cohesion loads onto sister chromatids at replication - majority dissociates at prophase but some remains at the centromere until anaphase Meiosis - Loads along homologous pairs in meiosis 1 - Exists only between centromeres of sister chromatids in meiosis 2 similar to mitosis

Answer 21

They cause the chromatin to condense at the beginning of mitosis CDK protein triggers M phase and causes condensin to accumulate

Answer 22

Euchromatin is less densely packed, more transcriptionally active and appears lighter than heterochromatin in G-banding

Answer 23

It is a way to visualize chromosomes. Trypsin partially digests histones and allows dye to bind to DNA so that they can be visualized. Each chromosome has a fairly standardized pattern of bands that allow geneticists to identify them. Each band is made up of 50-100 genes.

Answer 24

During prometaphase. The chromosomes can be visualized then or during metaphase but the bands are clearer during prometaphase than metaphase

Answer 25

A repetitive sequence of DNA on each chromosome that allows the proteins of the mitotic spindle to bind during mitosis.

Answer 26

1 meta centric: centromere basically in the center 2 Submetacentric: centromere halfway between the center and one end 3 Afrocentric: centromere is near the end

Answer 27

The centromere divides the chromosome into 2 arms. The smaller arm is the p arm (petite) and the q arm is the larger arm

Answer 28

Telomeres are repeats of a 6 base pair sequence (TTAGGG) that occur over and over near the end of the chromosome. They protect the coding regions of the chromosome from degradation since some DNA is lost in each cell cycle. Short telomeres trigger apoptosis. Telomerase is a protein that replaces telomeres and is active in germ cells but normally becomes inactive afterwards. Active telomerase is a trait of neoplastic (cancer) cells

Answer 29

Numerical: wrong number of chromosomes Structural: changes to the structure of a given chromosome Mosaicism: 2 or more genetically distinct cell lines within the same individual

Answer 30

46,xx | 47,xy,+21

Answer 31

Polyploidy involves the wrong number of copies of all chromosomes ie triploidy or 69 (n =3) while aneuploidy refers to an incorrect number of only some of the chromosomes but not all of them (most often just one) polyploidy occurs in 1% of all conceptions accounting for 10-20% of chromosomally abnormal miscarriages but is basically always lethal. Aneuploidy usually results in spontaneous abortion but in some cases can result in a live birth usually with serious defects

Answer 32

16 is the most common but basically always lethal | Trisomies 21, 18, and 13 can all result in live births as well as monosomy X or XXY

Answer 33

1 Non homologous recombination 2 double strand breaks of sister chromatids 3 telomere instability

Answer 34

An exchange of info between non homologous chromosomes A reciprocal translocation occurs when 2 non-homologous chromosomes essentially undergo crossing over A Robertsonian translocation occurs when 2 Acrocentric chromosomes join at the centromere resulting in one large chromosome that is a combination of the other two and the loss of the small p arms of both chromosomes

Answer 35

``` Down Syndrome Mild to moderate intellectual disability Characteristic facial appearance hypotonia (weak muscle tone) at birth Higher risk of: Gastroesophageal reflux Celiac disease Hypothyroidism Hearing/vision problems Leukemia Alzheimer’s ```

Answer 36

Edward Syndrome Slow intrauterine growth/low birth weight Heart defects Small abnormally shaped head Small jaw and mouth Clenched fist with overlapping fingers Most die within a month and those that don’t usually have severe intellectual disabilities

Answer 37

Patau Syndrome Severe intellectual disabilities Many physical abnormalities especially along the midline: cleft lip/palate, micropthalmia (small underdeveloped eyes), extra fingers, toes Heart and spinal chord defects

Answer 38

Monosomy X Results in female sex characteristics Short stature Early loss of ovarian function and infertility Most do not undergo puberty without hormone treatment 30% have extra skin folds on the back of the neck 1/3 coarctation (unusually narrow) of the aorta

Answer 39

XXY karyotype Male sex characteristics Taller than average Infertile small testes —> low testosterone —> delayed puberty Can develop some feminine feature such as breasts, feminine belly fat placement patterns, hip structure, etc.

Answer 40

Nondisjunction during Meiosis 1 of oogenesis

Answer 41

1 Reverse transcriptase - goes backward from RNA to protein | 2 RNA as the final product- tRNA, miRNA, snRNA, rRNA are not meant to be translated into protein

Answer 42

1 DNA/gene loss 2 DNA/Gene amplification 3 DNA rearragement- Ex: immunoglobulin subunits can be rearranged to create many unique proteins

Answer 43

1 Globin gene is methylated in all cells besides red blood cells 2 X-inactivation 3 Imprinting

Answer 44

CpG islands or regions with a high number of C’s followed by G’s. The reason is because C’s are generally methylated and this sequence is a palindrome that allows both strands to be methylated

Answer 45

Each division there one strand comes from the parent cell and one new strand. The parent strand if it was methylated will remain methylated and the new strand is not methylated. This is referred to as hemimethylated. All hemimethylated cells are recognized and methylated.

Answer 46

1 All DNA is deleted from mature RBC’s stopping expression entirely 2 Globin gene is methylated in all cells except red blood cells to keep it from being expressed 3 As RBC’s mature, the chromatin becomes more condensed limiting expression 4 When iron is not present, Globin mRNA’s are prevented from being translated since they will not be able to form hemoglobin

Answer 47

``` Ricin: E Kanamycin P Tetracycline P Puromycin B Cycloheximide E Streptomycin P Gentamicin P Neomycin P Diphtheria toxin E Erythromycin P Chloramphenicol P Rifamycin P Alpha amantin E Actinomycin D B ```

Answer 48

Loss of function refers to a mutation which reduces or eliminates the function of a protein. These disorders are generally recessive since one functional copy is often enough to prevent a disorder. An example of this is Duchenne muscular dystrophy. However in the case of proteins that are required in high quantities, loss of function disorders may be dominant as is the case for osteogenesis imperfecta Gain of function mutations are when the mutation causes the protein to have a function that the normal protein did not have either within the same pathway as is the case in achondroplasia or in an unrelated pathway as is the case in Huntington’s disease. These disorders are generally dominant with the main exception being sickle cell anemia.

Answer 49

Group of disorders characterized by brittle bones Type 1 = milder leads to frequent fractures of long bones with any exertion which heal normally Type 2 = more severe, many fractures present at birth and patients normally die within a few weeks of birth

Answer 50

This is caused by a reduction in the amount of collagen which is important in bone formation Collagen is made up of 2 Alpha 1 chains and 1 Alpha 2 chain Type 1 - mutation results in no production of alpha 1 —> heterozygotes produce 1/2 normal alpha 1 and therefore 1/2 normal collagen Type 2 - point mutation to alpha 1 chain that makes any collagen chain with defective alpha 1 chain non-functional. This leads to 3/4 of collagen becoming non-functional and only 1/4 of the normal amount of collagen

Answer 51

1 Novel mutations and mosaicism/chimerism, a novel mutation could occur which is only present in some fo the cells which could make it so that the phenotype is not present but if the mutation is present in any germline cells, it could be passed on. 2 For recessive disorders, carriers could be at an advantage in some ways such as sickle cell

Answer 52

Both result in different genetic cell lines within the same organism but the mechanism is different. Mosaicism: Mutation occurs early in cell divisions of the embryo. The earlier the mutation occurs, the more cells will be affected Chimerism: two genetically distinct zygotes fuse to form one organism early in cell division. Often as a result of one zygote holding a fatal abnormality that would otherwise cause spontaneous abortion

Answer 53

Autosomal dominant Gain of function mutation to the fibroblast growth factor receptor (FGFR3) gene. Mutation leads to ligand independent stabilization of dimers activating downstream signaling. Results in lack of normal growth in long bones but otherwise healthy individuals. 80-90% are de novo mutations

Answer 54

A genetic disease that occurs earlier and more severely in each successive generation. This is explained by triplet repeat expansion where a disease is caused by an abnormally high number of repeats of a 3 nucleotide sequence. The number of repeats generally increases each generation and the higher number of repeats the more sever the disorder.

Answer 55

Autosomally dominant gain of function disease caused by expansion of the number of CAG repeats in a specific gene. Normal is 10-30 repeats Affected is 36+ Average onset is 37 years with 100% penetrance by age 80 Begins with mild motor function deficiencies memory loss and progresses to uncontrollable movements, extreme personality changes, severe memory loss and severe psychiatric conditions until the patient is immobilized and cognitively non functional. Death 10-20 years after onset.

Answer 56

Autosomal recessive loss of function mutation to Survival motor neuron 1 (SMN). Leads to motor neuron degeneration the severity of which is dependent on the number of copies of SMN2 that an individual has. Type 1: born with little muscle tone - death within 2 years Type 2: sits but never stands childhood lethal Type 3 and 4: most mild with some adult survival but generally loss significant mobility Recent gene therapy has been successful to date in treating SMA

Answer 57

X-linked recessive disorder Delayed motor development, proximal muscle weakness, classic microscopic myopathy can changes, muscle fiber breakdown results in high serum levels of muscle enzymes such as creatine kinase, dilated cardiomyopathy, wheelchair bound by 12, typically die by late 20’s

Answer 58

Allelic: same phenotype caused by different mutations to the same gene Locus: Same phenotype caused by mutations to different genes often within the same pathway Clinical: Very different phenotypes resulting from mutations in the same gene

Answer 59

Similar to X-linked dominant transmission, variability in symptoms based on mixed population of normal and affected mitochondria Mostly affect aerobic tissues (nervous system, eyes, cardiac and skeletal muscle)

Answer 60

A chemical is added to cells to arrest them in metaphase and cells are dyed and dropped onto a microscope slide so that chromosomes and banding patterns can be analyzed. Used for- detection large chromosomal abnormalities such as aneuploidy, translocations, deletions, duplications etc. Can’t be used for Uniparental disomy, methylation changes or abnormalities smaller than 5Mbps

Answer 61

Fluorescent probes are created to be complimentary to certain DNA regions. They are then hybridized to the cellular DNA and visualized. Can tell: Deletions, duplications, translocations and mosaicism (limited by size of probes and knowledge of the target) Can’t tell: Uniparental disomy or methylation changes

Answer 62

Oligonucleotide probes are placed on a glass slide. Patient and control DNA are labeled with different colors and then allowed to hybridized with probes. The fluorescent patterns are then compared. Can tell: deletions and duplications Can’t tell: Balanced rearrangements, UDP, Anything smaller than 10-30Kbps, changes in methylation

Answer 63

Microsatellite PCR targets short repeats that occur a different number of times for different people. Can be used for: Crime scene identification, paternity testing, changes in methylation and UDP

Answer 64

It is like PCR but it also includes labeled dideoxyribonucleotides which terminate the chain and be used to tell which base is present at each location. Can tell: Small alterations in targeted regions Can’t tell: UDP or methylation (clinically )

Answer 65

Nucleotide probes are fused to universal PCR primers and hybridized with DNA. Then PCR is performed which amplifies only those probes that hybridized. Can tell: Small deletions and duplications no larger than one gene Can’t tell: Single base mutations, UDP, methylation, translocations and inversions

Answer 66

The genome is fragmented and bound to adapters then ligated to a flow cell. Bridge amplification is used to create clusters of identical DNA strands. Fluorescently tagged reversibly terminating nucleotides are added and lasers are used to tell what base was added at each location. They are then removed and cycled through for each location until a sequence is created. This can sequence much more information including a whole exime at a much lower cost than Sanger sequencing but is more error prone. Can be used to find small abnormalities and could eventually be used to look for larger ones.

Answer 67

Hemoglobin is a tetramer and myoglobin is a tetramer this causes hemoglobin to exhibit cooperativity and have a lower oxygen affinity in the tissues than myoglobin. Because of this difference, hemoglobin is used to transport oxygen throughout the body and myoglobin is used to store oxygen to be used during exercise in skeletal muscles

Answer 68

In the deoxygenated state, the iron atom of hemoglobin is pulled out of the plane of the heme ring and when oxygen binds it pulls the whole helix to which iron is bound so that the iron is back in the plane. This difference is characterized as the T-state (deoxygenated) and the R-state (oxygenated).

Answer 69

Several ionic interactions between amino acids that stabilize alpha-alpha and alpha1-beta2 and alpha2-beta1 subunit interactions in the T-state are no longer possible in the R state due to the conformational changes that take place

Answer 70

CO binds at the oxygen binding site with 300 times more affinity than oxygen blocking O2 from binding. CO is constantly present in small amounts in the body but Hb bound CO is removed in a matter of hours

Answer 71

The T-state of hemoglobin has a lower affinity for oxygen than the R-state. When 2 oxygen molecules are bound to a Hb the two states are in equilibrium. However when 1 O2 is bound the T-state becomes favored and when 3 are bound the R state is favored. This increases the affinity for oxygen in high concentrations of O2 and decreases affinity for O2 at low concentrations

Answer 72

All three lower the affinity for oxygen by favoring the T-state 1pH- low pH causes H+ ions to bind to hemoglobin favoring the T-state. Low pH results from exercise 2 2,3BPG- occurs as a short term result of high altitude 3 CO2 - also occurs as a result of exercise

Answer 73

Hemoglobin A is the major type present in adults consisting of two alpha and two beta subunits Hemoglobin A2 is present in smaller concentrations in adults and is made up of 2 alpha and 2 delta subunits Hemoglobin F is found in fetuses and consists of 2 alpha and 2 gamma subunits Embryonic hemoglobin consists of 2 alpha and 2 epsilon subunits Pre-embryonic hemoglobin consists of 2 zeta and two epsilon subunits Fetal and embryonic hemoglobin variants have higher O2 affinity than adult hemoglobin

Answer 74

Any mutation to the alpha subunit of hemoglobin which causes insufficient production of hemoglobin Most are deletions 1 deletion = silent carrier w/o symptoms 2 deletions = alpha thalassemia trait and mild anemia 3 deletions = hemoglobin H disease- moderate to marked anemia but not lethal 4 deletions = hemoglobin Bart’s no O2 carrying capacity, neonatal death

Answer 75

Any of over 100 mutations to the beta subunit of hemoglobin which causes insufficient hemoglobin production Clinically heterogenous From mild to major (Cooley’s) Cooley’s = transfusion dependent, infants are listless and pale, grow slowly and may be jaundiced, internal organs can be enlarged

Answer 76

Results from point mutations in the hydrophobic center of the hemoglobin usually in the beta subunit Results in desaturation of the molecule and coagulation within the erythrocytes (Heinz bodies)

Answer 77

Results from a single point mutation causing an amino acid change from glutamate to valine in beta subunit of hemoglobin that causes them to become “sticky” in T state resulting in sickle shaped RBC’s

Answer 78

The step before a mature RBC in Erythropoiesis. You can often see them on blood smears they will appear larger than erythrocytes and purple with a mesh-like network of rRNA. They normally make up about 1% of RBC’s

Answer 79

They can be measured in a complete blood count. They are useful to understand the rate of Erythropoiesis

Answer 80

Higher: blood loss or hemolytic anemias Lower: vitamin deficiency or Myelodysplastic syndromes

Answer 81

Biconcave discs with central pallor 1/3 of diameter- this increases the surface area for gas exchange Unique membrane and cytoskeleton allow for flexibility and deform ability which is important for fitting through blood vessels No nucleus

Answer 82

Fragmented RBC’s that look like triangles or helmets. Are caused by shearing or mechanical force Only present under severe pathological conditions such as artificial heart valves or microangiopathic hemolytic anemia, malignant hypertension

Answer 83

They are crescent shaped with pointed ends. Typical lifespan is 10-20 days

Answer 84

RBC’s shaped like spheres with no central pallor due to loss of membrane. This causes decreased surface area to volume ratio. Can result from pathology such as burns and autoimmune hemolytic anemia or it can be hereditary

Answer 85

An autosomal dominant gene usually affecting the cytoskeleton protein ANK1 (ankyrin)

Answer 86

Abnormal RBC’s with too much membrane increasing the surface area to volume ratio to higher than normal. THey are seen in liver disease and after removal of the spleen and sometimes in thalassemia

Answer 87

They are elongated oval shaped RBC’s. They look kind of like sickle cells but with rounded edges. They are most commonly seen in iron and vitamin B12 deficiencies as well as hereditary ovalocytosis

Answer 88

Autosomal dominant gene in the cytoskeleton protein spectrum

Answer 89

RBC’s with small blue dots dispersed throughout which are caused by clusters of rRNA OFten seen in lead and arsenic poisoning, alcoholism and thalassemia

Answer 90

All of the information necessary for proper folding is inherent in the primary structure and there is no energy necessary for them to properly fold

Answer 91

There is not enough time for proteins to try every conformation and choose the best one. This leads to the idea that there is a predetermined pathway

Answer 92

Interactions of amino acids with other proteins toward aggregation competes with proper folding. When folding takes place in a crowded environment there are many other proteins around with which the protein may aggregate

Answer 93

In a crowded cell, a small molecule could fit into essentially any part of the open space. However larger molecules require a larger space which excludes much of the open space because. This makes the protein act as though the concentration was higher than it actually is (effective concentration vs actual concentration).

Answer 94

New, unfolded proteins Mutated proteins Nuclear proteins Proteins that become unfolded as a result of stress conditions

Answer 95

Helper proteins such as chaperones which protect the unfolded protein from unwanted interactions and allow it to fold properly

Answer 96

It catalyze the inter conversion of cis and trans isomers of proline peptide bonds allowing for better protein folding

Answer 97

IT catalyze disulfide bond formation

Answer 98

Small heat shock proteins- very small, ATP independent aid in the formation of oligomeric complexes Low MW - relatively small, ATP dependent, bind to hydrophobic regions until they can properly fold High MW- large proteins, ATP dependent, form a cage-like structure around the protein preventing it from interacting with anything else and allowing it to fold

Answer 99

Loss of function and gain of function Cystic fibrosis is an example of loss of function because the disease is caused by misfolded and ineffective CFTR protein Systemic amyloidosis is an example of gain of function because proteins that wouldn’t normally aggregate do forming plaques that damage tissues

Answer 100

Normally, alpha-1 antitrypsin coats and protects the lungs from damage. However the misfolded protein does not fulfill this role and leaves the lungs to be damaged (loss of function) in addition, misfolded protein accumulates in the liver causing liver damage (gain of function)

Answer 101

It is a dye that is used to diagnose systemic amyloidosis. It turns fluorescent green when positive for amyloidosis

Answer 102

Cross Beta sheets

Answer 103

Primary- the most common, caused by overexpression of light chain immunoglobulin which aggregates Secondary occurs as a result of chronic inflammation Familial is hereditary based on a mutation to the TTR protein

Answer 104

Misfolded proteins which when in contact with properly folded versions of that protein act as a template for the properly folded protein to take on the misfolded form. Thus they are like protein infections

Answer 105

Both are used by cells to promote proper folding of proteins under crowded conditions. Foldases actively catalyze reactions related to folding while chaperones similar protect the protein from interacting with other proteins to allow it to fold by itself

Answer 106

About 6000 Mbps

Answer 107

In repeated DNA elements

Answer 108

Circular similar to bacteria, contains about 37 genes 5-10 copies of genome per mitochondrion

Answer 109

A SNP is relatively common, occurring in at least 1% of the population while mutations are more rare

Answer 110

Deletions or duplications of sections of DNA of 1kb to 1Mb in size. They are important in the normal function of special senses and play a role in diseases such as cancer, autism, schizophrenia

Answer 111

A specific pattern of nucleotides repeated over and over right next to each other. They occur mostly in non-coding regions 1 satellite DNA 2 mini satellite DNA 3 microsatellite DNA

Answer 112

Alpha-satellites = centromeres | Beta satellites - variable regions on acrocentric chromosomes. They occur near the centromeres

Answer 113

All are tandem repeats and they are different classifications based on size Satellites are larger than 100bp Mini satellites are 10-100 bp Microsatellite are 2-4 bp

Answer 114

Minisatellites because they are. 6 bp repeats

Answer 115

They are hotspots for recombination and replication errors because of their similarity

Answer 116

A mutation that occurs in the 2bp before or after an exon that determines splicing. These are almost always harmful

Answer 117

``` P.Val58* C.397delAG (p.Gly47Ilefs*80) C.A786C G.G987T P.Val430Leu G.746+G>T G.754-T>C ```

Answer 118

Exogenous occurs when the damaging factors comes from without the cell while endogenous is when the damaging factor comes from within the cell

Answer 119

1 UV- irradiation- tends to cause thymine dimers which are repaired by nucleotide excision repair 2 Alkylating agents- tend to affect guanine residues and may add small or large chains that can distort the helix and cross link strands. Alkylating agents tend to cause cancer

Answer 120

Adeline’s and guanine are often spontaneously lost during replication. This is one major cause of mosaicism

Answer 121

An amine group is lost from cytosine turning it into uracil. Because uracil bonds with adenine, the base is changed in the next replication. This is a common cause of endogenous DNA mutations

Answer 122

They add carbonyls onto guanine which makes it as likely to pair with adenine as with cytosine which then results in DNA mutations during replication 8 oxo guanine

Answer 123

1 Slippages occur during microsatellites leading to deletions or duplications of genes 2 Tandem repeats can lead to unequal crossing over in meiosis leading to deletions and duplications of major portions of DNA

Answer 124

When 50% of a protein is not enough to be functional. This causes heterozygous individuals with a null mutation to have a disease phenotype

Answer 125

A mutant protein that loses its normal function and also interferes with the normal protein product such as through competitive inhibition in transcription factors and multimeric proteins

Answer 126

Purine loss and 8-oxo-guanine

Answer 127

It is involved in 8-oxo-guanine DNA repair mutations cause a recessive phenotype leading to many colon polyps and increased risk for colorectal cancer called MUTYH associated polyposis

Answer 128

Repairs bulky DNA lesions such as thymine dimers. Mutations to machinery lead to recessive phenotypes increasing sensitivity to the sun and risk of skin cancer

Answer 129

MLH1, MSH2, MSH6, and PMS2 | MLH1 and PMS2 dimerize as do MSH6 and MSH2

Answer 130

1 Maintenance of structure and integrity of DNA - BLM (helicase) - Bloom Syndrome (recessive) 2 Signal the repair process - ATM - ataxia telangiectasia 3 Locate damage and trigger repair- FANC genes - Fanconi anemia 4 Repair of DNA - BRCA1 and BRCA2- Hereditary breast and ovarian cancer (dominant) 5 End joining of dsDNA - NBN, Rad50 and MRE11A - Nijmegen breakage syndrome

Answer 131

PARP 1 is involved in single stranded DNA repair and BRCA1 and 2 are related to double stranded repair. These processes have some overlap and if both are compromised, cell death is triggered. Cancers where BRCA1 or 2 is mutated would then trigger cell death if PARP1 is compromised

Answer 132

Nucleosides do not contain phosphate groups

Answer 133

Purines: 2 Pyrimidines: 1

Answer 134

De novo synthesis of nucleotides

Answer 135

Glucose 6 phosphate from glycolysis is converted to Ribose 5 phosphate by the reduction of 2 NADP to NADPH. Then Ribose 5-phosphate is converted to 5 Phosphoribosyl-1-pyrophosphate PRPP which is important in nucleotide synthesis. NADPH is also an important antioxidant. The rate limiting enzyme is glucose 6 phosphate dehydrogenase

Answer 136

Results in hemolytic anemia in response to infection, certain drugs and fava beans which all increase levels of reactive oxygen species. this occurs because glucose 6 phosphate dehydrogenase catalyzes the rate limiting step of the pentose phosphate pathway which produces NADPH an important antioxidant X-linked recessive

Answer 137

Ribose 5P—> PRPP—> 10 steps —> IMP—> 2 steps—> AMP or GMP Key enzyme: glutamine PRPP aminotransferase Important substrates: Amino acids (glutamine x2, glycine, aspartate), Carbon sources (HCO3- and THF)

Answer 138

AMP-> Adenosine->Inosine->Hypoxanthine->Xanthine->Uriel acid Key enzymes: Adenosine deaminase - catalyzes adenosine to inosine Xanthine oxidase- catalyzes hypoxanthine to Xanthine and Xanthine to Uric acid

Answer 139

GMP->Guanosine->Guanine->Xanthine->Uric acid | Key enzyme Xanthine oxidase- catalyzes Xanthine to Uric acid

Answer 140

Severe combined immunodeficiency called (scid) occurs because ADA leads to the buildup of ATP which inhibits RNR which catalyzes dNTPS. Without dNTP’s cells can’t divide and this kills T lymphocytes and B lymphocytes which constantly divide

Answer 141

Gout occurs when Uric acid builds up and forms crystals leading to chronic inflammatory arthritis. This occurs as a result overactivity of purine catabolism. It can be treated with allopurinol which resembles hypoxanthine and inhibits Xanthine oxidase lowering the production of Uric acid

Answer 142

Minor Adenine + PRPP-> AMP + ppi Enzyme: Adenine phosphoribosyltransferase APRT Major Hypoxanthine + PRPP->IMP +PPI->AMP or GMP Guanine+PRPP->GMP+ppi Enzyme: Hypoxanthine-guanine phosphoribosyltransferase HPRT

Answer 143

Lesch Nyhan syndrome- severe hyperuricemia and compulsive self-mutilation. This occurs because HPRT salvages purines and if they are not salvaged they will produce Uric acid in over abundance and create hyperuricemia

Answer 144

Conversion of PRPP to 5-phosphoribosyl amine (2nd step)

Answer 145

Substrates: amino acids (glutamine and aspartate) and Carbon sources: CO2 and THF Key enzyme: carbamoyl phosphate syntheses II

Answer 146

Production of carbamoyl phosphate by carbamoyl phosphate synthetase II (CPSII)

Answer 147

CO2+Glutamine + ATP->4 Steps-> +PRPP-> 2 steps-> UMP->UDP->UTP->CTP->dCTP

Answer 148

CO2 + Glutamine +ATP->4 Steps->+PRPP-> 2 Steps-> UMP-> dUMP-> dTMP methylene tetrahydrofolate (THF) is required for final step

Answer 149

Cytidine + ATP -> CMP +ADP

Answer 150

Cytidine and uridine -> alanine Thymidine-> amino butyrate Their rings are no longer intact making them water soluble so they don’t cause disorders unlike uric acid the product of purine biosynthesis.

Answer 151

Symptoms: megaloblastic anemia, crystalline sediment of orotic acid in urine, slow growth Caused by a deficiency in UMP synthetase which prevents biosynthesis of Pyrimidines. Lack of Pyrimidines leads to the above symptoms

Answer 152

In pyrimidine biosynthesis, heterocyclic rings are synthesized first and then bound to ribose phosphate. The opposite is true in purine biosynthesis.

Answer 153

All other Pyrimidines are converted to deoxyribonucleotides from their corresponding ribonucleotide. However, thymine is converted from deoxyribouracil.

Answer 154

Ribonucleotide reductase

Answer 155

ATP activates it and dATP inhibits it. This relates to SCID in which adenosine deaminase is deficient leading to accumulation of dATP’s which inhibit ribonucleotide reductase preventing the production of dNTPs

Answer 156

Folate is a B-vitamin that plays an important role in nucleotide synthesis by being a carbon source. It’s active form is tetrahydrofolate (THF) it is converted from folate by successive reductions with NADPH by the enzyme dihydrofolate reductase

Answer 157

All function in some way by inhibitting pyrimidine biosynthesis preventing the production of nucleotides needed for replication 5-fluorouracil is a structural analog of thymine and blocks the conversion of dUMP to dTMP Methotrexate is a structural analog of folate and competitively inhibits dihydrofolate reductase preventing the formation of THF which is necessary for nucleotide synthesis including conversion of dUMP to dTMP Hydroxyurea inhibits ribonucleotide reductase preventing the formation of deoxyribonucleotides from their corresponding ribonucleotides

Answer 158

It is found near the N-terminus and is made up of hydrophobic amino acids

Answer 159

It is found near the N-terminus and contains regularly distributed basic (Positively charged) amino acids

Answer 160

Import: Short and made up of positively charged amino acids Export: short and made up of hydrophobic amino acids

Answer 161

It signals that a protein is to be maintained within the lumen of the ER rather than to be transported to another organelle. It is 4 amino acids at the C terminus with varying characteristics

Answer 162

In paternal imprinting, the father’s copy of a gene is methylated and turned off. IN maternal imprinting it is the mother’s copy that it methylated and turned off

Answer 163

Transferrin gene is constantly transcribed but its mRNA is degraded and not translated unless iron is low in which case it is immediately translated. Allows the body to react immediately to low iron

Answer 164

They regulate splicing

Answer 165

A rare form of anemia caused by failure of the bone marrow to produce all blood cell types

Answer 166

80 to 90% are de novo mutations and all de novo mutations come from the father

Answer 167

Spinrata-causes inclusión of exon 7 to be more likely in smn2. Zolgensma delivers the smn1 gene in adeno associated virus

Answer 168

It states that a genetically inherited disease causing death before eproduction should decrease by 1/3 each generation. This shows us that 1/3 of Duchenne muscular dystrophy cases are de novo mutations because the frequency is remaining constant

Answer 169

A specific form of mosaicism that results from differences in the number of normal and abnormal mitochondria within each cell

Answer 170

30nm fiber

Answer 171

1 Fertilization of ovum by 2 sperm | 2 an error in meiosis 2 of oogenesis

Answer 172

The father

Answer 173

They may be phenotypically normal if they have a full compliment of genetic material but have problems with reproduction because of difficulties of lining up chromosomes in meiosis

Answer 174

47,XXX and 47,XXY- these usually show no significant physical phenotype and only a mild learning disability

Answer 175

Lack of a paternally inherited X chromosome

Answer 176

A sac of fluid that forms during development near the back of the neck associated with Turner’s syndrome

Answer 177

Caused by a deletion on chromosome 7 Symptoms: delayed speech and development, unique face, mild to moderate mental retardation, feeding issues, and cocktail personality

Answer 178

Any of them that use probes or primers such as PCR, Sanger sequencing and multiple probe ligations MLPA

Answer 179

In the bone marrow, specifically the medullary space of long bones and especially in the hip

Answer 180

A hormone that is released in response to low levels of oxygen and causes increased erythropoiesis

Answer 181

Production of red blood cells occurring outside of the bone marrow. Most often in the liver, spleen and lymph nodes. Occurs normally in embryos but in adults it is a sign of RBC turnover or bone marrow failure. It is also associated with hereditary spherocytosis

Answer 182

They get smaller, more hemoglobin and more chromatin condensation with each step

Answer 183

A holoprotein is a protein that contains at least one non-protein prosthetic group. The heme group is a non-protein prosthetic group

Answer 184

It is a porphyrin ring with 4 nitrogen containing rings each of with interacts with Fe which is at the center

Answer 185

Alpha hélices

Answer 186

The effect of low pH on hemoglobin binding curve. Namely, at low pH protons bind to hemoglobin stabilizing the T state and dramatically lowering the affinity for oxygen

Answer 187

The various hemoglobin genes are arranged so that the genes for like subunits are grouped together. Chromosome 16 contains 1 zeta gene and 2 alpha genes close to each other Chromosome 11 contains 1 delta, 1 epsilon, 2 gamma and 1 beta gene all close together

Answer 188

The one that raises affinity

Answer 189

Caused by a mutation at the exact same locus as sickle cell disease that changes to a positively charged amino acid instead of a hydrophobic amino acid (like in sickle cell). It is homozygous recessive and causes a milder anemia than sickle cell. Individuals who are heterozygous for the hemoglobin C allele and sickle cell allele have sickle cell anemia but it is usually milder than those who have homozygous for sickle cell trait

Answer 190

Abnormal protein concentration and protein infections

Answer 191

``` Primary = AL Secondary = A Familial = ATTR ```

Answer 192

Synonymous do not cause amino acid changes while non-synonymous do

Answer 193

``` Minisatellite = variable number tandem repeat Microsatellite = short tandem repeat ```

Answer 194

An individual who has inherited two partially functional genes. Phenotype depends on the severity of the reduced function of each gene. An example would be someone who inherited one sickle cell allele and one hemoglobin C allele. In this case they would display a phenotype more severe than homozygous for hemoglobin C but less severe than homozygous for sickle cell

Answer 195

It fixes replication errors, mismatched nucleotides, and problems with microsatellites

Answer 196

Thymidine synthetase

Answer 197

1 Receiving information 2 Import and export 3 Movement and change of shape

Answer 198

Describes the way the membrane acts which is like a fluid in 2 dimensions

Answer 199

The major component is phospholipids which contain a hydrophilic head and 2 hydrophobic tails. These form a lipid bilayer with hydrophilic heads on the outside and hydrophobic tails in the center. Another major part of membranes are proteins. Cholesterol is present inside of the membrane and fills in the gaps between hydrophobic tails as well as making the membrane less permeable. Finally sugars are found on the outside of the membrane covalently attached to either proteins or lipids.

Answer 200

A hydrophilic head attached to phosphate which is attached to a glycerol molecule with 2 hydrophobic tails coming off of it. On one of the fatty acid tails, a cis double bond causes a kink

Answer 201

Amphipathic means having both a hydrophobic and hydrophillic region in the same molecule. Proteins and lipids in the membrane are amphipathic allowing them to form a bilayer

Answer 202

1 Phosphatidyl ethanolimine 2 Phosphatidylserine 3 Phosphatidylcholine 4 Sphingomyelin 1-3 are exactly the same other than the hydrophilic head group which is reflected in their name. Phosphatidyl serine is - charged while the rest are neutral 4 has a choline head group but is attached to the hydrophobic portion by a different molecule other than glycerol 5 (minor) Phosphatidyl inositol- important for recruiting signaling molecules

Answer 203

They move freely in: lateral diffusion (side to side), flexión (movement of tails), and rotation (spinning in place) Flip flop or changing from one side of the bilayer to the other is rare and requires flipase or flopase enzymes. This type of movement is important in membrane synthesis

Answer 204

There are differences between the outer and inner layers of the bilayer. Mainly glycolipids and proteins are found only on the outer layer and the inner layer is more negatively charged due to the presence of Phosphatidyl serine and Phosphatidyl inositol

Answer 205

Will: hydrophobic molecules small or large such as O2 or steroids Rarely will: Very small hydrophilic molecules Won’t: large hydrophilic molecules or charged molecules of any size

Answer 206

Regions of the membrane with distinctive structure and function. They contain a lot of cholesterol and glycosphingolipids which makes them thicker and less fluid and this determines what proteins will be present here. They are often involved in cell signaling

Answer 207

1 Integral- directly attached to the membrane and require detergents to be separated A Transmembrane- passes through the entire membrane B Membrane associated C lipid linked - B and C are covalently bound to membrane components 2 Peripheral- interact non-covalently with membrane proteins and can be separated without detergent A Protein attached

Answer 208

1 Transporters 2 Anchors 3 Receptors 4 Enzymes

Answer 209

They are amphipathic with regions of hydrophobicity which pass through the center of membranes and hydrophilic regions that remain on the outside of the bilayer

Answer 210

They often form alpha helices in their hydrophobic regions which allow them to show hydrophobic amino acids on the outside of the helix. Sometimes multiple amphipathic alpha helices will combine together to form a hydrophilic pore where hydrophilic molecules can pass through the membrane Less often, beta sheets can be found which can form beta barrels which appear barrel like and function similarly to hydrophilic pores formed by alpha helices

Answer 211

1 They can be bound to cytosolic proteins 2 they can be bound to extracellular proteins 3 they can be bound to proteins on other cells 4 The cell can form barriers to diffusion

Answer 212

A framework of fibrous proteins that links proteins in the membrane together to strengthen the otherwise weak membrane

Answer 213

Glycoproteins are proteins linked to sugars that are common in the outer side of the plasma membrane. Proteoglycans are a specific kind of glycoprotein that is heavily glycosylated with long, repeating, unbranched amino containing sugars unlike the shorter non-repeating and branched sugars on most glycoproteins. Proteoglycans are especially important in forming the extracellular matrix and connective tissues

Answer 214

The layer of sugars on the outside of the plasma membrane made up of glycolipids and glycoproteins. It functions to protect the membrane from mechanical damage, cell-cell signaling and lubrication of extracellular space in vascular system

Answer 215

Energy: X-rays How it shows differences: different electron densities Benefits: Fast, great resolution Limitations: Poor tissue contrast, uses radiation

Answer 216

Energy: X-rays HOw it shows differences: Different attenuation of x-rays relative to water Benefits: Very good contrast at all tissue densities Limitations: TOns of radiation

Answer 217

Energy: Radio waves How it shows differences: different rates of nuclear relaxation Benefits: Best tissue contrast, no radiation Limitations: Slow and expensive, magnet dangers

Answer 218

Energy: Sound waves How it shows difference: Different acoustic impedance Benefits: Real time imaging, no radiation Limitations: User dependent, many artifacts

Answer 219

Energy: Gamma rays How it shows difference: different levels of radioactivity Benefits: See physiology and pathophysiology in action Limitations: Worst resolution, Radiation

Answer 220

Diffusion always refers to passive movement of molecules down their concentration gradient. In simple diffusion they cross the membrane directly- this is only possible for small, hydrophobic molecules. In protein assisted diffusion, proteins embedded in the membrane allow movement of larger or hydrogphilic compounds

Answer 221

Flux is the amount of molecules crossing a membrane at any given time. Molecules are always crossing in both directions so net flux is the difference between the two one-way fluxes

Answer 222

It explains how much of a given molecule will diffuse across a membrane. Diffusion is directly proportional to: K- permeability of solute A- Surface area of membrane C = solute concentration gradient Diffusion is inversely proportional to : delta x - distance the solute must travel

Answer 223

Lipid solubility- directly proportional | Solute size- indirectly proportional

Answer 224

Ion channels | Facilitated diffusion

Answer 225

They both function on passive diffusion that is they do not require energy and transport only in the direction of the concentration gradient. Ion channels simply work by creating a very small pore in the membrane that will allow ions through, they work very quickly, can only transport ions and use size and charge of amino acids within the pore to select solutes. Facilitated diffusion works by binding the solute at a specific site causing a conformational change which allows the solute to be released within the cell, they work much slower, they can transport ions or larger molecules, and they select based on the specific molecule’s ability to bind at the active site.

Answer 226

1 Ligand gated - activated by binding of a signaling agent 2 Voltage gated- activated by changes in membrane potential 3 Mechanically gated- activated by physical deformation of the surrounding membrane

Answer 227

Diffusion of ions depends not only on the concentrations of that specific ion but also concentrations of charge on either side of the membrane

Answer 228

Membrane potential is the difference in charge on either side of the membrane. Generally, cells have more negative charge inside than out (-70mv)

Answer 229

Primary- uses ATP for energy | Secondary uses ion gradient for energy

Answer 230

Solute binds to pump protein-> ATP is hydrolyzed -> Pi binds to pump-> conformational change of pump allows solute to enter/exit the cell

Answer 231

It transports 3 sodium out of the cell and 2 potassium into the cell against their gradients with the use of 1 ATP. This makes them primary active transport

Answer 232

The usual energy source is the sodium gradient. 1 Co-transport = solute moves in the same direction as sodium 2 Counter-transport/antiport = solute moves in the opposite direction of sodium

Answer 233

It can’t unless there are channels called aquaporins which are present in different concentrations in most cells. Amount of aquaporins determines speed of osmosis.

Answer 234

Osmolarity is the concentration of all solutes Tonicity is the concentration of only non-permeable solutes Most solutes in the body function as if they were non-permeable so the two are usually very similar

Answer 235

Hypertonic- water leaves, cell shrinks Isotonic- no net movement of water, no change in cell size Hypotonic- Water enters cell, cell swells

Answer 236

Because they are quickly pumped by the sodium potassium pump to maintain their gradients.

Answer 237

It is made up of roles rolls of membrane which may be contiguous with the rough ER but does not contain ribosomes. It’s function is to synthesize fatty acids and phospholipids

Answer 238

Cells which produce a large quantity of lipids such as steroid producing cells for example the adrenal cortex or the leydig cells in the testes

Answer 239

Sarcoplasmic reticulum, it sequesters calcium ions which play an important role in the contractile impulse

Answer 240

It helps to detoxify some hydrophobic compounds turning them into water soluble compounds which can be excreted in the urine. These include toxins such as carcinogens and pesticides and drugs like ethanol and the barbiturates thiopentanal and phenobarbital

Answer 241

1 Deliver newly made molecules to destinations 2 Communicate with extracellular environment 3 Ingest extracellular particles and solutes

Answer 242

Secretory pathway- in to outmoves from the ER to the golgi and from there it can move to the plasma membrane or lysosomes Endocytic pathway - out to in Moves from outside of the cell to components within the cell

Answer 243

Budding is when the vehicle breaks off from the membrane at its origin Fusion is when the vesicle joins the membrane at its target

Answer 244

Proteins that cover the outside of vesicles during budding and will be removed prior to fusion They function to help vesicle bud off and to aid in sorting of proteins

Answer 245

It is the most important vesicle coating protein It has 3 light and 3 heavy chains that form a 3 armed spiral structure called a triskelion. When coating vesicles it creates a honeycomb like lattice structure around the outside of the forming vesicle forcing the membrane into a circular shape

Answer 246

Clathrin binds to adaptin which binds to a receptor that is specific for a type of cargo. Different forms of adaptin exist in different areas which allow different receptor/cargo pairs to enter vesicles. After budding, clathrin and adaptin are released from the vesicle but the receptor and cargo remain

Answer 247

First, Rab protein on the vesicle binds to a tethering protein on the target which pulls the vesicle closer to the membrane. Here v-Snare on the vesicle binds to T-snare on the target and the two pull each other so close together that fusion occurs

Answer 248

1 Disulfide bonds- both intrachain and interchain 2 Lipid membrane anchors are added covalently 3 Glycosylation- usually to the N-terminus of asparagine residues but occasionally also to serine or threonine

Answer 249

Dolichol protein embedded in the ER membrane holds the oligosaccharide until it will be added to the asparagine residue by the enzyme oligosaccharyl transferase

Answer 250

ER does not allow proteins that either misfolded or did not join with the proper subunits to leave the ER. This is accomplished by chaperone proteins which bind to the unfolded protein and prevent other interactions until it is properly folded. If the protein never folds properly it is held by chaperones until it is eventually exported to the cytosol for degradation

Answer 251

The mutated protein in the cystic fibrosis gene could be at least partially functional if it reached the plasma membrane but instead it is prevented by the quality control mechanisms of the ER leading to its degradation and a severe phenotype

Answer 252

The golgi is made up of several long, flattened membranes piled on top of each other kind of like a stack of pancakes. One end is called the cis face which is where vesicles enter and the other is the trans face where vesicles exit. Cargo moves by vesicles from one membrane bound layer to another throughout the golgi until reaching the trans face

Answer 253

They are sorted and oligosaccharides are added or removed

Answer 254

Constitutive secretion- occurs at all times unregulated in all cells. It carries new proteins and lipids to the plasma membrane and transports other cargo outside of the cell Regulated secretion occurs only in specialized secretory cells such as those that release hormones. In this case vesicles storing tightly packed cargo are produced and wait near the membrane until a signal is received that causes them to fuse to the membrane releasing their contents.

Answer 255

The proteins in the lysosome that degrade different types of molecules and function under the lower pH of the lysosome relative to the rest of the cell. They are highly glycosylated to allow them to withstand the low pH.

Answer 256

These proteins contain a short amino acid sequence that targets them to lysosomes. Once in the golgi, a mannose-6 phosphate is added to these proteins. In the trans face of the golgi, the mannose-6phosphate binds to mannose-6phosphate receptors in clathrin coated pits with then form vesicles bound for early or late endosomes which will mature into lysosomes

Answer 257

Diseases caused by a defected hydrolase or cofactor that functions in the lysosome to degrade a specific molecule. This causes that molecule to build up and become toxic. Babies with these diseases appear normal at birth but show symptoms very early. Life expectancy is 15 years. Most common are : Gaucher disease, Hurler syndrome and Hunter syndrome. The most severe is I-cell disease which causes is a defect in the enzyme that adds mannose-6-phosphate to hydrolases so none of them reach the lysosome.

Answer 258

1 Phagocytosis- injestion of large particles only in specialized immune cells 2 Pinocytosis- non-specific constitutive injestion of fluid and solutes that occurs in all cells 3 Receptor mediated endocytosis- very specific uptake of molecules which bind to receptors in the membrane

Answer 259

Both are occurring constantly and non-specifically and they compliment each other so that one process doesn’t significantly change the amount of membrane in a cell

Answer 260

Membrane extends projections called pseudopods out to engulf whatever large particle it is trying to injest until it covers the entire particle and brings it in

Answer 261

They first go to early endosomes near the plasma membrane. This causes most receptors to release their substrate because of the slightly acidic environment. Endosomes sort cargo and most of the cargo released from receptors ends up in the lysosomes for degradation

Answer 262

LDL cholesterol is a complex containing cholesterol surrounded in a lipid monolayer which is surrounded by an organizing protein. This allows transport of cholesterol in blood although it is hydrophobic. This entire complex binds to receptors and is endocytosed. In the early endosomes, the cargo is released from the receptor and in the lysosome, it is degraded, releasing cholesterol which diffuses out through the membrane and into the cytosol of the cell

Answer 263

Caused by a mutation in the LDL receptor that would normally allow for receptor-mediated endocytosis that causes it to be either missing or non-functional. Thus LDL doesn’t enter cells and accumulates in the blood stream which can lead to atherosclerosis and early cardiovascular disease. Patients are treated by controlling their diets and using cholesterol lowering drugs such as statins

Answer 264

This allows: 1 Signals to be regulated at each step 2 Signals to be amplified 3 Signals to be distributed to several processes at the same time

Answer 265

1 Enzyme activity- ex kinases 2 Protein-protein interactions 3 Second messenger molecules

Answer 266

Different receptors could be present on each cell that start differing cascades or the signaling pathways could be different downstream

Answer 267

Proper withdrawal is as important as signaling itself because it if is withdrawn too quickly it can’t have a large enough effect and if it is withdrawn too slowly it could have too dramatic of effects or the receptor could be downregulated as a result. Withdrawal can occur by removing the signal molecule via diffusion, degradation or endocytosis by neighboring cells or it could occur by downregulation of the receptors either by reduced synthesis or internalization

Answer 268

Myasthenia Gravis is an autoimmune disease in which antibodies are formed against acetylcholine receptors in skeletal muscle preventing reactivity to acetylcholine. Symptoms include severe fatigue, a droopy eyelid, unsteady walking and difficulty swallowing. It can be treated by acetylcholinesterase inhibitors which prevent degradation of acetylcholine and increase its concentration

Answer 269

Immediate changes could be caused by changes in protein activity for example in changing the shape of the cell. Slower long-term results take place from signals which affect gene expression because time is needed to transcribe, translate, modify and transport protein that is expressed

Answer 270

Both contain an extracellular domain which binds to the signal molecule and both contain intracellular domains which bind to proteins. The main difference is that GPCR’s pass through the membrane 7 times while RTK’s pass through only once.

Answer 271

The GPCR is bound to a trimer of G-proteins alpha, beta and gamma. The alpha is bound to a GDP but once the signal molecule is bound to the receptor, it causes the GDP to be replaced with GTP. This change causes the alpha and beta/gamma subunits to dissociate from the receptor and become active. These subunits bind to their targets to affect some change which they causes phosphorylation of the GTP back to GDP and the trimer reforms and binds to the GPCR once again.

Answer 272

They can regulate ion channel activity or regulate membrane bound enzymes such as adenylyl ciclases

Answer 273

Gi- inhibits adenylyl cyclase Gs activates adenylyl cyclase Gq activates phospholipase C

Answer 274

Pathways related to growth, proliferation, differentiation and survival. Their substrates are often growth factors. For this reason dysregulation of these pathways often results in cancers

Answer 275

Receptor tyrosine kinases

Answer 276

When the signal molecule binds to the receptor, it causes them to dimerize. Each receptor cross phosphorylates the other. The negative charge from phosphorylation attracts new proteins and a large protein complex forms around the receptor which can begin signal transduction pathways

Answer 277

Receptors that when bound to signal molecule open or close ion channels changing the electrical charge across the membrane. These are common in neural signals.

Answer 278

A small hydrophobic molecule so that it can pass through the membrane These are basically always involved in changing gene expression

Answer 279

The enzyme NO synthase converts arginine to NO which diffuses across membranes into other cells. NO binds to gauntly cyclase which produces cyclic GMP a second messenger. The result of increased cGMP is relaxation of smooth muscles which causes dilation of blood vessels.

Answer 280

They are very localized due to the instability of NO.

Answer 281

Angina is caused by inadequate blood flow to the heart. Nitroglycerin is converted to NO which causes dilation of blood vessels by creating cGMP. This lowers the blood pressure so if taken with other drugs that work in the same pathway, blood pressure could be lowered to dangerous or even fatal levels.

Answer 282

Cyclic AMP is a second messenger molecule common to signal transduction pathways. It is produced by adenylyl cyclase from ATP and degraded by phosphodiesterase to AMP.

Answer 283

It activates protein kinase A which phosphorylates enzymes in the cytosol or can travel into the nucleus and activate other proteins which regulate gene expression

Answer 284

Creates a toxin which irreversibly modifies the alpha subunit of Gs proteins by adding ADP-ribose. This prevents hydrolysis of GTP to GDP so the pathway is always active. This results in high cAMP levels causing a massive flow of water into the intestine and severe, life threatening diarrhea.

Answer 285

It is synthesized by guanylyl cyclase and degraded by cGMP phosphodiesterase

Answer 286

Phosphotidyl inositol in the plasma membrane can be phosphorylated in a variety of ways by PI kinases. One of these forms is PIP2. It can be broken down by phospholipase C to produce DAG and IP3. DAG remains in the membrane and binds to protein kinase C. IP3 triggers the opening of calcium ion channels in the ER causing the cytosol to be flooded with calcium. Calcium also binds to Protein kinase C and along with DAG activates it so that it will go on to phosphorylation other proteins

Answer 287

It is a monomeric G-protein that is activated downstream of almost all RTK’s. It activates the Map-kinase cascade which results in protein activity and gene expression related to survival. For this reason it is often mutated in cancers and is an important oncogene.

Answer 288

It is stimulated by Ras and other G-proteins. As a result of stimulation, Phosphatidyl inositol is phosphorylated at the 3 position hence PI3. This stays in the membrane but becomes active and activates other membrane proteins mostly related to growth and survival

Answer 289

It is a short pathway involved in inflammation and immunity

Answer 290

A short pathway involved in development. It uses serine/threonine kinases THF beta binds to its receptor which dimerizes and cross phosphorylates. Then it activates SMADs which travel to the nucleus to affect gene expression

Answer 291

1 Downregulation: Decrease in receptor synthesis or increase in degradation (occurs slowly) 2 sequestration: receptors internalized by endocytosis (occurs rapidly) 3 Inactivation of GPCR’s: GPCR’s are phosphorylated preventing interaction with G-proteins (occurs rapidly) This would occur in response to constant activation because of prolonged high concentration of substrate

Answer 292

G-protein-coupled receptor kinases (GRK’s) phosphorylated them and once phosphorylated they bind to arrestin molecule rather than G-protein

Answer 293

They are activated in response to epinephrine and norepinephrine. They are GPCR’s that activate a Gs protein which activates adenylyl cyclase pathway and protein kinase A. The end result is increasing contractility and heart rate.

Answer 294

Damage to the heart -> sympathetic response-> prolonged response -> desensitization of beta-adrenergic receptors-> decreased contractility and heart rate -> further weakens the heart Beta blockers can be used to treat heart failure because paradoxically they actually correct the beta adrenergic receptor number and GRK activity

Answer 295

2 transmembrane tyrosine kinase domains bound to two completely extracellular domains by disulfide bonds. The extracellular domains are bound together by disulfide bonds as well and together they form an active site for insulin binding

Answer 296

MAPK and PI3K-AKT pathways to induce glucose uptake, cell survival and proliferation Major effects on glucose regulation come through the PI3K-AKT pathway

Answer 297

Calcium ions are at a lower concentration in the cytoplasm than in the extracellular environment and in the ER because of ion pumps. Calcium ion channels can be opened in either location as a result of signaling which floods the cytoplasm with ions and can activate or deactivate other proteins

Answer 298

CFTR cystic fibrosis transmembrane conductance receptor It is located on exon 7 Functions as a Cl- ion channel in the ABC transporter family

Answer 299

Salty sweat Severe cough with thick mucus Digestive problems including leading to malnutrition Obstruction and infection of airways Damage to respiratory system and pulmonary disease (90% of mortality)

Answer 300

It has two membrane spanning domains with 6 transmembrane domains each. Each also bound to a nucleotide binding domain and one is attached to the cytoskeleton. The two subunits are attached by the R (regulatory) domain in between them. The R domain is unique and not similar to other ABC transporters.

Answer 301

Gating refers to the regulation that takes place to determine when it is open or closed. 1 cAMP activates PKA 2 PKA phosphorylates R domain 3 ATP is hydrolyzed in NBD1 to open channel 4 PKA phosphorylates more sites on R domain 5 NBD2 binds ATP which further opens channel 6 ATP hydrolysis at NBD2 results in release of ADP and channel closing 7 R domain dephosphorylation closes channel

Answer 302

I lack of CFTR II defective, misfolded CFTR (does not reach membrane) III defective gating IV Restricted Cl- movement thru channel V reduced protein (alternative splicing) VI accelerated turnover >85% are type II I-III are the most severe leading to pancreas insufficient phenotype V-VI are the most mild and lead to pancreas sufficient phenotype

Answer 303

Sweat ducts are divided into secretory coil and reabsorptive duct. Secretory coil does not contain CFTR and simply passes isotonic solution into the duct. This solution then passes through the reabsorptive duct where CFTR is found which normally causes uptake of chlorine leading to uptake of sodium but not water (because there are no aquaporins) this results in a hypotonic sweat solution. However, defected CFTR in CF patients limits reabsorption of salts leading to salty sweat

Answer 304

CFTR is located in bronchial ciliated cells. Goblet cells throughout the lungs secrete mucus into this area. Normally CFTR transports chlorine out of cell into the mucus where sodium remains and water is pulled out by osmosis to thin out the mucus. In CF patients, chlorine is not transported out and as a result sodium is reabsorbed into cells. These combine to cause water to move out of mucus into cells instead of the reverse and the resulting mucus is very thick. This thick mucus builds up obstructing airways and leading to inflammation and infection and ultimately scarring and lung disease.

Answer 305

Similar to the lungs, CF patients do not secrete chlorine leading to absorption of sodium and retention of water leading to viscous pancreatic juice. In addition, chlorine gradients created in part by CFTR are used for counter transport of bicarbonate out of the cells. In CF patients the chlorine gradient is not created and bicarbonate cannot be secreted. This leads to thick mucus blocking the release of enzymes into digestive tract and much of the food is not digested or absorbed which can lead to malnutrition. In addition, pancreatic beta cells can be damaged by mucus limiting insulin production and resulting in diabetes.

Answer 306

>10% function

Answer 307

Deletion of phenylalanine at position 508 of the gene. In the NBD1. Causes misfolding of protein which prevents it from reaching the plasma membrane

Answer 308

1 Gene therapy attempting to deliver functioning CFTR gene 2 Pharmacotherapy focused on trafficking protein with F508del mutation to the membrane that will be at least partially functional and may reduce or eliminate symptoms

Answer 309

It is possible that it confers a heterozygous advantage against cholera. Heterozygotes don’t show symptoms of CF but show less fluid loss and dehydration than the homozygous dominant phenotype. Cholera toxin enters intestinal cells and perpetually activates cAMP which activates CFTR in addition to other ion channels causing massive secretions of ions and water into the lumen leading to severe often fatal diarrhea. CF heterozygotes potentially are less harmed by cholera.

Answer 310

1 Ubiquitin proteasome- degrades short lived and damaged or misfolded proteins, it is selective 2 Lysosomal pathways- degrade long lived proteins and organelles, can be selective or random and is unregulated in response to cellular stresses.

Answer 311

Ubiquitin ligases E1 E2 and E3 With the use of ATP, ubiquitin is added to E1, it is then transferred to E2 and finally to the target protein with the help of the E3 enzyme.

Answer 312

There are hundreds of different E3 Ubiquitin ligase which each only add ubiquitin to a specific target protein

Answer 313

They are large protein structures made up of a central core which contains protease and ends which bind to target proteins and feed them thru the core where they are degraded by proteases and Ubiquitin is removed by ubiquitinases to be recycled in the cytoplasm.

Answer 314

It is the pathway by which cellular proteins and organelles reach the lysosome for degradation.

Answer 315

1 Macroautophagy- selective or random, large particles are engulfed in a double membrane which fuses with the lysosome 2 Microautophagy- selective or random- small particles and organelles invaginate directly into the lysosome to form a vesicle which is degraded along with its contents 3 Chaperone mediated autophagy- highly selective, Proteins with a specific amino acid motif are shuttled to the lysosome and transported through the membrane for degradation

Answer 316

Bits of membrane called isolation membrane or phagophore that are believed to be from the golgi or SER begin surrounding the target until they completely engulf it enclosing it within a double membrane. This is called an autophagosome. The outer membrane then fuses with the lysosome and the inner membrane is degraded along with the target.

Answer 317

Cancer, neurodegenerative diseases and many others

Answer 318

The lysosome begins to invaginate to engulf a target creating an autophagic tube which is more narrow especially at the ends. Eventually this buds off inside the lysosome to create a vesicle which is degraded along with its contents

Answer 319

Proteins with KFERQ motif bind to chaperone called hsc70 or hsc73 and are targeted to the lysosome. At the lysosome membrane they bind to LAMP2 which changes shape to become a transporter and allow them through to the inside of the lysosome where they are degraded.

Answer 320

``` 1 Nutrient deficiency 2 Growth factor withdrawal 3 Infection 4 Hypoxia 5 DNA damage ``` Genes responsible are called autophagy related genes or ATGs

Answer 321

It is a master regulator It activates genes related to growth/proliferation and inhibits autophagy related genes ATG limiting autophagy. Under cell stress, mTOR is inhibited allowing expression of ATGs and ultimately increased autophagy. Disregulation of mTOR can lead to obesity diabetes and cancer

Answer 322

Pharmacodynamics: What a drug does to the body Pharmacokinetics: What the body does to a drug

Answer 323

1 Receptors 2 Enzymes 3 Structural proteins 4 Transport proteins

Answer 324

Both bind with high affinity to the target. However agonists cause an effect upon binding and antagonists don't cause an effect. Usually this results in agonists activating a process and antagonists inhibiting a process

Answer 325

Orthosteric binding occurs at the active site and allosteric binding occurs away from the active site

Answer 326

Receptor vs non receptor (W/in non receptor) Chemical vs physiological (W/in Receptor) Orthosteric vs allosteric Both orthosteric and allosteric branch to be either reversible or non reversible. Orthosteric reversible is competetive

Answer 327

Competitive antagonists bind reversibly to the active site of the receptor while non-competitive bind away from the active site. Competitive antagonists reduce potency and can be overcome by increasing agonist concentration. non-competitive antagonists decrease efficacy and cannot be overcome by increasing concentration of agonist.

Answer 328

Physiological antagonists activate an opposite pathway | Chemical antagonists use some chemical interaction without the involvement of a receptor

Answer 329

``` Efficacy = how effective a drug is at a certain concentration. An effective drug has a high Emax or a high maximum effectiveness at high concentration Potency = at what concentration a drug becomes effective a potent drug has a low ED50 meaning it reaches half of its maximum effectiveness at a very low concentration. A dose-response curve is a graph of effictiveness vs concentration of a drug ```

Answer 330

A graph of % of people exhibiting an effect (therapeutic, toxic or lethal) vs concentration of drug. ED50 is the concentration at which 50% of people saw therapeutic effects. TD50 and LD50 are the same but for toxic and lethal effects respectively

Answer 331

TI = TD50/ED50. Therapeutic window is the dosage at which a drug will be effective for most people without being toxic to anybody. A narrow window is illustrated by a low TI and a wide window is illustrated by a high TI.

Answer 332

MS= LD1/ED99

Answer 333

Selectivity refers to whether the drug binds only to one receptor and not to any others. Selective drug action includes binding to only 1 receptor but also includes that receptor controlling only one process. High selectivity produces fewer side effects and highly selective drugs are usually safer although selectivity does not guarantee safety

Answer 334

ADME 1 Absorption- how much of it actually makes it to the blood stream 2 Distribution- Where in the body does it go 3 Metabolism - Breakdown of drug 4 Excretion- removal of drug in urine

Answer 335

1 Passive diffusion- most common 2 Facilitated diffusion 3 Active transport 4 Endocytosis

Answer 336

Different pH's could cause drugs that are weak acids or bases to change between protonated and non protonated states which results in differences in net charge between states. The uncharged state will always be absorbed better than the charged state. So weak bases should be in weak basic drugs to promote deprotonation and weak acids should be in weak acidic drugs to encourage protonation

Answer 337

What portion of the drug actually reaches systemic circulation. This is affected by absorption and metabolism in the liver

Answer 338

Amount of drug/concentration in the plasma This gives you the apparent volume in which the drug is distributed

Answer 339

Alpha- initial rapid decrease in plasma concentration due to distribution into the tissues and away from the central compartment Beta- gradual decrease in plasma concentration due to metabolism and excretion

Answer 340

Phase I = oxidation, hydrolysis, hydroxylation, deamination, and dealkylation Phase II = addition of large substituent groups to increase hydrophilicity

Answer 341

A class of enzyme that participates in phase I of drug metabolism under the following reaction NADPH + D + O2 + H+ -> NADP+ + H2O + DO Where d is the drug

Answer 342

First order: V = Vmax [C]/KM V is proportional to drug concentration Zero order: V = Vmax Velocity is constant at the maximum because of saturation

Answer 343

If the concentration is much higher than Km it will act as zero order If it is much lower than Km it will act as first order.

Answer 344

The amount of time it takes to remove half of the concentration of a drug from the plasma. First order: t1/2 = 0.693/k It is inversely proportional to the rate constant Zero order: there is no fixed half life because the rate of elimination is independent of concentration

Answer 345

Clearance is the volume of plasma cleared of a drug per unit time. Rate of elimination = CL * [drug] Half life = 0.693Vd/CL

Answer 346

When a drug is taken continuously or repeatedly before it is cleared from the system, it will build up. As the drug reaches higher concentrations, the rate of elimination increases until it equals the rate accumulation at the steady state. At this point, the concentration does not change as long as the drug is administered at the same rate. The steady state is reached after about 5 halflives. The time it takes to reach the steady state is the same no matter the rate of administration but that means that the concentration at the steady state is higher under more rapid administration

Answer 347

``` 1 Health 2AGE 3 Weight 4 interference by other drugs 5 Genetic variations ```

Answer 348

1 Avoid adverse drug reactions- genetic testing before prescription of drugs for those that are known to have adverse effects in individuals with certain genotypes. Example warfarin can cause severe bleeding in patients with CYP2C9 mutations 2 Improve efficacy of treatments- testing can be done before to determine how effective a drug could be based on genotype.- Example Trastuzumab is much more effective in patients with HER2-positive breast cancer 3 Improve cost-effectiveness of treatments- the previous 2 will necesarily cause this

Answer 349

Above 10% = no functions 4.5-10% = absence of vas deferens 1-4.5 = airway and sweat symptoms <1% = pancreas

Answer 350

The sweat chloride test

Answer 351

All babies receive an immunoreactive trypsinogen test (IRT) those with highest IRT receive a genetic panel including 23 of the most common mutations, if at least one mutation is present, a diagnostic sweat chloride test is undertaken

Answer 352

Meconium ileus (neonate) Failure to thrive (at any age) Chronic respiratory or sinus disease especially with sinus polyps Rectal prolapse

Answer 353

P. Aeruginosa | S. Aureus

Answer 354

``` Airway clearance Vest Albuterol Hypertonic saline Pulmozyme Bacterial suppression Inhaled antibiotics Digestion aids Pancreatic enzymes Vitamin supplementation Lung transplant Ivacaftor- potentiator which increases the function of CFTR at the membrane (only treats 4% of mutations) Combined therapies of potentiators and correctors Lumacaftor-ivacaftor Tezacaftor-ivacaftor ```

Answer 355

``` Compounds allowing read through of stop codons would prevent truncation and possibly produce an at least partially functional protein in mutations resulting in premature stop codons Class I Correctors would allow proteins which do not reach the membrane because of misfolding to at least reach the membrane where they could show at least some function - class II Potentiators- improve the function of proteins which are already at the membrane- classes iii-vi All three combined could treat most mutations and could show greater improvements to class i and II mutations than any one alone ```

Answer 356

The poly T tract is a string of repeated thymine in the intron between exons 8 and 9 in CFTR gene. Individuals have varying numbers of T’s. 9 and 7 T’s are normal while 5T’s cause exon 9 to not be included in the transcript many times resulting in fewer functional copies of CFTR protein. Individuals homozygous for 5T usually have about 10% CFTR function and therefore usually do not show symptoms. The TG tract is another locus adjacent to the poly T tract which also has a variable number of repeats. Normal is 9-11 TG’s. If an individual has 12 or 13 TG’s on the same gene where they are 5T, exon 9 is included less often leading to a more severe phenotype. It can be difficult to tell by genetic testing if these two traits are cis (on the same gene) or trans on opposite copies) so genetic testing of one parent of an individual may be necessary. Compound heterozygotes for 5T and other disease causing CFTR mutations could have varying disease symptoms Of note is that combination of 5T allele with the Arg117His mutation can lead to disease phenotype although neither mutation alone does

Answer 357

Targeted testing- only focuses on a few mutations so should only be used in those individuals whose families have a history of specific mutations Panels- tests for 23 mutant alleles- cheapest and easiest option for most people but may not catch more rare mutations Sequence analysis + duplication deletion testing- very expensive and slow, will catch almost everything but may catch unknown mutations or mutations with unknown phenotypic effects

Answer 358

2 ATP (net) 2NADH pyruvate will be turned into acetyl coa and enter the TCA cycle. Anaerobic: Only those 2 ATP per glucose Aerobic 30-36

Answer 359

``` glucose 1-> glucose 6P 2-> fructose 6P 3-> fructose 1,6BP 4-> GAP 5-> 1,3BPG 6-> GAP3P 7-> Gap2P 8-> PEP 9-> Pyruvate ATP used: 1, 3 ATP produced: 6, 9 NADH produced: 5 Preparative phase 1-4 ATP generating phase: 5-9 ```

Answer 360

1 Conversion of amine nitrogen to urea to be excreted 2 Conversion of carbon skeleton into one of 7 metabolites depending on whether amino acid is ketogenic glucogenic or both

Answer 361

In response to hormonal signals, lipases create fatty acids from triacyl glycerols in fat cells. These are transported through the blood attached to albumin until they reach the cell and transported across the membrane by fatty acid binding proteins. In the cytosol, fatty acyl coa synthetase attaches COA to the carboxylic acid portion. Carnitine palmitoyl transferase 1 CPT1 then replaces coa with carnitine and a translocase protein moves the carnitine fatty acid into the mitochondrial matrix where CPT 2 converts it back to a fatty acyl COA. Deficiency of CPT 2 is the most common disorder affecting this process

Answer 362

1 Creation of trans double bond between alpha and beta carbons with the reduction of FAD to FADH2 2 Addition of water at the beta carbon 3 Oxidation of the beta carbon to a ketone with the reduction of NAD+ to NADH 4 Attack by COASH to produce acetyl coa and a shorter fatty acyl coa

Answer 363

Different enzymes exist for beta oxidation of short, medium and long chain fatty acids. Medium chain acyl coa dehydrogenase MCAD deficiency is the most commonly deficient

Answer 364

Odd number: it is the same until the last round where the products are 1 acetyl coa and 1 propionyl coa (3 carbons) propionyl coa is converted to succinyl coa which enters the TCA cycle Unsaturated: Enoyl coa isomerase shifts double bond into correct position. If needed before enoyl coa isomerase functions, dienoyl coa reductase will remove a double bond by reducing it with FADH2

Answer 365

Oxidation begins in the peroxisome instead of the mitochondrial matrix. For VLCFA's they are oxidized into smaller pieces which are sent to the mitochondria for further oxidation. Branched fatty acids can undergo alpha oxidation which removes one carbon as co2 to line up branches in the alpha position and then undergo beta oxidation where half of the products are propionyl coa.

Answer 366

A form of fatty acid metabolism that occurs in the ER of kidney and liver cells in which the omega end of the fatty acid is first oxidized three times to form a carboxyllic acid and then beta oxidation occurs until you are left with a small molecule with carboxylic acid groups on either end. This molecule can be succinate which enters TCA cycle or adipate which is excreted. This occurs primarily under conditions where beta oxidation is limited.

Answer 367

1 Hormonal stimulation leads to breakdown of triacylglycerols increasing beta oxidation 2 Malonyl coA, a substrate in fatty acid metabolism inhibits CPT1 which prevents fatty acids from entering the mitochondria and therefore inhibits beta oxidation It is high under fasting, exercise conditions and after eating a meal high in fat

Answer 368

The production of ketone bodies from acetyl coA in the liver. 2 of the three ketone bodies travel elsewhere in the body where they are converted back to acetyl coA for TCA cycle. This process is overseen by HMG-coA synthase

Answer 369

TCA stands for Tricarboxylic acid cycle, it is the process that occurs with acetyl coa produced in metabolism of lipids carbohydrates and proteins and its purpose is to create NADH and FADH2 to power oxidative phosphorylation. Inputs: Acetyl Coa, oxaloacetate Outputs: 3NADH 1 FADH2 1 GTP 2CO2

Answer 370

``` 1 Oxaloacetate + acetyl coa to citrate Enzyme: citrate synthase 2 Citrate to isocitrate Enzyme: Aconitase 3 Isocitrate to alpha ketoglutarate Enzyme: isocitrate dehydrogenase +NADH +CO2 4 Alpha ketoglutarate to succinyl coA Enzyme: alpha ketoglutarate dehydrogenase +NADH +CO2 5 Succinyl coA to Succinate Enzyme: Succinate synthetase +GTP 6 Succinate to fumarate Enzyme: Succinate dehydrogenase +FADH2 7 Fumarate to malate Enzyme: Fumarase 8 Malate to oxaloacetate Enzyme: Malate dehydrogenase +NADH ```

Answer 371

The process by which oxidation of NADH and FADH2 with oxygen as the electron acceptor is paired to the phosphorylation of ADP. It is the major source of cellular ATP

Answer 372

Nucleotide diphosphate kinase

Answer 373

NADH: 3 FADH2: 2

Answer 374

NADH-> Complex I (transmembrane and pumps 4 H+)-> Coenzyme Q (lipid soluble within the membrane and moves to next complex) -> Complex III (transmembrane and pumps 4 H+ -> cytochrome C (water soluble on the outside of the membrane moves to next complex) -> Complex IV (transmembrane and pumps 2 H+) -> O2 (becomes H20)

Answer 375

F0F1-ATP synthase It uses the electrochemical gradient of protons formed by the electron transport chain for energy. As protons pass through the enzyme which is transmembrane, they cause the C subunit to rotate which results in structural changes to the alpha and beta subunits resulting in phosphorylation of ADP

Answer 376

It is used for ion transport across the inner membrane and is released as heat

Answer 377

Heart cell: results in decreased rate and force of contraction Salivary cell: secretion Skeletal muscle: contraction

Answer 378

Arginine, NO synthase (NOS)

Answer 379

They are signaling proteins involved in the immune system and inflammation, they generally bind to JAK -STAT receptors

Answer 380

beta adrenergic: GPCR’s JAK-STAT- enzyme associated ie they are not built in Insulin- Receptor with a built in tyrosine kinase (RTK) TGF beta - Receptor with a built in serine threonine kinase

Answer 381

Adenylyl cyclase-> cAMP -> PKA-> gene expression and protein changes in cytosol guanylyl cyclase-> CGMP-> smooth muscle relaxation and vasodilation PI kinases-> PIP-> DAG + IP3 -> PKC

Answer 382

Ras-> Map kinase -> protein activity and gene expression -> cell survival PI kinases -> PI3 -> protein activation -> cell survival and growth

Answer 383

Transport from one side of the cell to another by vesicles. This is one of the possible fates of receptors taken up into the early endosome by receptor mediated endocytosis

Answer 384

They are vessicle coating proteins involved in transport from the ER to the golgi

Answer 385

Pancreatic acinar cells produce and excrete exocrine digestive enzymes. This thick juice and lack of bicarbonate blocks pancreatic ducts and prevents exocrine secretions. Eventually this causes the acinar cells to die leading to pancreatic fibrosis and pancreatitis

Answer 386

It is a major sodium ion transporter Channel in cellular membranes. Normally, the CFTR protein inhibits eNAc reducing sodium reabsorption but in cystic fibrosis, it is active because CFTR cannot inhibit it so sodium flows into the cells making symptoms worse.

Answer 387

Gly551Asp | Class III - protein reaches plasma membrane but has gating issues

Answer 388

1 Hypochloremia - (Alkalosis) 2 Hyponatremia - (dehydration, failure to thrive) 3 Hypoproteinemia 4 Vitamin E deficiency (Hemolytic anemia) 5 Vitamin K deficiency- (bleeding diathesis) 6 Zinc deficiency- (acrodermatitis)

Answer 389

> 60 mmol/liter = diagnosis 30-59 = Grey zone possible CF <30 = NOrmal

Answer 390

1 CYP2D6 2 CYP2C19 3 CYP2C9 4 CYP2A6

Answer 391

Poor intermediate efficient and ultra rapid metabolizers. This determines how much drug or prodrug they will need. For example a poor metabolized would need very low dose of drugs and very high dose of prodrug

Answer 392

Anti psychotic drugs Tricyclic antidepressants Metoprolol (antihypertensive) Tamoxifen (anti-estrogen)

Answer 393

CYP2C9 and VKORC1

Answer 394

1 Glycerol 3-phosphate shuttle | 2 Malate aspartate shuttle

Answer 395

``` 1 palmitate (c16) 2 stearate (C18) 3 oleate (C18:1) 4 inoleate (C18:2) ```

Answer 396

Animal fat: saturated and monounsaturated long chain fatty acids Dairy fat: medium chain fatty acids (C6-C12) Vegetable oils: linoleate and other polyunsaturated fatty acids

Answer 397

It produces precursors to important processes: Gluconeogenesis Heme synthesis Amino acid synthesis

Answer 398

Buildup of Lactic acid because it is the breakdown product of pyruvate when the citric acid cycle is being underutilized. This is a common symptom of metabolic disorders. It occurs under anaerobic conditions such as strenuous exercise, or under disease conditions preventing full functioning of TCA cycle and/or oxidative phosphorylation

Answer 399

Pyruvate kinase catalyzes the final step of glycolysis from PEP to pyruvate (with the production of 1 ATP) Symtoms: Chronic hemolytic anemia- reduction of ATP limits sodium-potassium pump in RBC’s leading to ion imbalance Increased 2,3BPG levels- converted from 1,3BPG which builds up. Inhibits hexokinase resulting in further reductions in ATP productions. Also alters hemoglobin to allow more oxygen to be released in tissues which counteracts some of the symptoms Treatment: Blood transfusions, splenectomy, iron chelation, bone marrow transplant

Answer 400

Pyruvate dehydrogenase catalyzes the conversion of pyruvate to acetyl coA to enter the citric acid cycle and generates 1 NADH in the process. X-linked recessive because most mutations affect E1alpha subunit Symptoms: Metabolic form- severe presents with overwhelming lactic acidosis Chronic neurological form- moderate lactic acidosis and severe brain dysfunction and abnormalities. (Most common in females) Treatment: high fat/low carb diet, thiamine supplement, sodium bicarbonate and citrate for acidosis, dicholoroacetate (inhibits E1 regulatory kinase which lowers protein function)

Answer 401

Converts pyruvate to oxaloacetate for entrance into TCA cycle and other pathways Cofactor = biotin

Answer 402

Symptoms: Lactic acidosis, hypoglycemia (decreased gluconeogenesis), failure to thrive, decrease in myelin sheaths leading to developmental delay, recurrent seizures and neurological dysfunction Treatment: NO EFFECTIVE TREATMENT Can attempt: hydration, glucose, citrate, biotin, aspartate, avoidance of fasting, high carb/protein diet (to prevent gluconeogenesis which uses up oxaloacetate)

Answer 403

Cyanide binds to Fe3+ in cytochrome oxidase in complex 1 of the electron transport chain. Prevents oxidative phosphorylation and causes switch to anaerobic metabolism leading to massive acidosis and hyperventilation and rapid death. Treatment: Nitrite (oxidizes hemoglobin to Fe3+ state to bind cyanide and remove it from cytochrome oxidase)

Answer 404

Rhodanase in the liver converts it to thiocyanate which is harmless

Answer 405

1 Maternal inheritance 2 heteroplasmy (replicative segregation) 3 high mutation rate -> late onset 4 affects tissues with high energy demand- vision, hearing, smell and neurons generally affected

Answer 406

``` 1 MELAS 2 LHON 3 Kearns-sayer syndrome 4 NARP 5 MERRF 6 Pearson syndrome 7 Leigh disease ```

Answer 407

Late onset Ptosis (drooping of eyelids due to inability to open them) Ophthalmoplegia paralysis of muscles in and around the eye

Answer 408

Myoclonic epilepsy and ragged-Red Fiber disease Late onset in late childhood or in adulthood. Caused by a mutation to the mitochondrial gene which codes for lysine tRNA. Symptoms: myoclonic epilepsy (muscle twitching) short stature, poor night vision, hearing loss, lactic acidosis and exercise intolerance Treatment: none effective but can try coenzyme q and L-carnitine

Answer 409

Leber’s hereditary optic neuropathy Caused by 1 of 3 mutations to mitochondrial gene for NADH dehydrogenase subunits (complex 1 of ETC) Symptoms: acute, sudden onset of blindness in young adults caused by degeneration of retinal ganglion cells of optic nerve. Treatment: Idebenone (experimental)- boosts electron transport chain and allows bypass of complex 1

Answer 410

Inability to breakdown medium chain fatty acids (C6-C12) leads to acute energy deficiency, hypoketotic hypoglycemia and elevated levels of C8 acylcarnitine and DICARBOXYLIC ACIDS (results from omega oxidation) Commonly presents in healthy children 3-24 months as sudden hypoketotic hypoglycemia triggered by illness or prolonged fasting. Symptoms also include: vomiting, lethargy, liver failure, seizure, coma and death. If caught early, prognosis is very good but can be fatal if undetected Treatment: avoidance of fasting, glucose supplementation, low-fat diet, carnitine suplementation

Answer 411

1 Adult: mild myopathy form. Presents as rhabomyolysis (breakdown of muscle fibers leading to myoglobin the urine causing it to be rust colored) induced by exercising, fasting, high fat diet, cold temperature or infection 2 Infantile- severe hypoketotic hypoglycemia, liver failure, cardiomyopathy, and peripheral myopathy 3 Neonatal- lethal within 4 days. Respiratory failure, hypoglycemia, seizures, hepatomegaly, liver failure, cardiomegaly Treatments: Avoidance of fasting, extreme exercise and lipid intake High carb/low fat diet, high intake of medium chain fatty acid triheptanoin and others, carnitine supplement

Answer 412

Propionic academia- acts on first step from propionyl coA to D-methylmalonyl coA. Biotin is a cofactor Methylmalonic acidura - acts on the third step from L-methylmalonyl coA to succinyl coA. B12 is a cofactor Symptoms: poor feeding, lethargy, vomiting, acidosis, hypotonia, seizures, coma can be life threatening Treatment: Low protein diet, specialized amino acids, antibiotic against gut bacteria which produce propionyl coA CAUSED BY BUILDUP OF ORGANIC ACIDS WHICH ARE TOXIC

Answer 413

Caused by defect in alpha oxidation in the peroxisome leading to a build up of phytanic acid (branched fatty acid) which becomes toxic at high levels Clinical features: retinitis pigmentosa, anosmia, progresses to blindness, deafness, sensory neuropathy, cerebral ataxia, cardiomyopathy Treatment: dietary restrictions to avoid phytanic acid

Answer 414

1 Zellweger syndrome (ZS): severe 2 Neonatal adrenoleukodystrophy (NALD): intermediate 3 Infantile refsum disease (IRD): least severe Caused by a defect in peroxisome biogenesis leading to a build up of very long chain fatty acids and branched fatty acids (phytanic acid) and decreased levels of some lipids Symptoms: ZS- present as newborns or early childhood with hypotonia (decreased muscle tone) and distinct facial dysmorphism, seizures and liver dysfunction. No sight, hearing or psychomotor development and death within 1 year IRD- present with progressive loss of hearing, vision, smell and motor function

Answer 415

Caused by a defect in ABCD 1 gene that encodes transport of VLCFA’s into peroxisome leading to accumulation in plasma and tissues and damage to the myelin sheath and adrenal cortex resulting in progressive motor dysfunction and adrenal insufficiency heterozygous females show some symptoms later in life 1 Cerebral demyelination form: presents in childhood (4-10) as inflammatory demyelination with rapid progression to vegetative state 2 Adrenomyeloneuropathy (AMN): milder form. Presents in young adults as non-inflammatory distal axonopathy with gradual progression to a spastic paraplegia. No treatment

Answer 416

``` 1 calorie 2 Kilocalorie 3 Calorie 4 Joule 5 Kilojoule 1000 calories = 1 Kilocalorie = 1 Calorie = 4180 Joules = 4.18 Kilojoules ```

Answer 417

1 Direct calorimetry - measures the amount of energy that is released when the food is combusted completely 2 Indirect calorimetry - estimates the amount of energy in food in the body by measuring oxygen consumed, CO2 produced and Nitrogen excreted while metabolizing that food Indirect calorimetry is more commonly used and is usually slightly lower than direct calorimetry

Answer 418

``` Carbohydrates: 4 Kcals per gram Proteins: 4 Kcals per gram Fat: 9 Kcal per gram Alcohol 7 Kcal per gram The energy is a function of how reduced the nutrient is ```

Answer 419

The nutrients are nearly the same in calories per oxygen but vary more in calories per CO2 with Protein being the highest then fat and finally carbohydrates

Answer 420

The ratio CO2 produced/O2 used during metobolism of a given substance. This is used to determine how much energy is contributed by different foods in a mixed diet Carbohydrates = 1 Protein = 0.8 Fat = 0.7

Answer 421

10 minutes : muscle glycogen 10-20 : muscle and liver glycogen >20 minutes: muscle and liver glycogen and fatty acids > 2 hours : fatty acid At this point gluconeogenesis is used to maintain blood glucose levels but can only do so for a short period of time thus if exercise is continued longer, hypoglycemia may occur.

Answer 422

The number of calories per gram of a food

Answer 423

1 Basal metabolism (energy required to run cellular functions to stay alive) 50-70% 2 Physical activity: 15-30% 3 Thermic effect of food (energy required to process certain foods) 10%

Answer 424

Lean body mass. Muscle takes more energy to maintain than adipose tissue so the more muscle you have as a percentage of body weight, the higher the BMR

Answer 425

The amount of extra heat produced during ingestion of a food because of energy required to digest, absorb and distribute its nutrients (the energy lost from food) Carbohydrates: 10% Fat: 5% Protein: 20-30%

Answer 426

Macronutrients are needed in large quantities: carbohydrates, proteins and fats Micronutrients are needed in much smaller quantities: vitamins and minerals

Answer 427

0.8 g/kg body weight/day

Answer 428

Small intestine, by active transporters. More than one amino acid uses the same transporter so there can be competition for absorption

Answer 429

``` PVT TIM HALL 1Phenylalanine 2Valine 3Tryptophan 4Threonine 5Isoleucine 6Methionine 7Histidine 8Arginine 9Leucine 10Lysine ```

Answer 430

Amino acids that are not normally essential but become essential for an individual because of disorders that make them unable to produce that amino acid

Answer 431

Protein quality refers to the mix of essential amino acids that a protein contains and the amounts of each compared to the ideal Complete = Can maintain life and normal growth as the sole source of protein Partially complete = can maintain life but not growth Incomplete = cannot maintain life

Answer 432

Biological value- measures percentage of absorbed amino acids retained for protein synthesis BV = Dietary N - (UrinaryN-UrinaryN0)-(FecalN-FecalN0)/DietaryN-(FecalN-FecalN0) *100 Net protein utilization- percent of nitrogen intake that is retained in the body NPU = DietaryN-(UrinaryN-UrinaryN0)-(FecalN-FecalN0)/FoodN eaten *100 Protein efficiency ratio PER = weight gain in an animal/weight of protein ingested during that period of time Chemical score- compares amino acids of a protein to egg (a high quality protein) to determine limiting amino acid CS = mg essential amino acid per gram of test protein/mg essential amino acid per gram of egg protein *100 Protein digestibility corrected amino acid scoring- compares amino acids in a protein to the human requirement pattern of a 2-5 year old to determine limiting amino acid AAS = mg of EAA in 1g test protein/mg of EAA in 1g protein requirement pattern PDCAAS = lowest AAS ratio *true protein digestibility

Answer 433

Some amino acids can fulfill one of the demands of another amino acid reducing the amount of the second amino acid that is needed. For example, cysteine like methionine can provide sulfur so if there is a lot of cysteine present in a food, methionine is not needed in as high of quantities

Answer 434

Two poor quality proteins which differ in the limiting essential amino acid will form a higher quality protein when mixed together or ingested within about 24 hours of each other

Answer 435

Kwashiorkor- severe protein deficiency leading to edema and extended abdomen, mental apathy, changes in skin and hair pigmentation, Retarded growth and muscle wasting, rapid progression and high mortality. Often occurs when a second baby is born and the first is abruptly weaned from the mother’s milk and fed a diet of inadequate protein Marasmus- Protein calorie malnutrition. Condition develops gradually over several months or years and shows growth retardation and wasting away of fat and muscle tissues but with mental alertness and appetite present. Low mortality

Answer 436

1 >100 grams per day 2 50% of calorie intake 3 Rely mostly on complex carbohydrates

Answer 437

Ketosis, loss of cations, dehydration, excessive breakdown of body protein

Answer 438

Available are those which can be digested by the body and used for energy Unavailable cannot includes Insoluble and soluble

Answer 439

Dietary fiber is what remains after intestinal digestion- soluble, insoluble and non-carbohydrate Crude fiber is what remains after acid and alkaline digestion in a lab- Insoluble and non-carbohydrate only Added fiber is what is often isolated and added to foods for the benefits associated with fiber Soluble and insoluble

Answer 440

1 Reduce incidence of diseases such as diverticulitis, hemorrhoids, cardiovascular disease and hyperlipidemia 2 Promote weight loss by creating a feeling of fullness 3 Stimulate peristalsis and prevent constipation 4 Facilitate removal of cholesterol and other sterols in the feces 5 In diabetes, promote glycemic control and reduction of hyperlipidemia

Answer 441

Lists a number of groups and foods within those groups along with serving levels which all have approximately the same composition as other members of the group. This is meant to allow for easy exchanges without extensive calculations

Answer 442

A measure of how much a certain carbohydrate raises the blood glucose levels. High glycemic index foods are linked to diabetes and heart disease Glycemic load is the glycemic index multiplied by the grams of carbohydrate and divided by 100

Answer 443

Glycerides, phospholipids and sterols

Answer 444

Humans cannot produce omega 3 and omega6 double bonds so we require these in our diet (linoleum acid omega 6 and alpha linolenic acid omega 3) If not present in the diet the condition essential fatty acid deficiency occurs causing dermatitis, alopecia, thrombocytopenia, and growth retardation

Answer 445

Fats with a trans double bond. Naturally occurring fats are all cis double bonds but in some food processing trans bonds occur. They act more like saturated fatty acids and are known to elevate risk of cardiovascular disease 1 higher melting point 2 increasing LDL/HDL ratio 3 inhibit delta six desaturase: catalyzes production of arachidonic acid 4 Increases shelf life of foods 5 present in fried foods

Answer 446

A disorder that results from too little or too much of essential nutrients Primary occurs as a result of imbalanced or insufficient diet Secondary occurs from defective assimilation or utilization of nutrients Primary can be fixed by dietary changes alone but secondary may require medication and/or surgery

Answer 447

Amounts of various nutrients that provide adequate nutrition for 97.5% of people within a group of the same sex and age Note that it is meant mainly to avoid insufficient nutrition and is therefore set 2 standard deviations above what is necessary for the average person in that group

Answer 448

Newer guidelines than RDA which aim to avoid chronic diseases in addition to insufficient nutrition. Includes: Estimated average requirement (EAR): like RDA but for the average person in the group instead of 2 standard deviations above Adequate intake (AI)- amount that appears to sustain good health in a group of people. For foods with insufficient scientific evidence to be an RDA Tolerable upper intake level (UL)- the highest level of a nutrient that will pose no risk of adverse effects for 98% of people

Answer 449

Body fat percentage. Men: > 25% = obese Women: > 32% = obese

Answer 450

``` BMI = body weight (kg)/height in meters^2 or body weight (lbs) *703/height in inches^2 Underweight = <18 Healthy = 18-25 Overweight = 25-30 Stage 1 obesity = 30-35 Stage 2 = 35-40 Stage 3 = 40+ ```

Answer 451

Abdominal/visceral: located between organs and abdominal wall. More highly associated with increased risk of CVD, diabetes etc. Subcutaneous (peripheral) : just below the skin especially in the hips, thighs and buttocks. Poses less of a health risk

Answer 452

The waist is measured at the narrowest point and the hips measured at the widest point. WHR = waist circumference/hip circumference >1 means at higher risk for diseases It shows much higher correlation than BMI with risk for diseases because it takes into account location of fat deposits however it is more difficult and awkward for the patient to be measured

Answer 453

1 Increased sedentary lifestyle 2 Availability and marketing of cheap processed energy dense foods 3 genetics does not fit our lifestyle

Answer 454

Worldwide: developed countries have a higher risk US: poor and minorities at higher risk

Answer 455

During periods of weight gain adipocytes grow in size but also proliferate however during periods of weight gain, they only shrink but their numbers do not decrease. This can stifle weight loss because it is hard to reduce adipocytes size below a threshold. In juveniles weight gain contributes more to the number of adipocytes than in adults. Thus if a young person becomes obese they will have a larger number of adipocytes that will contribute to problems accumulating fat throughout their life

Answer 456

40-70% heritable Yes there are some monogenetic disorders leading to obesity but they are extremely rare and do not account for rising obesity

Answer 457

Many Pima Native Americans migrated from Mexico to Arizona after the Mexican American war leaving two distinct populations. In the early 1900’s American Pimas had similar incidence of diabetes as the US population however by 1950 prevalence was 10X higher than US population. When compared to Mexican Pimas, prevalence is much higher in the US population due to adoption of an American diet. This shows that this group is genetically predisposed to diabetes, so environmental factors such as poor diet have a huge effect on them

Answer 458

The theory that certain processes in our body maintain equilibrium at a set point and will resist if we try to deviate too far in either direction from that set point. This is applied to obesity to say that there is a certain set point weight for each person that their body gravitates towards and will resist changes from that weight. This is supported by evidence showing that people who lose weight often cannot keep it off and that after weight loss people report feeling more hungry in the time after the meal than they did before weight loss

Answer 459

``` 1 Leptin- produced in adipocytes and acts to decrease food intake. Leptin secretion is lowered after weight loss and highered (to a lesser degree after weight gain) supporting the set point theory 2 Ghrelin - peptide released in the stomach and acts to stimulate the hypothalamus to release hormones and increase food intake. Fasting and hypoglycemia bring it on 3 PYY- polypeptide produced in the ileum and colon that suppresses appetite and food intake and slows the passage of nutrients through the gut 4 Orexin (a and B)- peptides made in the lateral hypothalamus which stimulate appetite and cause increased food intake- they also promote wakefulness in the day and sleep at night ```

Answer 460

People who are sleep deprived have less leptin and more ghrelin and are therefore more likely to intake more food and gain weight

Answer 461

1 Adjustable gastric banding- a band is placed on the stomach to limit the amount of space available in the stomach 2 Gastric bypass- the opening of the stomach is attached to the small intestine so that food does not pass through the stomach or much of the small intestine leaving only a small pouch. This limits the amount of food that patients eat and also limits their ability to absorb nutrients 3 Sleeve gastrectomy- A portion of the stomach is removed so that the stomach pouch is much smaller. These are recommended only for patients with stage 3 obesity

Answer 462

1 Organic compound 2 Cannot be synthesized in sufficient quantities and therefore some must come from the diet 3 Are not metabolized to directly provide energy

Answer 463

Fat soluble D,E, A, K Water Soluble C, B complex

Answer 464

Fat soluble by passive diffusion Water soluble by facilitated transport Fat soluble vitamins unlike water soluble vitamins cannot become saturated and therefore it is more likely to have an over abundance of fat soluble vitamins than of water soluble vitamins

Answer 465

Active form = calcitriol It is similar to cholesterol with 4 hydrophobic rings We can obtain it in our diet from animals but not plants or we can make it from cholesterol but this requires UV light which can be problematic in some places It functions to alter gene expression in order to increase intestinal absorption of calcium ions in response to parathyroid hormone In a deficiency, parathyroid hormone relies instead on uptake of bone calcium to raise plasma concentration leading to defective mineralization of the bone called rickets in children presenting with bowed legs, retardation of growth and plump appearance or osteomalacia in adults

Answer 466

Yes in very high doses it can become toxic. It is extremely rare and seen mostly in response to abuse of supplements. Causes anorexia, excessive thirst, vomiting, weight loss, hypercalcemia, calcium deposits in soft tissue and if chronic enough can lead to atherosclerosis and cardiac myopathy

Answer 467

Retinal, retinol, and retinoic acid It is a single 6 membered ring with a long branched unsaturated carbon containing one polar group It is rich in both animal and plant foods

Answer 468

1 Retinal is important in vision. It is bound to opsin to create rhodopsin and the retinal portion undergoes a change from cis to trans double bond when hit with UV light which is important for vision 2 Modifies gene expression to enhance differentiation and proliferation especially in epithelial and immune cells and in development A deficiency could occur as a result of malabsorption disorders or a diet that is too heavily based on one thing such as white rice with little vitamin A. It presents as night blindness, hyperkeratosis of epithelial cells where immature skins cells accumulate are dry with a high production of keratin, also xerothalmia or hyperkeratosis of the cornea can occur which ultimately can lead to infection and blindness

Answer 469

We get about half of our vitamin K from animal and plants in our diets and the other half from intestinal bacteria It allows the post-translational modification of adding CO2 to glutamate which is important for several clotting factor proteins. Deficiency leads to severe bleeding Deficiencies are rare and occur in adults in response to malasorptive syndromes or prolonged use of certain antibiotics or warfarin. It is assumed in infants b/c they don’t have gut bacteria and vitamin K and limited amounts in placenta and breast milk so all infants are given supplements

Answer 470

Function is not well understood. It is thought to have non specific antioxidant effects Deficiency can occur from a mutation called AVED which results in retinopathy and neuropathy related to oxidative damage of the photoreceptors and neurons respectively. Can also result from malabsorptive syndromes

Answer 471

Vit. Source. Deficiency. Toxicity Endow Plant. Animal. Gut. Risk. Disorder A. Y. Y. Diet Visión, hyperkeratosis Y D. Y. Y. Sunlight, diet Rickets, osteomalecia. Y E. Y. Y. Genetics. AVED K. Y. Y. Y. Birth. Bleeding and bruising

Answer 472

Thiamine Active form = TPP Cofactor for decarboxylation reactions such as pyruvate dehydrogenase and alpha ketoglutarate and amino acids Used in citric acid cycle, pyruvate dehydrogenase, amino acid catabolism and pentose phosphate pathwat

Answer 473

Limited commodities diet such as only eating white rice or alcoholism Symptoms include Wernicke-Korsakoff syndrome of neurological impairments and the more severe beriberi leading to anorexia, muscle weakness, peripheral paralysis and edema

Answer 474

Riboflavin Active forms FMN and FAD Cofactors which catabolize oxidation reduction reactions in metabolism. Involved in electron transport chain, TCA cycle, beta oxidation

Answer 475

Pathology of skin and mucous membranes | Glossitis- tongue, Cheilosis- lips, sebhorreic dermatitis-scalp face and torso

Answer 476

Niacin active form nicotinamide NAD and NADP | Cofactor for oxidation reduction reactions in many pathways of metabolism

Answer 477

Diet consisting of a limited commodity: corn Hartnup disease- mutation affecting absorption of niacin precursor Isoniazid antibiotic over long times Signs / symtoms: pellagra- dermatitis,diarrhea and dementia

Answer 478

Pantothenate active form coenzyme A | Cofactor and acyl group carrier for a variety of metabolic processes

Answer 479

Pyridoxine active form = pyridoxal 5-phosphate | Coenzyme for transamination reactions in amino acid metabolism thus it is required for synthesis of all amino acids

Answer 480

Risks: Isoniazid antibiotic Signs/symptoms Macricytic anemia (large immature RBC’s), pathology of skin and mucous membranes

Answer 481

It can be de phosphorylated which makes it less hydrophilic and allows some passive diffusion uptake. Toxicity occurs as a result of abuse of supplements Symptoms Nerve damage to arms and legs and sensitivity to sun all are reversible if supplement is stopped

Answer 482

Biotin active form: biotin | Cofactor for carboxylases in many processes of metabolism

Answer 483

Risks Genetic, long term antibiotic use, over reliance on raw eggs in diet Signs/symptoms: Neurologic and dermatitis

Answer 484

Folic acid Active form THF Important in one carbon metabolism such as synthesis of amino acids, purines and thymidine Necessary for any rapidly dividing tissues

Answer 485

``` Risks Pregnancy Over reliance on goat’s milk Symptoms: Macrocytic anemia Fatigue Tongue lesions Birth defects including spinal bífida ```

Answer 486

Cobalamin | Required to synthesize active folate

Answer 487

It is ingested bound to proteins -> haptocorrin in the stomach -> Intrinsic factor in the intestine-> translocator in intestine -> transcobalamin i, II or iii in blood It is much larger than other water soluble vitamins

Answer 488

``` Risks Strict vegan diet Loss of intrinsic factor Symptoms Megaloblastic macrocytic anemia Pins and needles and numbness in hands and feet, psychiatric disorders ```

Answer 489

Ascorbic acid It is an important water soluble antioxidant especially functioning in neutrophils against infection it is also an electron donor for hydroxylations such as the formation of collagen

Answer 490

Risks Diet Symptoms Scurvy - Rupture of small blood vessels, weakening of bones and swelling of joints

Answer 491

Keshan disease- cardiomyopathy in selenium deficient children triggered by stress, viral infection or chemical exposure

Answer 492

Vit. Source. Deficiency. Toxicity Endo Plant Animal Gut. Risk. Disorder B1 Y. Y. alcoholism Beriberi and Wernicke-Korsakoff B2. Y. Y. Light B3. Y. Y. Y. Hartnup, low B6. Pellagra. y B5 Y. Y B6 Y. Y. Isoniazid macrocytic anemia. Y-passive uptake B7 Y. Y. Y. Antibiotics B9. Y. Y. Pregnancy. Macrocytic anemia/birth defects B12. Y. Diet, loss of IF macrocytic anemia, nerve damage C. Y. Diet. Scurvy

Answer 493

Weight loss or improper growth Extreme fear of weight gain Weighs less than 85% of expected weight

Answer 494

Repeated binge consumption followed by compensating behaviors which include: vomiting, fasting, laxatives, and excessive exercising

Answer 495

Repeated obsession with appearance of body parts often muscle size followed by inappropriate compensating behavior.

Answer 496

Dietary approaches to stop hypertension Shown to lower blood pressure in normotensive and hypertensive patients Consists of eating foods high in potassium and low in sodium along with fruits vegetables whole grains and lean meats and dairy

Answer 497

It hydrolyzes triglycerides in blood borne lipoproteins allowing adipose tissue to take up free fatty acids

Answer 498

Hydrolyzes stored triglycerides in adipose tissue to release free fatty acids to be used for energy

Answer 499

Think adiponectin is good for you! It is produced by adipocytes and has anti-atherosclerotic effects and increases insulin sensitivity. It is lower in obesity, insulin sensitivity, metabolic syndromes and type 2 diabetes

Answer 500

Inhibits HSL and activates LPL -> results in more fat storage Stimulates leptin

Answer 501

1 Higher angiotensin expression -> increases blood pressure 2 Leptin is mainly produced in subcutaneous 3 Elaborates most of the IL-6 and TNF-alpha which result in inflammation 4 Believed to be responsible for lower adiponectin in obese and diabetic patients

Answer 502

1 Adipocytes enlarge due to obesity and release more FFAs 2 FFAs lead macrophages to produce more TNF-alpha 3 TNF-alpha activates adipocytes 4 Activated adipocytes increase lipolysis releasing more FFAs, secreting more IL-6 and recruiting more macrophages 5 More macrophages and more FFAs further leads to higher TNF-alpha in a vicious cycle The result is high amounts of inflammation and macrophages in adipose tissue of obese patients. This is adipose dysfunction

Answer 503

High levels of FFAs and TNF-alpha along with low levels of adiponectin in adipose dysfunction lead to greater insulin insensitivity

Answer 504

High triglycerides and low HDL along with hypertension increase the risk of atherosclerosis and result from obesity related adipose dysfunction In addition obese people have high levels of angiotensinogen, ACE and renin which are all parts of the renin-angiotensin aldosterone pathway leading to increased blood pressure Dysfunctional adipocytes produce angiotensinogen and angiotensin 2

Answer 505

Physical activity and calorie restriction Not only does this decrease the amount of adipose tissue and lead to weight loss, this decreases TNF-alpha, IL-6 while increasing adiponectin. All of this works together to decrease inflammation and increase insulin sensitivity even before weight loss occurs

Answer 506

An alarm is placed in the child’s pants that goes off in response to the first drops of urine. In this case the Neutral stimulus is the feeling of a full bladder, the unconditioned stimulus is the alarm noise and the unconditioned response is waking up. Eventually by pairing the alarm to a full bladder for several weeks, children learn to associate the two stimuli and eventually if the alarm is removed, they will wake up to a full bladder alone

Answer 507

This is a form of classical conditioning and follows these steps 1 Learn incompatible response besides fear and anxiety such as deep relaxation (breathing exercise) 2 Create an anxiety hierarchy- rank situations from little fear to a lot of fear 3 Gradually expose the patient to more and more threatening stimuli and allow them to experience each situation long enough until the anxiety subsides Eventually, the situation becomes less threatening

Answer 508

A way to use classical conditioning to create more fear toward a situation For example, you could give an alcoholic something that makes them nauseated each time they drink and eventually the idea of drinking alone will cause them discomfort or fear

Answer 509

1 Controlling the exposure to feared object/situation- sometimes it can be hard to give a small exposure without giving anything bigger for example a phobia of flying 2 Identifying the focus of the fear- for example someone with panic attacks may not understand what sets them off 3 Timing the exposure to feared object- the exposure can’t be too short, it must be long enough for the anxiety to go away 4 Make the exposure challenging enough- for example someone with a social phobia must experience difficult social situations such as someone being rude in addition to positive ones or else they will struggle with those in the real world

Answer 510

1 Shape behavior little by little-instead of offering an award for the perfected final product, small rewards should be offered for smaller steps along the way 2 Frequency of consequences- continuous reinforcement is required in the beginning to acquire the behavior and after that intermittent reinforcement is enough to maintain 3 Timing of consequence- there must be a close temporal link between action and consequence 4 Clarity of consequence- must be clear and specific about the action being reinforced or punished

Answer 511

These patients either do not eat enough or enough variety of foods by mouth to sustain proper growth and development Positive reinforcements could be made for each bite of a non-preferred food such as a bite of a preferred food Negative reinforcement could be used when a disliked food is place close to the child’s face so that they must see and smell it until it is removed when they eat it Punishment could be used such as a firm tone of voice if the child is spitting or acting out in another way Extinction could be used by withdrawing attention and eye contact until the child takes a bite

Answer 512

A severe, chronic condition that: 1 is attributable to mental or physical impairment or a combination 2 is manifested before the age of 22 3 Is likely to continue indefinitely 4 Results in limitations in 3 or more areas of major life activity Self care, Language, learning, mobility, self-direction, economic self-sufficiency, and independent living 5 Reflects a need for support and services that are lifelong or extended duration

Answer 513

Diagnosed by age 18 | IQ below 70 AND deficits in adaptive behaviors (ability to accomplish tasks of daily living)

Answer 514

1Conceptual - ability to understand time, do math, read, write and communicate 2 Social- avoid being tricked or manipulated and follow social rules and expectations 3 Practical- Hygiene, money, technology

Answer 515

1 Persistent deficits in social communication and interaction across multiple contexts 2 Restricted, repetitive patterns of behavior, interests or activities 3 Symptoms present in early developmental period (even if not fully manifested until later) IN the clinic Patients could be sensitive to touch or certain sounds so be aware May engage in self-stimulatory behaviors- don’t tell them to stop May talk excessively about a topic of interest- don’t get frustrated just try to redirect them

Answer 516

Results from brain damage, before during or right after birth Usually affects individuals ability to move, balance or speak In the clinic They may have difficulty with physical movements ie moving limbs or getting onto an exam table They may have difficulty speaking- this doesn’t mean they have an ID Ask if they need assistance before touching or repositioning them

Answer 517

A birth defect in which the spinal column does not close completely 1 Spina bifida oculta- most common and mild form 2 Meningocele- the split creates a sac of nerve fluid on the back 3 Myelomeningocele- spinal cord and nerves enter the sac of fluid- most severe and disabling form In the clinic May have mobility issues Likely to have allergies such as latex May have bowel or bladder incontinence

Answer 518

Most have ID Low muscle tone is common and they often receive physical therapy to improve speech and articulation and other movements In the clinic Low muscle tone may affect their speech but it doesn’t mean they can’t speak or don’t understand so ask them to repeat themselves or say it another way if necessary to understand them Weight is a common problem in Down syndrome so discuss exercise and diet

Answer 519

Genetic condition causing ID, symptoms of autism spectrum disorder, ADHD and anxiety In the clinic Be attentive to anxiety levels and other mental health issues Be aware of common ADHD

Answer 520

1Caregivers are vulnerable and uncertain about future so be positive but don’t make promises about future ability, be aware of financial burdens, give basic information about getting ready for preschool 2 Make sure caregivers take care of their own health as well

Answer 521

1 Need primary healthcare like all other children (well visits) 2 May be uncomfortable or afraid of doctor’s offices so do your best to engage with them and help them be comfortable 3 May need extra time for examinations and procedures

Answer 522

1 They need the conversation about sexual health just like all other teens- may need additional education on this topic 2 May be more likely to engage in risky behaviors 3 Transitions and failure to achieve milestones can be especially difficult 4 Plan for transition to adult care provider

Answer 523

1 Give them normal guidelines for preventive care 2 Be aware of disability-specific risks 3 May have lost access to many services offered through school systems-ask if their needs are being met

Answer 524

1 Parents pass away and caregiver responsibilities may change 2 Especially vulnerable to elder abuse 3 May not fully understand aging and dying- have conversations about end of life decision making with them, family and caregivers being sure to respect their autonomy

Answer 525

Screening is less expensive and administered to healthy populations in order to identify those with a high probability of disease but not to diagnose A diagnostic test is used for diagnosis and only given to those suspected to have the disease

Answer 526

1 Suitable disease- the disease should have serious consequences, be progressive with treatment most effective at earlier stages and it must have a detectable pre-clinical phase 2 Suitable test- must be inexpensive, quick, safe, easy and relatively painless to administer and should have high validity and reliability 3 Suitable screening program

Answer 527

1 Primary- Prevent the disease before its onset 2 Secondary- delay the onset of symptom appearance 3 Tertiary- slow disease progression, alleviate symptoms and prolong life

Answer 528

The time by which the diagnosis of a disease is advanced because of screening. For example, if onset of symptoms would have been 60 but you detect the disease at 55 by screening, the lead time is 5 years

Answer 529

Sensitivity = how many of the people with the disease are characterized as positive. Sensitivity = True positives/True positives + false negatives Specificity = how many people who don’t have the disease are characterized as negative. Specificity = true negatives/true negatives+ false positives Criterion of positivity is the test value determined to represent a positive score As you move the CP in one direction you will improve either sensitivity or specificity but make the other worse so researchers must choose a point that best accomplishes what they want

Answer 530

A measure of the proportion of true results among all results Overall accuracy = True positives + true negatives/ All results

Answer 531

Positive predictive value is a measure of how likely someone who tested positive is to actually have the disease PPV = True positive/True positive + False positive Negative predictive value is a measure of how likely someone who tested negative is to actually be disease free NPV = True negative/True negative + false negative

Answer 532

You prioritize sensitivity any time it is more important to identify all people with a disease than make sure you don’t have false positives. Thus whenever you would rather have a false positive than a false negative you optimize sensitivity. This might occur with a disease that can be transmitted because you want to identify all cases to avoid further transmission You prioritize specificity any time you would prefer to have false negatives over false positives This could be the case with an untreatable, fatal disease because a false diagnosis would cause serious harm to a patient and there is little to gain from knowing that you have the disease since nothing can be done to improve the situation

Answer 533

Low disease prevalence -> higher false positives | High disease prevalence -> higher false negatives

Answer 534

1 Count - Simply the number of people 2 Ratio - Comparison between two groups 3 Proportion - Comparison between one part of a group and the total group to which that part belongs 4 Rates - ratios or proportions that include an element of time

Answer 535

Fixed = permanent membership based on defined event or characteristic Dynamic = transient membership based on being in or out of a state Dynamic is more common and makes things more complicated

Answer 536

Incidence = frequency of new cases within a population I = new cases/population over specific Time period 1 Cumulative incidence = # of new cases/# at risk at beginning of follow up over a specific time period- this works better for a fixed population 2 Incidence rate = # new cases/Sum of disease free person-time over specific time period. Instead of assuming everyone remains part of the group for the entirety of the study, it attempts to account for a dynamic population by counting the amount of time a person was a part of the group during the period of time

Answer 537

1 Add up all the risk periods for each individual in the study - hardest but most accurate method 2 Average number of people in study * duration of study 3 Number of people in the study * average duration per person

Answer 538

A measure of the proportion of the population with the disease over at a time. Includes both new and existing cases] 1 Point prevalence = # of cases /total population at a specific point in time 2 Period prevalence = existing cases + new cases/population at midpoint over a period of time

Answer 539

Prevalence is a function of incidence and duration of disease.

Answer 540

1 Binary- two options 2 Categorical - more than two and fewer than infinity options 3 Continuous- infinite number of options- numerical data 4 Time to event data

Answer 541

1 nominal- no implied order | 2 Ordinal- implied order

Answer 542

Measures of central tendency- mean and median Measures of variability - Range and standard deviation

Answer 543

Mean: 5 Median: 4.5 Standard deviation: Square root(7.67) = 2-3 around 2.8

Answer 544

Normality describes how close the data resembles a normal bell shaped distribution where the mean, median and mode are equal and the curve is symmetrical You could graph the data either in a histogram and see if it looks like a bell curve or in a quantile quantile plot and see if points fall on or near the line of best fit The most accurate way is to do a Shapiro-Wilk test. Null hypothesis is normally distributed so p

Answer 545

Should include the following groupings Ingested proteins Amino acid biosynthesis Both of these feed into the amino acid pool Which feeds into Protein (also feeds back to amino acid pool) Deamination which produces NH4+ and Carbon Skeletons NH4+ feeds into excreted nitrogen Carbon skeletons produce either acetyl coA or TCA cycle intermediates/pyruvate depending on whether they are Ketogenic or glucogenic

Answer 546

It provides precursors to many important nitrogen-containing compounds such as nucleotide bases, heme and creative

Answer 547

Nitrogen balance is the amount of ingested nitrogen - excreted nitrogen. Nitrogen equilibrium is when nitrogen balance = 0. Nitrogen balance can also be positive meaning more nitrogen is entering the body than is leaving or negative meaning more is leaving than is entering In order to maintain adequate nitrogen balance, a person must meet quantity and quality requirements of amino acids meaning they are eating enough total and they are getting a complete complement of essential amino acids

Answer 548

Growth Pregnancy Attempting to gain lean body mass

Answer 549

A negative nitrogen balance occurs when proteins within the body are being catalyzed in high quantities to produce energy and their nitrogen is being excreted in higher levels than the nitrogen being ingested This can result from a lack of protein in the diet or from catabolic diseases such as cachexia which causes a hypercatabolic state

Answer 550

In general nonessential amino acids are much simpler to synthesize and catabolize and require many fewer enzymes. They are also generally glucogenic this may be a reason why the body retains the ability to synthesize them Essential amino acids on the whole are more complex to synthesize and catabolize requiring many enzymes

Answer 551

Cause: genetic deficiency in phenylalanine hydroxylase enzyme which converts phenylalanine to tyrosine Symptoms: Tyrosine becomes an essential amino acid Phenylalanine builds up mostly as phenylpyruvate and phenylacetate these can be toxic to the brain leading to mental disabilities and seizures Treatment: avoidance of phenylalanine (contained in aspartame) Supplementation of tyrosine

Answer 552

Methionine is converted to homocysteine which provides the sulfur to convert serine to cystathionine by the enzyme cystathionine synthetase. Cystathionine is then converted to cysteine by cystathionase 1 Homocystinuria occurs by deficiency of cystathion synthetase and results in cysteine becoming conditionally essential as well as accumulation of homocysteine and methionine 2 Cystathioninuria occurs by deficiency of cystathionase resulting in cysteine being conditionally essential and buildup of cystathionine.This is more benign than homocystinuria

Answer 553

A transamination occurs in which the nitrogen from glutamine is transferred to aspartate to produce asparagine. The enzyme is asparagine synthetase In acute lymphocytic leukemia, leukocytes are deficient in asparagine synthetase and must rely on the extracellular environment to take up asparagine. A common treatment is L-asparaginase which breaks down asparagine in the extracellular environment depriving cancer cells of their only access to asparagine and causing them to undergo cell death

Answer 554

Amino acids undergo transamination where their nitrogens are transferred to alpha ketoglutarate to produce glutamate and alpha ketoacids. Glutamate can then undergo oxidative deamination producing ammonia and alpha ketoglutarate

Answer 555

The purpose is to convert ammonia into urea which is less toxic to be excreted. Ammonia easily crosses the blood-brain barrier and causes damage to neurons. 1 HCO3- + NH4+ -> carbamoyl phosphate Enzyme: Carbamoyl phosphate synthetase 2 Carbamoyl phosphate + ornithine-> citrulline Enzyme ornithine transcarbamoylase 3 Citrulline + aspartate -> argininosuccinate Enzyme: argininosuccinate synthetase 4 Argininosuccinate -> fumarate + arginine Enzyme: argininosuccinate lyase 5 Arginine -> Urea + ornithine Enzyme: Arginase Urea cycle occurs mainly in the liver 1-2 occur in the mitochondrial matrix 3-5 occur in the cytosol

Answer 556

Sharp rises in BUN indicate renal failure since the kidneys are responsible for excreting the urea produced in the liver

Answer 557

Too much ammonia leading to neurological damage Symptoms include: tremors, slurred speech, vomiting, cerebral edema, blurred vision, coma and death Can occur: 1 Congenital- rare mutations to one of the 5 urea cycle enzymes. The earlier in the process the enzyme acts the more severe. Infants show no signs at birth but have symptoms within 24 hours 2 Acquired : can occur as a result of liver cirrhosis (hepatic encephalopathy) or bacterial infection - some bacteria can convert urea back to ammonia leading to both hyperammonemia and kidney stones Can be treated by restricting protein in the diet and supplementing with essential amino acids or by using sodium benzoato or sodium phenylbutyrate which lead other pathways of nitrogen excretion besides urea

Answer 558

``` They are the most hydrophobic ones which resemble fatty acids Isoleucine Leucine Lysine Phenylalanine Tryptophan Tyrosine ```

Answer 559

A medium chain fatty acid with 7 carbons. It produces propionyl coA when oxidized and also can produce a 5 carbon ketone body. It can be used to treat pyruvate carboxylase deficiency and cptii deficiency

Answer 560

The ratio of CO2 exhaled / O2 inhaled during metabolism of a certain food Carbs = 1 Protein = 0.8 Fat = 0.7

Answer 561

1 Acinar cells- exocrine secretions make up vast majority of mass of pancreas 2 Islets of langerhans- endocrine secretions (1-2% of pancreas mass) Within islets, Alpha cells- glucagon Beta cells- insulin Gamma cells- somatostatin Others

Answer 562

They are exact opposites Insulin- activates uptake of glucose from blood at target cells in response to high blood glucose levels and is produced in beta cells Glucagon- activates release of glucose in response to low blood glucose and is produced in alpha cells

Answer 563

1 Skeletal muscle 2 Adipocytes 3 Liver

Answer 564

1 Insulin binds to its receptor (a pre dimerized RTK) 2 Receptor activates IRS1 (insulin receptor substrate 1) 3 IRS1 activates the PI3 kinase pathway 4 Vesicles containing GLUT4 (glucose transporter) are send to the plasma membrane increasing glucose uptake

Answer 565

Insulin is a small peptide hormone made up of an A and a B chain which are bound together by disulfide linkages 1 Translated to preproinsulin containing A, B and C chains along with signal peptide into ER 2 Signal peptidase removes signal peptide to form proinsulin 3 In ER proinsulin folds and disulfide linkages form between A and B chains 4 In secretory vesicles, the protein is cleaved so that the C chain is removed producing mature insulin

Answer 566

Part of the pro hormone which is removed during the formation of mature insulin. It is secreted along with insulin and produced in amounts equal to insulin. It is also much more stable than insulin and so its concentrations give clinicians an idea of the amount of insulin that is being produced

Answer 567

Insulin is stored in secretory vesicles or storage granules In these vesicles, they form a quaternary structure consisting of 3 dimers around a Zn ion where His from B chain of insulin is interacting with Zn ion

Answer 568

The increased blood flow allows both the ability to sense glucose levels in the blood and to quickly distribute insulin into circulation.

Answer 569

GLUT2 transporters bring glucose into the cell-> high glucose means more glycolysis -> high glycolysis means more ATP -> ATP closes K+ channels leading to more + charge within the membrane -> voltage gated calcium channels open -> Ca2+ leads to secretion of insulin

Answer 570

Insulin secretion occurs in 2 phases 1- rapid, transient secretion 2 - slow, sustained secretion This occurs because there are two pools of storage granules. Rapid phase occurs as a result of secretion from vesicles near the cell surface and slow, sustained secretion results from vesicles stored near the center of the cell

Answer 571

Both transport glucose into cells GLUT4 transports glucose into cells in response to insulin secretion GLUT2 transports glucose into beta pancreatic cells as a part of glucose sensing prior to glucose release

Answer 572

Glucagon consists of a single short peptide chain that creates an alpha helix It is synthesized as a preprohormone which contains insulin along with other chains which serve other functions. The preprohormone is cleaved differently in different tissues in the body but in the pancreas it is cleaved in a way that separates the glucagon hormone from the other chains. In other tissues, the glucagon hormone forms part of a larger protein

Answer 573

Low glucose in the blood triggers voltage gated opening of calcium channels in alpha cells of the pancreas. The influx of calcium causes vesicles containing glucagon to fuse with the membrane allowing release of glucagon

Answer 574

Randomized poor children into two groups, 1 receiving daily childcare for the first 5 years of life in addition to other services and the other receiving all other services but not childcare. They followed those children over more than 40 years and tracked the differences between the two groups. They found marked differences in social and health outcomes including lower blood pressure, cholesterol, metabolic syndromes and CV risk scores in the childcare group. The childcare group had better outcomes in all areas. This illustrates the importance of the environment especially during the early years of development

Answer 575

Compared children born during the famine when rations were limited to 400-1000 Calories per day (far less than a pregnant mother needs) to children born before and after that time. In addition to low birth weight, neurological and other health issues were more common in children born to malnourished mothers during the famine. These included CVD, glucose-insulin disorders, obesity, renal dysfunction, airway disease and breast cancer. This showed that the circumstances facing the pregnant mother affect the baby and can have long-lasting effects

Answer 576

1 Modifications of DNA activity Methylation 2 Histone modifications Acetylation, methylation, phosphorylation, etc. 3 Modifications of micro-RNA MiRNAs downregulate translation of specific mRNA transcripts

Answer 577

Honey bees are generally docile while killer bees are much more aggressive. Researchers placed honey bee larvae with killer bees and vice versa and then measured their behavior. Honeybees raised around killer bees acted just like killer bees and killer bees raised with honey bees acted just like honeybees. Further when DNA microarrays were used to measure expression, it was found that expression had been changed in both cases to match the expression of the bees with which they were raised. This shows how environmental factors or experiences can alter DNA expression leading to dramatic changes in behavior/life course

Answer 578

The midbrain which controls the emotions, fear and stress among other things develops first while the frontal cortex develops much more slowly and will not be completely developed until after adolescence. The frontal cortex includes areas involved in planning, calculating and importantly impulse control. Children often throw temper tantrums and have difficulty controlling emotions as a result of a developed midbrain but immature frontal cortex. In order to handle emotions and stress in a way that will be less damaging, a child must have a well developed frontal cortex

Answer 579

Though some limited stress can be positive, both of these refer to negative stress. The difference between the two is in how developed the frontal cortex of the brain is and how well the child can handle the stress. If a child is developed enough to handle the stress in a way that is minimally harmful than it is tolerable but if they cannot, then it is toxic

Answer 580

Adverse childhood experiences. These are specific events or experiences known to cause a lot of harmful stress on a child. People with a high number of ACEs in childhood often develop social, emotional and cognitive impairments, they often engage in health-risk behaviors, they are more susceptible to diseases and they often die early

Answer 581

Baby Rats were removed from their parents and then returned after a short time. Some parents licked and groomed their rats while others did not. The lickers and groomers showed a rapid decrease in stress hormones after being returned while those that did not receive licking and grooming did not. Also over the course of their lives, rats receiving licking and grooming were healthier in a variety of ways. This was true of all rats receiving licking and grooming whether it was from their biological parent or not. This teaches us that certain behaviors on the part of parents or other caregivers are important for helping children respond to stress and these behaviors can have long-lasting and far-reaching affects on the child’s life

Answer 582

``` 1 Breastfeeding 2Back and forth communication 3 Stimulating environment 4 Daily routine 5 Teaching through play 6 Disciple aimed at teaching 7 Practice social-emotional skills ```

Answer 583

Focused (point of care) is done by a clinician at the bedside with the purpose of answering a specific question Comprehensive is generally performed by a technologist and interpreted by an imaging specialist and seeks to get a more thorough view of an entire system

Answer 584

1 Black or anechoic Fluid and artifacts such as posterior acoustic shadowing 2 Gray or hypoechoic Medium to low density tissues and some artifacts 3 White or hyperechoic High density tissues and air

Answer 585

1 Near field- the top-represents more superficial 2 Far field- the bottom usually more deep tissues 3 Leading edge- the side closest to the indicator (often the left) 4 Receding edge- the side farthest from the indicator (often the right)

Answer 586

The conversion between electrical and mechanical energy. Ultrasound uses crystals that vibrate to produce sound waves (mechanical energy) from electrical energy. The waves that bounce back off body tissues to the ultrasound machine are then converted back into electrical energy so they can be understood

Answer 587

Uses the Doppler effect to estimate movement of particles such as blood cells based on the change in frequency caused when they run into each other.

Answer 588

1 Fan- change the angle of the probe perpendicular to the indicator without moving the probe 2 Sweep- move the probe perpendicular to the indicator without changing the angle 3 Rotate 4 slide - move the probe parallel to the indicator without changing the angle 5 rock = Change the angle of the probe parallel to the indicator without moving it

Answer 589

1 Intermediate filaments- strong, flexible rope like structure thicker middle thickness. Mainly protects cells from mechanical stresses 2 Microtubules- stiff hollow rod like structures important in transport of cargo, formation of cilia and flagella and cell division 3 Actin- thin fibers with a wide variety of structures and functions regulated by actin binding proteins

Answer 590

A mesh on the inside of the nuclear envelope made up of intermediate fibers

Answer 591

Plaque like structures that anchor intermediate filaments to the plasma membrane

Answer 592

They form a network surrounding the nucleus which extends out to the periphery of the cell

Answer 593

They are made up of alpha helical monomers with coil together to form dimers called coiled-coil dimers. 2 dimers come together in a staggered way to form a tetramer. 8 tetramers are arranged side by side to form a bundle and bundles arrange end to end to create filaments with no polarity.

Answer 594

1 Keratin filaments- epithelial cells 2 Vimentin and vimentin related filaments- connective tissues, muscles, glial cells 3 Neurofilaments- neurons 4 Nuclear lamins - in the nucleus of all cells

Answer 595

Caused by mutations to skin specific keratin genes causing the skin to be sensitive to minor mechanical stress such that even small amounts of mechanical pressure cause skin blisters

Answer 596

Caused by a rare mutation to the gene encoding nuclear lamin A. The nuclear lamin therefore doesn’t form correctly and the nucleus is irregularly shaped and chromatin, gene expression and division are affected. Symptoms are prematurely aging: limited growth, wrinkling of skin, loss of hair, CV and kidney problems, musculoskeletal degeneration. Symptoms appear in first few months of life and the lifespan is generally into the teens

Answer 597

Alpha and beta tubulin form a dimer. These timers stack end to end to form a protofilament. 13 protofilaments associate side by side to form a hollow tubed structure which is a microtubule. One end has an alpha tubulin while the other has beta tubulin. Beta tubulin end is the + end where tubulin are incorporated more rapidly and the alpha end is the - end where tubulin are incorporated more slowly

Answer 598

Microtubules extend from outward from an organizing center called a centrosome which is located near the nucleus. A centrosome is made up of two centrioles and a matrix made up of hundreds of gamma tubulin rings. The - ends of microtubules become embedded in the gamma tubulin rings and the + ends are left exposed to grow outward

Answer 599

Centrioles are made up of perpendicular arrays of short microtubules. They are contained within the centrosome but in most cells their function is unknown. In ciliated cells, centrioles called basal bodies act as organizing centers for cilia. In dividing cells, 2 centrioles act as organizing centers for the mitotic spindle

Answer 600

Microtubules can rapidly polymerize or depolymerize at their + end and they undergo periods of each

Answer 601

Tubulin dimers bind to GTP before incorporating into the microtubule. Eventually this GTP is hydrolyzed to GDP. While GTP bound, dimers bind tightly to neighboring dimers however, once GTP is hydrolyzed, they bind less tightly and if exposed can fall off the microtubule. As long as dimers are being added quickly, no GDP bound dimers are exposed and so polymerization continues however if dimers cease to be added, GDP bound dimers become exposed and depolymerization occurs

Answer 602

1 Taxol- stabilizes microtubules 2 Colchicine- prevents polymerization 3 Vinblastine- prevents polymerization Microtubules are required for dividing cells such as cancer cells so cancer cells will be destroyed by lack of microtubules

Answer 603

Kinesins- move toward the + end or the outside of the cell Dyneins move toward the - end or inside of the cell They both have 2 head groups which bind to microtubules and walk along them. Their tail groups differ and bind to cargo

Answer 604

Cilia and flagella are made up of microtubules arranged in a 9+2 array so that there are 9 microtubule doublets around the outside circled around 2 single microtubules in the center. The heads of dyneins bind to one doublet while their tails bind to an adjacent doublet. Thus walking of the dyneins leads to movement of the cilia or flagella

Answer 605

Actin monomers bind together to form a thin 2 stranded helix structure with a + end (rapid growth) and a - end (slower growth) Monomers are bound to ATP which causes them to bind tightly to other actin monomers but when they become part of the polymer ATP is hydrolyzed to ADP causing it to bind less tightly and allowing depolymerization.

Answer 606

1 Microvilli 2 Stress fibers- contractile fibers within non muscle cells 3 Transient cellular projections 4 Contractile ring- separates dividing cells The presence of different binding proteins determines the shape that they will take

Answer 607

Cilia- Long and wide, made up of microtubules, motile Microvilli- Smaller, made of actin, do not move

Answer 608

Because actin is not attached to an organizing center at either end, polymerization and depolymerization can occur at either end. Treadmilling occurs when depolymerization occurs at the - end while polymerization occurs at the + end such that monomers move through the filament but its size doesn’t change

Answer 609

Actin can allow cell migration by creating projections when its + end is facing the plasma membrane. These projections adhere to surroundings and allow the cell to drag itself forward. 1 Lamellipodium- broad, thin sheets of membrane with a dense meshwork of actin within 2 Filipodium- long, stiff finger like projections with parallel actin filaments

Answer 610

Myosin- many different types, all have actin-binding head and different tail shapes and walk along actin with their heads. Myosin II is involved in contraction. It can bind tail to tail and in muscle cells in forms thick filaments made up of myosin. Myosin II is arranged so that when each myosin moves toward the + end of the actin to which it is bound, it brings them together causing contraction

Answer 611

They are important proteins regulating actin organization. They activate downstream actin binding proteins which determine the shape and function of actin within the cell

Answer 612

A broad spectrum of disorders caused by mutations to muscle specific actin. This can result in heterogenous symptoms of muscle weakness which can be severe enough to cause neonatal death or can be mild muscle weakness in adults

Answer 613

Graph insulin secretion offer time after a meal vs after intravenous glucose infusion. The incretin effect is the difference in the amount of insulin secreted after a meal and the amount secreted after intravenous injection. After a meal insulin is higher. The incretin effect is decreased in diabetic patients.

Answer 614

Glucose levels are increased much more than normal patients after a meal Insulin levels rise much higher after a meal in normal patients than in diabetic patients Glucagon levels fall after a meal in normal patients but do not fall nearly as much in diabetic patients

Answer 615

GLP-1 - L-cells of the ileum and colon- can be used therapeutically GIP- Kcells of jejunum cannot be used therapeutically Stimulate glucose dependent insulin secretion Suppress glucagon secretion Slows gastric emptying Reduces food intake Improves insulin sensitivity Long term: may improve beta cell mass and function

Answer 616

Enzyme that cleaves GLP-1 to inactive form DPP4 inhibitors are an option in treatment of type 2 diabetes since they increase levels of GLP-1

Answer 617

1 GLP-1 agonists 2 DPP4 inhibitors GLP1 agonists must be administered intravenously while DPP4 inhibitors can be taken orally. In addition, GLP-1 agonists reduce gastric emptying and promote weight loss while DPP4 inhibitors do not. They also cause nausea which is not observed in DPP4 inhibitors

Answer 618

Normally, insulin is suppressed but in type 1 diabetes there is no insulin in the first place Normally glucagon is released in response but not in type 1 diabetes Epinephrine is normally released after glucagon but in type 1 diabetes it is the first defense and eventually may be lost (hypoglycemia-associated autonomic failure) Cortisol and growth hormone are the last thing released to combat hypoglycemia in both cases

Answer 619

Occurs mainly in type 1 diabetes and only rarely in type 2. Lack of insulin -> intracellular starvation -> release of Counter-regulatory hormones -> increase severe increase in blood glucose, ketones and prostaglandin I2 and E2 Body cannot use glucose for energy even though it is in the blood leading to the breakdown of fat for ketone bodies which can become toxic in high concentrations

Answer 620

``` Nausea/vomiting Thirst/polyuria Abdominal pain Shortness of breath Findings Tachycardia Hypotension/dehydration Respiratory distress Abdominal tenderness Lethargy ```

Answer 621

1 Glucagon 2 Catecholamines 3 Glucocorticoids 4 Growth hormone

Answer 622

1 Liraglutide | 2 Exenatide

Answer 623

In type 1, an autoimmune disorder attacks pancreatic beta cells so that no insulin is produced. Type 1 diabetics therefore all need insulin and don’t respond to some of the other treatments used for type 2 diabetes. It is also generally diagnosed in childhood to early adulthood. Symptoms are often severe such as hypoglycemia and diabetic ketoacidosis Type 2 diabetes begins with insulin resistance and usually progresses to a point where not enough insulin is being produced. It is often diagnosed later in life than type 1 diabetes and has a stronger connection to diet and lifestyle factors than type 1 symptoms are often too mild to be noticed until permanent damage is done

Answer 624

``` Polyuria Polydipsia Blurry vision Fatigue Hunger Weight loss In an emergency: Dizziness/confusion Vomiting/abdominal pain ```

Answer 625

Method. Healthy. Prediabetes. Diabetes 1 Fasting blood glucose <100. 100-125. 125+ 2 2 hr oral glucose tolerance test <140. 140-199. 200+ 3 HbA1c. <5.7. 5.7-6.5. 6.5+

Answer 626

Overweight (BMI 25+) and additional risk factors Family history High-risk race/ethnicity (black, latino, Asian, Native American, Pacific Islander) Physical inactivity Hypertension etc Or Over the age of 45 every 3 years (more often depending on initial results)

Answer 627

1 Metformin- gold standard first tried. Decreases gluconeogenesis in the liver 2 Sulfonurea- causes pancreas to produce more insulin 3 TzD - makes muscle and fat more sensitive to insulin 4 DPP4 inhibitors - increase the concentration of natural GLP-1 5 GLP-1 analogues- adds additional GLP-1 which stimulates insulin after meals, slows gastric emptying, reduces glucagon after meals, and makes you feel full 6 SGLT-2 inhibitors- decrease renal reabsorption glucose causing glucose to be lost in the urine GLP-1 analogues, DPP4 inhibitors and SGLT-2 inhibitors have been shown to improve cardiac outcomes

Answer 628

1 Always in type 1 diabetes 2 Type two diabetes that is not well controlled by metformin and other drugs or where contraindications to those other drugs exist 3 Type 2 diabetes with severe symptoms

Answer 629

1 Basal insulin- slow and long acting 2 Bolus insulin- rapid and short acting (taken with meals) 3 Pre mixed insulin

Answer 630

``` Blood glucose <70 Causes Missed meals/eating less Over exercising Too much medication: high insulin doses Symptoms: Shaking, sweating, dizziness, hunger, tachycardia, impaired vision, fatigue, headache Treatment: Consume 15 grams of glucose or carbs Check glucose again after 15 minutes Repeat if necessary until resolved ```

Answer 631

``` Macrovascular = injury to large blood vessels Heart: Myocardial infarction heart failure Brain: Stroke Cognitive impairment Extremities: Ulcers Amputations Aneurysms ```

Answer 632

``` Microvascular = injury to small vessels Eye: Retinopathy Cataracts Glaucoma Blindness Kidney: Nephropathy Kidney failure Nerves: Neuropathy Amputation ```

Answer 633

Glucose 6 phosphate can be converted to fructose 6 phosphate to continue glycolysis or it can be converted to ribose 5 phosphate a precursor to nucleotide synthesis or it can be converted to glucose 1 phosphate a precursor to glycogen synthesis Pyruvate can be converted to Acetyl coa for TCA cycle, lactate in anaerobic respiration, alanine or oxaloacetate for gluconeogenesis Acetyl coa can enter the TCA cycle but it can also be converted to fatty acids, cholesterol or ketone bodies

Answer 634

1 Allosteric interactions- binding away from the active site changes the activity of an enzyme 2 Covalent modification- phosphorylation etc. 3 Adjustment of enzyme levels 4 Compartmentation- enzymes present in only certain areas of a cell with specific conditions 5 Metabolic specialization of organs

Answer 635

1 Binding to the receptor activates adenylyl cyclase leading to cAMP formation 2 cAMP activates protein Kinase A 3 PKA activates phosphorylase kinase and inactivates glycogen synthase by phosphorylation 4 Phosphorylase kinase activates glycogen phosphorylase b turning it to glycogen phosphorylase a 5 Glycogen phosphorylase a breaks down glycogen

Answer 636

``` Skeletal muscle: Increased glycolysis Increased glycogenolysis Increased triglyceride utilization Decreased glycogen synthesis Liver: Increased glycogenolysis Increased gluconeogenesis Decreased glycolysis Decreased glycogen synthesis Decreased fatty acid synthesis Adipose: Increased lipolysis Decreased triglyceride utilization ```

Answer 637

The rate limiting and committed step of glycolysis is conversion of fructose 6-p to fru 1,6 bisphosphate by phosphofructokinase This step is activated by AMP Fru 2,6 bisphosphate (produced from 1,6 bisphosphate) Inhibitted by ATP Citrate

Answer 638

Enzyme isoforms are different in each location and are regulated differently Phosphofructokinase 1 is on the same protein as the phosphatase that drives the reverse reaction (fru-1,6Bisphosphatase) Liver: F26Bphosphatase is activated by PKA in response to catecholamines Skeletal muscle PFK1 and F26Bphosphatase are activated by levels of substrate alone Heart: PFK1 is activated by PKA in response to catecholamines

Answer 639

``` Skeletal muscle: Increased protein degradation Adipocytes Increased lipolysis/expression of lipases Liver Increased gluconeogenesis Increased glycogen synthesis ``` Glucocorticoids respond to chronic stress by preparing the body to be able to respond rapidly to acute stress at a later time

Answer 640

1 Alcohol dehydrogenase converts ethanol to acetaldehyde which is then converted to acetate each step reduces 1 NAD+- this is the primary process 2 CytP450 converts ethanol to acetaldehyde by a more complex process requiring one NADPH. Acetaldehyde will ultimately be converted to acetate- this process generates ROS and is induced only by heavy drinking

Answer 641

1 Increased NADH from alcohol metabolism leads to conversion of pyruvate to lactate this leads to lactic acidosis as well as the shutdown of gluconeogenesis which requires pyruvate as a substrate leading to hypoglycemia. 2 Increased NADH leads to higher levels of G3P which feeds into production of triacylglycerols. This combined with the effect of low NAD+ blocking fatty acid oxidation leads to hyperlipidemia 3 High NADH also drives the TCA cycle to run in reverse leading to high levels of Acetyl coa which is converted to ketone bodies producing ketoacidosis

Answer 642

Often busy with little time for meal planning and preparation Food as comfort, fuel, tradition, celebration, enjoyment, etc. Increased eating out today Exploration of fad diets Growth is completed and goal is maintenance of lean mass and good health Risk of chronic diseases such as obesity diabetes and hypertension are up from earlier in life

Answer 643

``` Women: 25-35 Kcals/kg Men: 25-45 Kcals/kg Fats = 30% Carbohydrates = 50% Proteins = 20% Key nutrients Fiber, folate, Calcium, Iron, Magnesium, vitamin D ```

Answer 644

Rapid growth Increasing in fine motor skills Increases in independence over what they put in their mouth Often show strong likes and dislikes Development of healthy eating habits and food preferences during this time is essential for greater health later in life

Answer 645

``` 70-90 Kcals/kg Varies dependent on activity level and energy needs Protein 5-20% Fats 25-35% Carbs 45-65% ``` ``` Key nutrients Iron Zinc Calcium All of these needed for growth ```

Answer 646

More independence with food choices but for the most part parents still provide options Constantly growing Nutritional needs and growth rate vary from child to child Overweight and obesity becomes more of a problem

Answer 647

``` 70-90 Kcals/kg Must be enough to promote growth but not allow excess weight gain Carbs: 45-65% Fat 25-35% Protein 10-30% ``` ``` Key nutrients Calcium Iron Vitamin D Zinc ```

Answer 648

``` Rapid growth and development Psychologic and cognitive transformation Puberty Lean mass deposition Sexual maturity erratic eating patterns Some risks of eating disorder behavior and body image concerns Overweight and obesity in adolescents is also on the rise ```

Answer 649

47-65 Kcals/kg depending on gender and other factors Carbs: 45-65% Fat: 25-35% Protein: 10-30% Key nutrients Calcium Iron Folic acid

Answer 650

Time of uncertainty- retirement, lack of respect/purpose, isolation, diseases etc Body is in decline Lower BMR Loss of muscle mass

Answer 651

``` 20-35 Kcals/kg Decreased from adulthood Carbs: 45-65 Fats: 30% Protein 10-20% ``` ``` Key nutrients Vitamins A, D Calcium Iron Fiber Avoid Cholesterol Sodium Sugars Alcohol Saturated fat ```

Answer 652

1/3 of pregnancies end in spontaneous abortion | 40-50% of these are chromosomal abnormalities

Answer 653

FERTILIZATION occurs usually in the uterine tube After about 30 hours CLEAVAGE begins to producing early embryonic cells called BLASTOMERS while the zygote travels toward the uterus in the uterine tubes After 3-4 days as the embryo is reaching the uterus it reaches the 12-32 cell stage and becomes a MORULA the morula is organized into inner cell mass which will become the embryo and the outer cell mass which will become the fetal component of the placenta After 4 days the morula becomes a BLASTOCYST when it absorbs fluid creating a BLASTOCYST CAVITY At this point the inner cell mass gathers on one end of the blastocyst and becomes the EMBRYOBLAST while the outer cell mass surrounds the embryoblast and the blastocyst cavity and is called the TROPHOBLAST Soon after arriving at the uterus near the end of week 1, the embryo attaches to the posterior or anterior uterine wall

Answer 654

1 Sperm penetrates corona radiata 2 Sperm penetrates zona pellucid a- at this point the zona pellucida changes to not allow any other sperm to penetrate 3 Fusion of cell membranes of sperm and oocyte and fusion of nuclei

Answer 655

The early cell divisions create smaller and smaller cells that remain inside the zona pellucida

Answer 656

The following should be shown: Trophoblast- cells surrounding the outside of the blastocyst Embryoblast- clump of cells at one end of the blastocyst Blastocyst cavity Embryonic pole- side with the embryoblast Abembryonic pole side without the embryo

Answer 657

Just after implantation into the uterine wall, the trophoblast differentiates into CYTOTROPHOBLAST outer layer of the blastocyst and the SYNCYTIOTROPHOBLAST the part directely embedded in the endometrium of the uterus Around day 8, the embryoblast differentiates into the EPIBLAST columnar cells on the external side and HYPOBLAST cuboidal cells on the internal side facing the blastocyst cavity. at this point it becomes known as the BILAMINAR EMBRYONIC DISC. Next, fluid fills in the space between the epiblast and the cytotrophoblast to form the AMNIOTIC CAVITY and epiblast cells migrate to surround this cavity. New tissue forms within the trophoblast cavity called the EXTRAEMBRYONIC MESODERM which then separates into 2 layers with a space between called the CHORIONIC CAVITY which separates the embryo from the outer wall of the blastocyst which is now called the CHORION Around day 8, Hypoblast cells proliferate and migrate once to form the PRIMARY YOLK SAC the membrane of which is known as HEUSER’S MEMBRANE. Later around days 12-13, the hypoblast cells migrate again to form the DEFINITIVE YOLK SAC which displaces the primary yolk sac which now becomes a collection of vesicles at the abembryonic end. At this point, the embryonic disc is suspended in the middle of the chorionic cavity held only be a thin extension of extraembryonic mesoderm called the CONNECTING STALK

Answer 658

An embryo that implants outside of the uterus most commonly in the uterine tubes but sometimes also in the abdomen or other areas. It can be life threatening for the mother because it could rupture important blood vessels as the embryo grows Symptoms: Abdominal pain Vaginal bleeding Treatment: Medications or surgical intervention to interrupt the pregnancy

Answer 659

``` Should include: Connecting stalk CYTOTROPHOBLAST Syncytiotrophoblast Epiblast Amniotic cavity Hypoblast Definitive yolk sac Chorionic cavity Remnants of primary yolk sac ```

Answer 660

1 Trophoblast differentiates into two layers (cytotrophoblast and syncytiotrophoblast) 2 Embryoblast differentiates into epiblast and hypoblast 3 Extraembryonic mesoderm divides into 2 layers 4 Two cavities form - amniotic cavity and chorionic cavity

Answer 661

Gastrulation is the process by which the 3 germ layers are formed from the epiblast in the 3rd week of embryonic development First a part of the epiblast thickens to form the PRIMITIVE STREAK which eventually invaginates and epiblast cells migrate toward it, through it and away from it on the other side. Those cells which displace the hypoblast will form the ENDODERM those that form on top of that are the MESODERM and those that don’t migrate through the primitive streak and remain on top will become the ECTODERM

Answer 662

``` 1 Nervous system 2 Epidermis 3 glands within the hypodermis 4 Sensory epithelial or eyes ears nose and pituitary 5 mammary glands ```

Answer 663

``` 1 Connective tissue 2 Cartilage and bone 3 muscles 4 heart 5 vasculature 6 kidneys 7 gonads 8 spleen 9 Suprarenal cortex ```

Answer 664

``` 1 Epithelial lining of digestive and respiratory tracts 2 thyroid and parathyroid 3 thymus 4 liver 5 pancreas 6 epithelial lining of urinary bladder ```

Answer 665

1 Notochord formation 2 Neurulation 3 Differentiation of mesoderm 4 Body folding

Answer 666

Days 17-18 Cells extend along the midline from the primitive node toward the cranial end of the embryo forming a hollow tube called the NOTOCHORDAL PROCESS Around day 20, the notochordal process fuses with the endoderm to form the NOTOCHORDAL PLATE which is flattened and connected to the endoderm on both ends The notochordal plate then pulls away from the endoderm folding in on itself until it detaches to from a solid cylinder called the NOTOCHORD

Answer 667

The NOTOCHORD induces cells above it in the ectoderm along the midline to thicken forming the NEURAL PLATE The neural tube invaginates to create the NEURAL GROOVE which has NEURAL FOLDS on each side The neural folds eventually come together starting at the midline and fuse forming a hollow tube of cells called the NEURAL TUBE closure of the neural tube begins at the midline and progresses in both directions until openings are left only at the ends, called the CRAINIAL NEUROPORE and the CAUDAL NEUROPORE respectively. These eventually close on day 25 and 27 respectively completing neurulation

Answer 668

They originate at the lateral edges of the neural plate and separate during neurulation to migrate and form a variety of cells

Answer 669

The mesoderm differentiates into 3 types 1 Paraxial mesoderm- thickened plate nearest to the midline which will eventually form somites which are balls of mesoderm cells along the midline that eventually form major mesoderm structures 2 Lateral plate mesoderm- thin layer of mesoderm farthest laterally which will eventually split into 2 layers (visceral and somatic) and surround organs of the body cavity 3 Intermediate mesoderm- Between lateral plate and paraxial mesoderm and will eventually form much of urogenital system

Answer 670

Body folding is driven by differential growth in different areas of the embryo. Occurs in two planes 1 Caudal and Cranial folding where the caudal and cranial aspects fold in together to form the normal embryonic position 2 Lateral folding- the lateral edges of the embryo fold ventrally until they come together and the 3 layers fuse with the same layer from the other side turning the embryo from a disc shape into a cylinder shape

Answer 671

Cardiovascular complications

Answer 672

1 Spina bifida - caudal NEUROPORE | 2 anencephaly- cranial NEUROPORE

Answer 673

``` Cannot Ethnicity Income Family history Higher birth weight Advancing age High blood pressure Can Overweight/obese Sedentary lifestyle Sleep patterns Smoking/alcohol ```

Answer 674

Normal -> Prediabetes -> Diabetes -> Complications -> Disability/death Primary takes place in Normal and prediabetes to prevent onset of diabetes Secondary takes place during diabetes but before the onset of complications in order to prevent/delay onset of complications Tertiary takes place after complications have begun to slow the progression of complications toward disability and death

Answer 675

Recruited a group of patients at high risk of type 2 diabetes based on being prediabetic and overweight or obese They were randomized into 1 of 3 groups 1 Lifestyle intervention- received nutrition/health classes and were helped to achieve the goal of 7% weight loss to be achieved by calorie restriction 1200-1800 Calories per day with less than 25% coming from fat and exercise (150 minutes per week) 2 Metformin group 3 Placebo Metformin group = 31% reduction in risk of T2DM Lifestyle group = 58% Further, metformin was only effective in patients with stage 3 obesity all other BMI categories were not helped by metformin but were significantly aided by lifestyle change Even after 10 years and although many lifestyle participants gained back much of the weight they still had lower risk of T2DM or delayed onset by 4 years

Answer 676

16% reduction in risk

Answer 677

Recruited overweight and obese patients with T2DM to be randomized into a lifestyle intervention group or usual care group The lifestyle intervention group received meal replacements for calorie restriction, 75 minutes per week of exercise and optional pharmacotherapy to lose 7-10% of body weight Lifestyle intervention group showed lower a1c lower blood pressure but no change in LDL cholesterol. Overall CV risk factor score was reduced. In long term assessments, many participants gained weight back and raised a1c’s somewhat but improvements remained in blood pressure, a1c and HDL cholesterol after 4 years

Answer 678

Yes | One study reported that 73.5% of patients lowered mediations in lifestyle group compared to 26.4 in standard care group

Answer 679

1 Dietary consultation-Medical nutrition therapy (nutrition prescriptions) 2 Behavioral modification 3 Increased physical activity 4 weight loss

Answer 680

There isn’t enough evidence to suggest that one diet is best What works for the individual is best. In general low saturated fats and complex carbohydrates are good things along with avoidance of added sugar. The most important part is total energy intake

Answer 681

``` Compliance = how well a person’s behavior matches a medical advice Adherence = how well behavior corresponds to recommendations from provider BASED ON SHARED DECISION MAKING ```

Answer 682

1 Intentional 2 Unintentional-often caused by forgetfulness or carelessness or confusion 3 Chronic 4Acute 5 Cost-related- includes lowering doses to ration expensive medications

Answer 683

Overuse, underuse, misuse or erratic use of insulin Infrequent blood glucose testing Failure to attend medical appointments Poor tracking or record keeping

Answer 684

Teenagers They are seeking independence and rebelling against authority often They have more short term goals Peer influences and less parental involvement in their lives

Answer 685

Overuse of insulin to allow increased eating Skipping meals to avoid insulin administration Diabulimia- avoiding insulin to lose weight

Answer 686

Five factors affecting adherence 1 Susceptibility- what do they believe about risk of the illness 2 Severity- how serious are the consequences of the illness or of non-adherence 3 Benefits- are there immediate benefits 4 barriers 5 Cues- things that prompt action Intervention should be based on which of these factors is most prominent in causing non-adherence

Answer 687

Interaction between behavior, personal factors and external environment come together to influence adherence Intervention should involve skill building and self-advocacy

Answer 688

``` Factors affecting adherence: 1 Attitude 2 Subjective norm- someone else would like this to happen 3 motivation 4 perceived behavioral control ``` Assess and address motivation and perceived control for intervention

Answer 689

Describes the stages individuals go through in the process of changing a behavior 1 Precontemplation- no awareness or desire to change 2 Contemplation- beginning to think about changing 3 Preparation- makes a plan 4 Action 5 Maintenance For an intervention assess which stage they are in and give them resources to help them in that stage and toward the next one

Answer 690

1 Education- helpful initially but usually not enough on its own 2 Organizational- simplify regimens, change the way care is delivered, improve patient doctor relationship 3 Behavioral- assess barriers and encourage incentives

Answer 691

A model where the patient is more responsible and empowered over their own care with the provider as a guide who receives input from the patient in order to help them design a daily management plan Requires providers to not blame patients, avoid showing frustration and seek to build rapport with the patient Research suggests this is the best form of care

Answer 692

FFA’s go to the liver and the skeletal muscle generally Liver Cause increased fatty acid oxidation leading to increased gluconeogenesis Muscle Increased fatty acid oxidation results in decreased glucose utilization These factors along with the fact that FFA’s can lead to insulin resistance mean that higher FFA’s makes hyperglycemia more likely

Answer 693

1 Central obesity 2 Acanthosis Nigerians (darkened, thickening of skin) 3 Hypertension and dyslipidemia 4 Metabolic Syndrome Metabolic syndrome = central obesity + 2 or more of the following: Raised triglyceride levels Reduced HDL High BP Raised Fasting glucose

Answer 694

Insulin resistance begins in prediabetes but early on, the body responds by just making more insulin to counteract. Eventually insulin secretory defects progress to a state of inadequate secretion. By the time of diabetes diagnosis, 50% of beta cell mass is lost Amyloid (co-secreted with insulin) deposits in islet cells) Elevation of FFA’s worsens beta cell function

Answer 695

1 MODY- genetic defects of insulin secretion 2 Genetic disorders of insulin action 3 Pancreatic disorders- ex pancreatitis 4 Endocrinopathies- ex- cushing’s hyperthyroidism 5 Drug-chemical induced- ex glucocorticoids 6 Infections 7 Gestational 8 Immune mechanisms 9 Other genetic syndromes- Down syndrome, klinefelter’s etc.

Answer 696

Placental hormones such as human placenta lactogen promote insulin resistance in order to increase nutrient supply to the fetus Patients are at higher risk for T2DM afterwards

Answer 697

Hyperglycemia associated with critical illness in patients who have not been diagnosed with diabetes prior. Examples: trauma and burns. May be a result of factors such as cortisol, epinephrine, glucagon, growth hormone, gluconeogenesis and glycogenolysis being more common in these patients. SHould be treated acutely and may or may not be reversible after critical illness

Answer 698

Prohormone convertase

Answer 699

Zn allows hexamer formation of insulin in storage granules allowing higher concentration within granules. Without Zn in granules, there would be lower insulin concentrations and therefore lower secretion levels

Answer 700

``` Pathology = study of morphological, biochemical and functional changes in cells, tissues and organs that underlie disease Etiology = initiating event or agent of a disease Pathogenesis = sequence of cellular, biochemical or molecular events that follow exposure of a cell/tissue/organ to an injury ```

Answer 701

1 Hypertrophy- cells grow in size 2 Hyperplasia- increase in cell number 3 Metaplasia- cells change from one cell type to another 4 Atrophy- cells decrease in size and/or number

Answer 702

Hyperplasia and hypertrophy often occur simultaneously Example: Uterus in response to pregnancy Hypertrophy occurs by itself whenever hyperplasia is not possible Ex: cardiac muscle in response to high blood pressure

Answer 703

Degradation of proteins/other components that are no longer required by Ubiquitin/proteasome system and autophagy

Answer 704

Metaplasia where non-keratinized squamous epithelium of the esophagus is converted to non ciliated mucin producing epithelium to cope with reflux of stomach acid into esophagus

Answer 705

Disordered cell growth that can occur in long-standing hyperplasia or Metaplasia. Often a proliferation of pre-cancerous cells and it is believed to be reversible if stress is removed

Answer 706

1 Cell physiology/type- certain cells are more sensitive to some stresses than others 2 Type of injurious stimulus 3 Strength/intensity of injurious stimulus 4 Duration of injurious stimulus

Answer 707

1 Cell swelling- occurs when ATP is low and cell can’t maintain ion/water homeostasis by active transport 2 Fatty change- lipid vacuoles appear in the cytoplasm if cells that depend on lipid metabolism as a result of toxic, metabolic or hypoxic injury

Answer 708

1 ATP depletion/decreased ATP synthesis 2 Mitochondrial damage 3 Loss of Ca2+ homeostasis 4 Oxidative stress (accumulation of free radicals) 5 Loss of selective membrane permeability 6 DNA and protein damage Often all of these occur simultaneously since any one could lead to others

Answer 709

Often caused by: Mitochondrial damage from hypoxic and toxic injuries Consequences: Reduced protein production Reduced membrane transport membrane maintainence impaired

Answer 710

Causes: Hypoxic/ischemic and toxic injuries Consequences: Lack of ATP production Formation of Reactive oxygen species Apoptosis of necrosis

Answer 711

Causes: Mitochondrial failure Plasma membrane damage Consequences: Increased mitochondrial permeability -> No ATP Activation of enzymes such as phosphlipases, porteases, endonucleases and ATPases that damage cell components and destroy ATP Induces apoptosis by activating caspas es

Answer 712

Causes: Accumulation of oxygen derived free radicals due to increased production or decreased scavenging Consequences: Membrane lipid peroxidation with propagating damage Oxidative modification of proteins which can disrupt structure, inactivate enzymes and cross link proteins DNA damage

Answer 713

Can occur at the plasma membrane, lysosomal membrane or mitochondrial membrane Causes: Reactive oxygen species Decreased phospholipid synthesis (ATP deficiency) Increased phospholipase activity Protease damage to cytoskeleton Consequences: Mitochondrial: decreased ATP production and caspase release Plasma membrane: lost osmotic balance, influx of Ca2+, loss of cytosol is contents (ATP) Lysosome: RNases, DNases, porteases phosphatases released into cytosol

Answer 714

1 Inability to reverse mitochondrial dysfunction | 2 Membrane damage to lysosome, mitochondria or plasma membrane

Answer 715

Both are forms of cell death Apoptosis is regulated by genes and proteins made by the cell, requires ATP, no inflammatory response, no loss of membrane integrity, often serves normal physiological functions Necrosis is unregulated and not programmed by cell, does not require ATP, triggers inflammation, results in loss of membrane permeability and is always the result of pathology

Answer 716

1 Coagulative: preserved organ/cell shape, no nucleus, typical of ischemic infarction everywhere except the brain acute inflammation 2 Liquefaction: tissue becomes liquid due to release of enzymes that lysis dead cells typical in brain , pancreas and abscess acute inflammation 3 Caseous: Cheese-like, Combination of liquefaction and coagulative necrosis occurring in TB chronic inflammation 4 Fat: necrotic adipose tissue becomes chalky white due to calcium deposition. Occurs in breast trauma and pancreatitis chronic inflammation 5 Fibrinoid: necrosis of blood vessel wall allowing fibrin to leak out of vessel in vasculitis and extreme high blood pressure

Answer 717

One of 4 basic tissue types in the body Generally lines body cavities, tubes and external surfaces Stained by cytoskeleton

Answer 718

1 Protection 2 Transportation 3 Glandular secretion 4 Sensation

Answer 719

Different parts of the cells have different shapes and functions 1 Apical domain- faces lumen 2 Lateral domain- faces other cells on the sides- closely attached by junctions 3 Basal domain- Sits atop the basement membrane

Answer 720

1 Based on number of layers - simple- 1 layer- all cells rest on basement membrane - Stratified- more than 1 layer 2 Based on cell shape - Squamous- flat, wider than it is tall - Cuboidal- equally wide and tall - columnar- taller than it is wide

Answer 721

1 Simple squamous 2 Stratified squamous 3 Simple cuboidal 4 Stratified cuboidal 5 Simple Columnar- nuclei all at same level 6 Pseudostratified-like simple columnar but nuclei are on different levels 7 Stratified columnar- looks like pseudo Stratified but not all cells are on the basement membrane 8 Transitional- stratified with dome shaped cells on the top layer

Answer 722

``` Functions Selectively permeable for rapid exchange Locations Respiratory spaces- alveoli Bowman’s capsule- kidney Endothelium- Blood vessels Mesothelium- body cavities ```

Answer 723

``` Functions Protection, absorption and secretion Locations Small ducts of exocrine glands Kidney tubules Thyroid follicles ```

Answer 724

``` Function Absorption and secretion Locations Stomach Small intestine and colon Gallbladder ```

Answer 725

``` Function Absorption, secretion and transport Locations Bronchial tree Vas deferens and epididymis ```

Answer 726

``` Function’ Protection Location Epidermis Oral cavity and esophagus Vagina ```

Answer 727

Cells are tightly connected to create a barrier Cells on top can be removed when damaged and replaced by cells from underneath May be keratinized (skin)

Answer 728

``` Functions Protection and conduit Locations Large ducts of exocrine glands (salivary, mammary, sweat) Anorectal junction ```

Answer 729

``` Functions Protection and conduit Location- very rare Largest exocrine ducts Anorectal junction ```

Answer 730

Function Distensible and protection Locations Lower urinary tract Distension allows changing shape to fit more or less liquid in bladder

Answer 731

Exocrine glands secrete products through their apical membrane into ducts which can add, remove or modify contents of secretions Endocrine glands on the other hand secrete their products, called hormones, through the basal surface through connective tissue and into the blood

Answer 732

1 Merocrine- exocytosis 2 Apocrine- budding of vesicles through membrane 3 Holocene- cell death with a ruptured membrane that releases secretion in vesicles

Answer 733

1 Serous- thin and watery containing enzymes and proteins | 2 Mucous- thick and slimy due to mainly glycoproteins

Answer 734

Goblet cells of the stomach which produce mucin a component of protective mucous of the GI and respiratory tract

Answer 735

The main way to recognize them is the large clear bubble of secretion at the top of them. You may also be able to notice that the cell looks like a goblet beneath these

Answer 736

``` Based on their ducts Simple- unbranched Compound- branched Based on their gland Tubular- tube shaped Alveolar/acinar- flask shaped Tubuloalveolar- sac like ``` Tubular secretary portions may be straight coiled or branched and alveolar secretary portions may be simple or branched

Answer 737

Simple tubular

Answer 738

Compound acinar glands | Pyramid shaped serous secreting cells

Answer 739

Simple coiled tubular

Answer 740

Large clear looking cytoplasm or clear “bubbles” within cytoplasm made of mucous Flattened nuclei

Answer 741

It is in contact with the outside environment so it has a lot of: ``` Enzymes Receptors Ion channels Carrier proteins And some special structures Microvilli Stereocilia Motile Cilia Non-motile cilia ```

Answer 742

Extensions of the membrane filled with actin bound to myosin and tropomyosin at the bottom that allows contractions to change the width that increase the surface area of the cells for greater absorption Found in Brush border of tubules Started border in the intestines

Answer 743

They are longer, immobile microvilli that serve as sensory mechanoreceptors. When they are moved by fluid around them, it initiates a signal transduction pathway Found in Hair cells of the inner ear Vas deferens and epididymus

Answer 744

Motile cilia have a 9+2 microtubule arrangement and are motile with dynein allowing ATP-dependent sliding movement by cross bridges between microtubules Primary cilia or non-motile cilia have a 9 + 0 arrangement. They are not motile instead they passively bend with fluid flow and open Ca2+ channels to begin a signal transduction pathway. They are made up of polycystin 1 and 2 genes.

Answer 745

Specialized motile cilia that are responsible for creating L/R asymmetry in the embryo

Answer 746

Autosomal dominant disorder of motile cilia resulting in loss of inner or outer dynein arms and therefore uncoordinated asynchronous beating of cilia. Symptoms: Poor mucociliary clearance leads to chronic bronchitis, sinusitis, otitis media, hearing loss, smell loss, respiratory infection and bronchiectasis Immotile sperm and non-functional cilia in uterine tubes leads to infertility Impaired nodal cilia leads to situs inversus- internal organs are a mirror image of where they would normally be

Answer 747

Autosomal dominant polycystic kidney disease Results from mutations to genes encoding polycystin proteins which make up primary cilia. Symptoms: Large cystic kidneys and cysts in other organs

Answer 748

1 Cadherin 2 Integrins 3 IGSF 4 Selectins 1 and 2: epithelial cell junctions 3 and 4: inflammation

Answer 749

They form Ca2+ dependent homodimers and associate with intracellular catenins which link them to the actin in the cytoskeleton They are important in cell-cell interactions such as tumor recognition E-cadherins are in epithelial cells

Answer 750

They form Ca2+ independent heterodimers of alpha and beta chains They are a key component in hemidesmosomes and are involved in cell-cell and cell-ECM binding. Involved in leukocyte binding and migration in tissues They also facilitate movement in the ECM

Answer 751

1 Zonula Occuldens (tight junctions) 2 Zonula adherens (intermediate junctions) 3 Mácula adherens (Desmosomes) 4 Gap Junctions They are listed in order from most apical to most basal The first 2 form belt-like rings around cells while macula adherens form spot welds and gap junctions are for communication

Answer 752

Also called tight junctions Made up of claudin and occludin proteins They create a barrier that prevents paracellular transport or movement of molecules between cells

Answer 753

Also called intermediate junctions Composed of actin/E-Cadherin -catenin complexes They anchor cells together

Answer 754

Also called desmosomes They are composed of specific cadherins called desmoglein and desmocolin which attach to desmoplakin and plakoglobin in the cytosol which bind keratin cytoplasmic filaments Their function is spot welds to further anchor cells together and they are found mostly in stratified squamous epithelium

Answer 755

Made up of the protein connexin which forms a hexamer called connexons. This structure forms a channel across the two membranes of adjacent cells to create a channel between them allowing for rapid communication

Answer 756

1 Focal adhesions | 2 Hemidesmosomes

Answer 757

Separates epithelium from underlying connective tissue Composed of two regions 1 Basal lamina- borders the basal membrane and is made up of laminins, type 4 collagen, glycoproteins and proteoglycans. 2 Reticular lamina- attaches to the underlying connective tissue, made up of reticular fibers

Answer 758

Focal adhesions anchor the basal membrane to the underlying basal lamina of the basement membrane. They are composed of integrins which are transmembrane proteins and attach to fibronectin, collagen and lamin in in the basal membrane as well as the actin cytoskeleton within the basal membrane cell’s cytoplasm. They are also involved in cell signaling and migration

Answer 759

They anchor the basal membrane to the basal lamina. They are composed mainly of BP230 and type 17 collagen which bind to laminin 5 and type 4 collagen in the basement membrane

Answer 760

Autoantibodies against desmogleins 1 and 3 interfering with the desmosomes in epithelial tissue. This causes flaccid blistering in response to shearing force where the top layers of epithelium will come right off while the basal layers remain connected to the basement membrane

Answer 761

Autoantibodies against BP230 or Type 17 collagen involved in hemidesmosomes. This interferes with basal domain attachments to the basement membrane leading to Tense blisters that do not rupture easily caused by basal domain pulling away from the basement membrane

Answer 762

Inherited defect in collagen 7 Collagen 7 makes up anchors between basement membrane and underlying connective tissue patients show extremely fragile skin that shears easily and falls off making sores and flaccid blisters due to loss of epidermal-dermal connection

Answer 763

Immunofluorescence which uses antibodies against the antibodies present in each of these autoimmune disorders to make the diagnosis

Answer 764

The function of a given tissue or organ is dependent on its structure

Answer 765

1 Acidic dyes carry a negative charge and bind to + charged components such as mitochondria, secretory granules, collagen, general cytoplasm, basement membrane. These things are called eosinophilia. Common acidic dyes are eosin, orange G and acid fuchsia. They appear red 2 Basic dyes carry + charge and bind to - charged components such as DNA and RNA (nucleus, RNA rich cytoplasm), carboxyl groups of proteins and sulfate in cartilage matrix. These things are called basophillic and they appear blue. common dyes are toluidine blue, Alicante blue and methylene blue

Answer 766

A common form of staining in histology that uses a basic dye hematoxylin and and acidic dye eosin. They appear purple in color

Answer 767

1 Epithelial tissue: covers surfaces and body cavities and lines organs. Defined by almost no ECM, junctions, polarity, supported by connective tissue, avascular and regenerative 2 Connective tissue: Protects and supports the body. Defined by cells + ECM, common origin from mesenchyme, and degrees of vascular it you from avascular to highly vascular 3 Muscle: Generates force to move body 4 Nervous tissue: communication and homeostasis

Answer 768

Cells + ECM ECM made up of 1 Protein fibers: collagen, reticular, elastic 2 Ground substance: proteoglycans, glycosaminoglycans, multiadhesive glycoproteins

Answer 769

``` 1 Loose 2 Reticular 3 Dense Regular 4 Dense Irregular 5 Adipose 6 Blood 7 Suporting : bone and cartilage ``` ``` 1-5 = connective tissue proper 6-7 = specialized connective tissue ```

Answer 770

O2 -> O2.- -> H2O2 -> OH.- -> H2O Step 1 = oxidases Step 2 = SOD supraoxide disputase Step 3 = Fenton Reaction O2.- supraoxide free radical OH.- Hydroxyl radical Radiation can also create free radicals by the following reaction: H2O -> O2.- + H.

Answer 771

1 Mitochondria- Complexes 1 and 3 of ETC create supraoxide from oxygen 2 Peroxisomes- involved in a number of oxidative processes including beta oxidation, amino acid catabolism, synthesis of bile acid, and synthesis of plasmalogens which can produce some ROS 3 NADPH oxidase in lysosomes of monocytes, macrophages and neutrophils- a five protein complex forms with 2 in the membrane and two cytosolic components which couples the oxidation of NADPH to the reduction of oxygen to supraoxide 4 Cytoplasm- Xanthine oxidase involved in amino acid catabolism generates supraoxide

Answer 772

``` 1 Inflammation 2 O2 therapy 3 Reperfusion following ischemic injury 4 Ionizing radiation 5 Chemicals 6 Aging ```

Answer 773

Too much or too little ROS Too much = direct damage and killing of cells Too little = Activate cell pathways, stimulate proliferation, damage lipids, proteins and DNA

Answer 774

``` Free radicals react with lipids to induce a chain reaction that turns lipids into low molecular weight aldehydes Consequences: 1 Structural changes in membranes: alters membrane bound proteins Increases ion permeability Changes membrane fluidity 2 Lipid peroxidation products: Form cross links with proteins and DNA Can be directly toxic Disrupt membrane signaling ```

Answer 775

They can create disulfide bonds, cause fragmentation or accumulation of proteins

Answer 776

Creates cross links and strand breaks Causes many base modifications leading to mutations Incorrect stimulation of DNA repair

Answer 777

Prooxidants are chemicals or molecules that cause the creation of more ROS Antioxidants prevent formation of ROS or contribute to scavenging of them

Answer 778

SOD- converts supraoxide to hydrogen peroxide Catalase- converts hydrogen peroxide to water Glutathionee peroxidase- converts hydrogen peroxide to water through glutathione reductase system

Answer 779

``` 1 Decreased functional demand 2 Decreased oxygen supply/blood supply 3 Starvation or malnutrition 4 Decreased trophic factors 5 Persistent cell injuries: chronic pressure, chronic inflammation, chronic disease, aging ```

Answer 780

In Bell’s palsy, facial nerve is cut leading to denervation of the muscles on one side of the face. These muscles atrophy because they no longer receive signals leading to non symmetrical facial muscles

Answer 781

1 Hydrocephalus- increased CSF puts pressure on brain leading to decreased size 2 Decubitis ulcers or bed sores result when increased pressure on a part of the body due to lack of movement causes atrophy of the skin in that area

Answer 782

In chronic gastritis, the chronic inflammation leads to atrophy of the epithelial layers lining the stomach

Answer 783

In cachexia, negative protein balance results from chronic diseases such as cancer leading to wasting away of muscle and other tissues independent of nutritional state

Answer 784

Hypoplasia is the incomplete development of a tissue Aplasia is the failure of a tissue or organ to develop at all Atrophy is decrease in cell number or size after development All result in smaller or nonexistent organs but atrophy occurs on an organ which developed fully after development is complete

Answer 785

1 Increased functional demand | 2 Increased trophic factors

Answer 786

1 Mechanical stretch 2 Growth factor binding 3 Growth factor agonists They induce signal transduction leading to altered gene expression including reinduction of fetal genes for myosin and atrial naturetic factor

Answer 787

1 Stores calcium ions 2 Involved in apoptosis 3 Produces reactive oxygen species

Answer 788

1 Abnormal metabolism- inadequate removal of a normal substance 2 Impaired protein folding 3 Inherited enzyme deficiencies- failure to catabolize a metabolite results in accumulation of that substrate 4 Deposition and accumulation of exogenous substances- Cell lacks enzymatic capability to degrade or remove a substance

Answer 789

Pathological accumulation of triglyceride vacuoles in hepatocytes. Occurs in diabetes, hypoxia, toxins, metabolic syndrome, and protein malnutrition Occurs due to abnormal metabolism that is impaired packaging and transport

Answer 790

Cholesterol often accumulates intracellularly in macrophages (foamy macrophages) in: 1 Xanthoma - nodules in tendons of the heel and knee 2 atherosclerosis

Answer 791

Lysosomal storage disorders Ex. Gaucher disease results from a deficiency in the enzyme glucocerebrosidase which breaks down glucocerebroside in the lysosome leading to accumulation of this substrate and related compounds (sphingolipids) in macrophages in the liver, lymph nodes, spleen and bone marrow

Answer 792

1 Excess reabsorption in kidney tubules in renal failure 2 Excess protein synthesis- Mott cells- excess synthesis of immunoglobulins 3 Gene mutations causing misfolding 4 Gene mutations causing defective transport 5 Toxin induced aggregation

Answer 793

1 Lipofuscin- golden brown pigment that accumulates normally in cardiomyocytes, skeletal muscle and neurons with aging- not pathological 2 Hemosiderin- yellow brown consisting of ferritin derived from hemoglobin accumulates due to too abnormally high iron, hemolytic anemia, yellow bruising or transfusions 3 Exogenous carbon (anthracosis) - appears dark black common in urban dwellers and does not seem to lead to cellular injury

Answer 794

Clear areas within cells

Answer 795

Two or more digits are fused together as a result of failure of those cells to undergo apoptosis during development.

Answer 796

1 Chromatin condensation and DNA fragmentation 2 Progressive cell shrinkage 3 Plasma membrane blebbing- large vesicles formed (apoptotic bodies) 4 Phagocytosis of apoptotic bodies

Answer 797

1 Autoimmune disorders- immune cells producing antibodies against self proteins undergo apoptosis -> if they don’t autoimmune disease results 2 Cancer- apoptosis is a normal mechanism to prevent cancer in cells with accumulation of mutations

Answer 798

``` 1 Intrinsic (mitochondrial-dependent): triggered by cellular stress 2 Extrinsic (death receptor-mediated): triggered by soluble factors 3 Granzyme B : triggered by lymphocyte recognition ```

Answer 799

A family of related proteins that have to do with apoptosis Some are anti-apoptotic (pro-survival) while others are pro-apoptotic Ratios of these two types of cells determine whether or not apoptosis occurs They are divided based on number of homologous domains to Bcl-2 (the first one discovered) 4 domains = anti-apoptotic 3 domains = pro-apoptotic (Bax family) 1 domain = pro-apoptotic (BH3 only family)

Answer 800

1 Pro-apoptotic BH3-only proteins are activated by cellular stress by increased expression, post-translational modification or release from sequestration 2 BH3-only proteins bind to pro-survival proteins like Bcl-2 and prevent them from inactivating Bax and Bak 3 Bax and Bak create channels in the mitochondrial membrane allowing cytochrome C to leak out 4 7 copies of apaf-1 protein combine with cytochrome c in the cytosol to form the apoptosis (wheel of death) 5 The apoptosome recruits procaspase 9 and causes it to become active 6 Caspase 9 activates effector/executioner caspases (3, 6, 7) which do damage to cellular structures resulting in apoptosis

Answer 801

Pro teases that are involved in apoptosis Initiators- 2, 8, 9 and 10 activate Effectors/executioners 3, 6, 7 which do damage to the cell resulting in apoptosis

Answer 802

They are proteins besides caspases that regulate apoptosis IAP = inhibitor of apoptosis - inhibits caspases Smac = promotes apoptosis by inactivating IAP’s when released from the mitochondria with cytochrome c AIF = apoptosis inducing factor- released from mitochondria with cytochrome c and travels to the nucleus where it induces DNA condensation and fragmentation

Answer 803

1 Binding of ligands to death receptors recruits and binds FADD Fas-associated death domain with their tails. 2 This creates the Death inducing signaling complex (DISC) which consists of receptors + FADD + pro caspases 8 and 10 (initators) 3 These caspases then activate effector/executioner caspases leading to apoptosis There is cross talk between this and intrinsic pathway in the form of Bid which is a member of the BH3-only family that activates Bax and Bak which create pores in the mitochondrial membrane

Answer 804

1 Granzyme B, a serine protease is released by cytotoxic T cells and natural killer cells along with perforin to cause apoptosis of virally infected cells 2 Perforin aids granzyme B in entering infected cells via endocytosis 3 Granzyme B activates the BH3-only protein bid by cleaving it as well as well as activates caspases 3 and 8 4 Caspases 3 and 8 are initiator caspases which then activate effector/executioner caspases which begin breaking down the cell components to begin apoptosis

Answer 805

P53 levels increase in response to cell damage, DNA damage or other stresses. It acts as a transcription factor in the nucleus increasing expression of BH3-only proteins. In the cytosol, it interacts with Bax and Bak to promote oligomerization which will cause mitochondrial membrane permeability P53 is mutated in about half of human cancers

Answer 806

Lysosomal enzyme degradation of cells and extra cellular matrix necrotic debris and bacterial products when present

Answer 807

Hydropic cells: appear lighter in color with water vacuoles and are swollen in size compared to normal cells Necrotic cells: are concentrated darker pink than normal cells and do not contain nuclei Exact appears of necrotic cells depends on the type of necrosis

Answer 808

1 Pyknosis- nucleus becomes smaller and more concentrated 2 Karyorrhexis- fragmentation of the nucleus 3 Karyolysis- Complete loss of nucleus

Answer 809

Proteins unfold and coagulate creating a thicker pink appearance and disorder within the cytoplasm

Answer 810

1 Scarring -> loss of organ function 2 Inflammation 3 Formation of ulcers and cavititary lesions 4 Calcification 5 Resolution 6 Autoimmune response and release of self-antigen

Answer 811

An autoimmune disease where antibodies exist against snRNP’s Symptoms include chronic inflammation, joint pain and swelling and butterfly rashes on the cheeks

Answer 812

Patients have a male karyotype and produce normal male hormones however they lack the receptors for these hormones which are transcription factors causing them to be unable to alter gene expression to promote masculinization

Answer 813

A cancer of white blood cells caused by a chromosome translocation

Answer 814

Triplet repeat expansion

Answer 815

Hemoglobin Bart’s is another name for alpha thalassemia with 4 mutated copies. It is neonatal lethal Cooley’s disease is major beta thalassemia which is not lethal but transfusion dependent

Answer 816

Achondroplasia is a form of dwarfism resulting in lack of growth in long bones caused by a mutation to the FGFR3 gene It is autosomal dominant

Answer 817

It increases expression of fetal hemoglobin

Answer 818

They are a family of detoxifying enzymes found in the smooth endoplasmic reticulum of liver cells embedded in the membrane

Answer 819

It is cAMP activated and ATP gated

Answer 820

In first order, the concentration decrease is proportional to both the rate constant (k) and the concentration whereas in Zero-order kinetics, the concentration decrease is equal to the rate constant (k) and is not influenced at all by the concentration

Answer 821

Thiopurine S-methyltransferase is an enzyme involved in phase 2 drug metabolism of thiopurines which can be used to treat some leukemia’s, inflammatory bowel disease, rheumatoid arthritis etc. Different alleles exist in the population with 1* leading to higher activity and 3*A leading to lower activity. This must be taken into account when administering thiopurines which can be dangerous in too high of concentrations

Answer 822

Both result in severe skin lesions and blisters after small amounts of force is applied. Epidermolysis bullosa simplex results from mutations to skin specific keratin while dystrophic epidermolysis bullosa is the result of mutations to collagen 7 which binds the basement membrane to the underlying dermis

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