MCM Final Flashcards
This protein sorting pathway is used for proteins destined for cytosol, mitochondria, nucleus, and peroxisomes
Cytoplasmic
This protein sorting pathway synthesizes proteins destined for the ER, lysosomes, plasma membranes, and for secretion
Secretory pathway
What is the protein sorting signal that, when present, destines proteins for the cytoplasm
> Trick question. No sorting signal for this destination.
What is the protein sorting signal that, when present, destines proteins for the mitochondria
A hydrophobic alpha helix
What is the protein sorting signal that, when present, destines proteins for the nucleus
Terminal Lys/Arg repeats
What is the protein sorting signal that, when present, destines proteins for the lysosome
M6P
What is the protein sorting signal that, when present, destines proteins for a secretory vesicle
Trp rich domain (absent of retention motifs too)
What is the protein sorting signal that, when present, destines proteins to stay in the ER
KDEL
What disease is caused by a defect in the enzyme required to tag proteins with an M6P signal?
I cell disease. Proteins (hydrolases to be specific) that should be sent to the lysosome are instead packaged for export from the cell and this causes release of harmful enzymes into the blood. Yikes.
Proteins sent to the mitochondria are recognized by what mitochondrial membrane transporters?
TIM and TOM
How are unfolded proteins protected in the mitochondria?
Binding to chaperones does the trick (HSP70 specifically)
How do nuclear proteins enter that membrane bound organelle?
Via specific nuclear pores
Large proteins destined for the nucleus require a nuclear localization signal which includes four basic residues. Which amino acids are present here?
Lys, Arg
Name the segment of a protein synthesized for secreting that binds ER targeting signal and then the ribosome during translation
Signal recognition particle
What is used to tether the ribosome/mRNA/peptide complex together (also causes temporary halt in translation)
Signal recognition particle (SRP)
Where do proteins undergo post-translational modifications?
ER or Golgi
When a protein contains an ER localization signal, that signal binds the SRP which will then bind what on the RER membrane?
SRP receptor protein
What confirmation will small proteins spontaneously assume
Native conformation
What could happen when large proteins fold without the help of chaperones
Aggregation or proteolysis
What is the term for a protein containing a barrel shaped compartment that admits unfolded proteins and catalyzes their folding? Does this require ATP?
Chaperonins, yes it is ATP dependent
What is the post translational process that converts inactive forms to active enzymes
Proteolytic cleavage
What are the 3 possible post translational protein modifications
Glycosylation, phosphorylation, disulfide bond formation
What post translational modification Occurs on extracellular proteins only
Glycosylation
What post translational modification can be either O linked or N linked
Glycosylation
What amino acids serve as binding sites for an O linked glycosylation of a protein post translationally
hydroxyl group of Ser or thr
What amino acids serve as binding sites for an N linked glycosylation of a protein post translationally
Amino group of Asn
What type of bond is formed with the addition of a glycosidic post translational modification
Ester
Disulfide bonds form between what functional group of cysteine residues?
Thiol (-SH)
Formation and reorganization of disulfide bonds occurs where
ER lumen
Beta cells of the pancreas produce what 20 residue peptide?
Preproinsulin
Preproinsulin has its signal peptide cut off in the ___ to form proinsulin
ER
How many intramolecular disulfide bridges form within insulin’s structure
2
Insulin moves past the golgi before accumulating in what for storing?
B granules
Proinsulin is cleaved twice to release a residue called what?
C peptide
Mature insulin is stored in granules as a hexamer bound to what cofactor
Zinc
Mature insulin is made of an A and B chained linked together by what?
2 disulfide bridges
Most abundant structural protein in vertebrates? (Hint it is heterotrimeric)
Collagen
What post translational modification activates procollagen
Hydroxylation of lysines at the 5’ end and prolines (and later it can be glycosylated)
What coenzyme is necessary for lysyl and prolyl hydrolases required to activate collagen?
Ascorbic acid (vitC)
Each gene occupies a specific place in the genome known as what
Locus (plural loci)
The function of what structure is to temporarily hold together 2 daughter DNA helices after replication and serves as attachment site for microtubules during division
Centromere
Repeated nucleotide sequences at the two ends of a chromosome essential for stability
Telomere
This word. Refers to an. Entire set of chromosomes from a. Single cell
Karyotpe
How many pairs of human chromosomes are autosomes
22 pairs (and we have 1 pair of sex chromosomes)
Term for 2 Identicle chromosomes join at a centromere
Chromatids
This substance is sometimes used to detect the amount of circulating insulin in assays (it can even distinguish between hypoglycemic disorders due to islet cell tumors and infusion of exogenous insulin)
C peptide
a mendelian term meaning that two genes are inherited separately from one another: the inheritance of one does not increase or decrease your chances of inheriting the other
law of independent assortment
what are the 3 genetic mechanisms of disease and examples of each
loss of function: dystrophin, duchenne MD
gain of function: oncogenes causing cancer
protein alteration: sickle cell anemia
what do you call the first person diagnosed in a pedigree? (usually denoted by an arrow)
proband
what term do you use to describe that males have only 1 X chromosome? (This is why X linked disorders show up far more frequently in men)
hemizygous
whats an example of an X linked dominant disease where phosphorus and calcium in blood is very low due to wacky reabsorption in kidneys
hypophosphatemia
the frequency at which a gene manifests itself
penetrance
range of phenotypes that vary between individuals with a specific genotype
variable expressivity
term describing a single disorder (or any trait) caused by mutation in genes at different chromosomal loci
locus heterogeneity
with mutations in collagen genes (could occur in chromosome 7 or 17) we obtain brittle bones and this condition is called what? what process is responsible for the fact that this disease can be caused by mutation at multiple different loci?
osteogenesis imperfecta, locus heterogeneity
When binding proteins and enzymes depart from a site of crossing over (during prophases I) the structure that is left where maternal and paternal chromosomes have exchanged parts is called what?
Chiasma
Homologs being to pair in prophase I of meiosis and form a 4 chromatid structure called what?
A bivalent
What event occurs at the chiasma?
Crossing over
Homologs are joined by what protein complex to hold them together during crossing over?
Synaptonemal complex
There is a small region of homology between the X and Y chromosome called what? This allows them to pair during meiosis
Pseudoautosomal region
What are events that increase genetic diversity in offspring
Random assortment, crossing over
A Y chromosome directs the genital ridge to develop into what adult structure
Testis
How/Why are all womens technically mosaics?
Half of the cells in a woman’s body inactivate the paternal X chromosome and the other half of the cells inactivate the maternal X.
What does it mean when a gene is “imprinted”?
Methylated (down regulation)
How many possible gametes can be produced from two parents thanks to random distribution of homologues
2^n = 2^23 = 8.4x10^6
When homologues fail to properly separate (common during egg development and increase with maternal age)
Nondisjunction
What meiotic deficiency is the leading cause of spontaneous abortion and mental retardation in humans?
Nondisjunction
Cells with an abnormal chromosome number are referred to as what? Cell with a normal number of chromosomes are called what?
Aneuploid, euploid
When in cell division is nondisjunction most likely to occur for an oocyte?
Meiosis I
Because male gametes undergo more mitotic cell divisions, they are more susceptible to what?
mutations
If the paternal chromosome 15 is deleted the child will develop what anomaly?
Prader willi syndrome
If the maternal chromosome 15 is deleted the child will develop what anomaly?
Angelman syndrome
What two. Equations are necessary to determine a value using hardy weinberg principle?
p2 + 2pq + q2 = 1
p + q = 1
What does consanguinity mean? Why is this a bad thing?
“Blood relation”
We use this to describe mating with a relative (incest) and it is more likely to produce offspring affected by rare autosomal recessive disorders
What is the difference between the terms plolygenic. And multifactorial?
Polygenic- trait determined by many genes
Multifactorial- environmental factors cause variation
In multifactorial diseases, what threshold must be crossed before the disease will be expressed?
Threshold of liability
Females have a higher risk threshold and therefore require more risk genes before developing what condition?
Pyloric stenosis (hypertrophy between stomach and duodenum)
…side note: because women need more genes before expressing the phenotype, affected women are more likely to pass the trait on to offspring than affected men!
Random evolutionary process that produces large changes in gene frequency especially in a small population
Genetic drift
When a population begins form a small group of individuals who mate within the population, we see a special case of genetic drift known as what?
Founder effect (albinism in Panama is an example)
The RNA sequence produced from transcription is identicle (except for C’s and U’s) to which strand of DNA
Coding strand
What is the purpose of a complementary hairpin near the 3’ end of a gene just before the polyU tail
It releases the newly synthesized strand from RNApol
What are the start and. Stop sequences of the genetic code??
Start- AUG
stop- UAA, UAG, UGA
Drug that binds 30S subunit of bacterial Ribosome to disrupt translation initiation
Streptomycin
Drug that binds 60S subunit of Ribosome to disrupt translation elongation
Shiga toxin
Drugs that binds 50S subunit of bacterial Ribosome to disrupt translocation of the ribosome
Clindamycin, erythromycin
Drug that binds 30S subunit of bacterial Ribosome to disrupt translation elongation
Tetracycline
What provides energy for assembly of the initiation complex to begin translation
GTP hydrolysis
What lab tests are used to diagnose Zika in the first 7 days of infection for individuals with symptoms
PCR of urine, serum, or saliva
What lab test would you use to diagnose Zika 2-12 days after onset of symptoms
Sandwich ELISA with anti-Zika IgM
These signaling molecules bind a promoter with a specific DNA binding domain plus a transactivating domain (binds RNA pol II) activating or inhibiting a gene
transcription factor
transcription factors can independently regulate the same gene in different tissues by binding to separate ___ for that gene?
enhancers
the capacity to respond to an inductive signal (such as a transcription factor signal during development)
competence
growth and differentiating factors are part of what family of signaling molecules essential to development? They are proteins (ligands) secreted by a cell and diffuse a short distance to interact with other cells.
paracrine signalling
60 amino acid helix turn helix DNA binding domain that is used to classify transcription factor family
homeodomain
the DNA sequence used to encode a homeodomain is a “homeobox” and homeobox containing genes are known as what?
HOX genes
genes that are related by duplication within a genome are called what? they evolve in function over time.
paralogous
this gene family plays an important role in caudo-cranial segmentation of the developing body
HOX genes
HOX genes are activated and expressed from 3’ to 5’. genes found at which end of the coding region are expressed earlier and more ANTERIORLY in the developing organism
3’
HOX genes are activated and expressed from 3’ to 5’. genes found at which end of the coding region are expressed later and more POSTERIORLY in the developing organism
5’
Which set of genes is complexly regulated and primarily is concerned with setting up segmental structures along the main body axis
HOX
what is the major regulator of HOX genes?
retinoid acid (vitA)
1) when HOX genes are mutated and upregulated (gain of function), what kind of malformation ensues?
2) when HOX genes are mutated and down regulated (loss of function), what kind of malformation ensues?
1) anterior to posterior transformation
2) posterior to anterior transformation
each gene in this gene family contains a 128 AA paired domain which binds DNA and plays critical role in formation of tissues and organs during embryo development
Pax genes
this pax gene disorder is characterized by complete or partial absence of the iris (PAX6 mutation)
aniridia
this pax gene is involved in making proteins that develop the eyes, CNS, and pancreas. when mutated, aniridia ensues
Pax6
this large family of homeodomain proteins bind both in the nucleus and cytoplasm. They are involved in formation of body segments and without them headless mammalian embryos result
Lim proteins
this phylogenetically conserved family of genes plays a role in patterning outgrowth of appendages in early embryogenesis and formation of jaws and inner ear
Dlx genes
this family of genes prenatally inhibits cell differentiation and postnatally helps to maintain proliferative capacity of tissues (involved in epithelial-mesenchymal interactions in the face and limbs)
Msx genes
this gene family causes short tails in heterozygous mice, is important ion mesodermal germ layer development, and differentiates forelimb from hindlimb
Tbx genes
this family of transcription factors have 2 alpha helices separated by a short amino acid loop with adjacent basic regions
helix loop helix TF’s
this configuration is common in TF’s that regulate myogenesis
helix loop helix & zinc finger proteins
helix loop helix and zinc finger transcription factors are common in regulating what part of development
myogenesis
TF family that regulates expression of genes involved in cell growth, proliferation, differentiation, longevity (and they contain a winged helix)
Fox gene family
the first gene associated with disorders of speech and language development (which are highly heritable)
FoxP2
this configuration of transcription factors include cys and his units bound by a cofactor which causes puckering in the polypeptide chain which can be inserted into specific regions of DNA helix
zinc finger proteins
this configuration of transcription factor is implicated in bone, cartilage, and tooth development
zinc finger
a deficiency in this metal ion can result in skeletal growth retardation (risk for osteoporosis)
zinc
this gene family binds the minor groove in DNA using zinc finger proteins. they are part of HMG-box superfamily and mutations lead to abnormal development of tissues such as sex determining genes
Sox (SoxA=SRY sex determining region of Y)
this disorder is caused by sox9 mutations effecting skeletal, reproductive, respiratory, and face development resulting in short legs, dislocated hips, ambiguous genet alit, softened respiratory cartilage, ect
campomelic dysplasia
campomelic dysplasia is caused by mutations in which gene
sox9
this zinc finger protein affects an isolated gene with important role in kidney and gonadal development
WT1 (wilms’ tumor supressor gene)
what are the zinc finger TF’s that we need to know?
WT1 (wilms tumor- kidney) and sox (bone, repro, respiratory issues)
this superfamily of signaling molecules plays a variety of roles in embryogeneiss and postnatal life (formation, structure, modification)
TGF-beta (transforming growth factor)
noggin, chordin, WNT3a, and FGF all “inhibit the inhibitor” of neural development. what is this inhibitor which they block so that neural development can occur?
BMP4 (important in skeletal development)
if bmp4 is present, then ectoderm becomes ___ whereas if it is blocked, then ectoderm becomes ____
epidermis, neural plate
angiogenesis, wound healing, embryo development of limb and brain, and various endocrine signaling pathways are all influenced by this family of proteins
fibroblast growth factors
this protein family uses ligand signaling by binding to PTCH receptors which signal transmembrane SMO protein
hedgehog
what are the 3 hedgehog proteins?
sonic, desert, indian
vertebrate organogenesis, facial and limb patterning, brain organization is all influenced by what signaling factor
SHH
this growth factor is essential in stem cell division in adults and has been implicated in cancer development
SHH
this signaling factor is involved in chondrocyte differentiation, proliferation, maturation especially during endochondral ossification
IHH (indian hedgehog)
defects in this signaling factor causes partial gonadal dysgenesis (PGD) and polyneuropathy
DHH (desert hedgehog)
this signaling factor is important in gastrulation and organogenesis and binds frizzled and LRP receptors, uses a signal transducer to beta catenin which enters nucleus to activate target genes
wnt
these genes regulate cell growth and differentiation and can lead to cancer when activated (usually code for mitogenic signals)
proto-oncogenes
these genes normally function to limit frequency of cell division and when they lose function, cancer may develop
tumor supressor genes
which tumor suppressor gene, when it loses function, leads to basal cell carcinoma
PTCH
RAS, HER2, EFT receptor, MYC, and ABL are all examples of what kind of cancer causing gene
proto-oncogene
p53, RB, APC, DCC, BRCA, and NF-1 are all examples of what kind of cancer causing gene
tumor supressor
activation of p53 leads to p21 activation which is a protein that binds cyclin-CDK complexes for G1/S transition. This process keeps ___ hypophosphorylated and active, and consequently sequesters ___
Rb, E2F
during early development, this signal molecule is generated in a region of the embryo to determine anterior/ posterior axis development by acting through box genes. what is the signaling molecule?
retinoid acid (vitA)
cultured embryonic stem cells can be coaxed into becoming neurons if you add what signaling molecule?
retinoic acid
the heavy and light chains of an antibody together form what portion of the structure
Fab portion
the Fc portion of an antibody contains components of which chains?
heavy chains only
the portion of an antigen to which an antibody attaches
epitope
in a method known as indirect detection, two ___ are used (the second one is fluorescently labeled) to amplify a detectable signal
antibodies
enzyme amplification assay frequently used in medicine the amount of antibody present in solution as it binds an antigen coated well (test for HIV Ab’s)
indirect ELISA
enzyme amplification assay where production of color indicates the quantity of antigen between one bound and one unbound monoclonal antibody which emit color when substrate is added (test for hCG: pregnancy)
sandwich ELISA
what lab method is used to detect cardiac troponin T before and after an MI
ELISA
what lab method uses DNA transcription as a diagnostic tool to find short tandem repeats (STRs) or viral particles
PCR
what are examples of conditions diagnosed using PCR?
chlamydia, CMV, Hep C, tuberculosis, gonorrhea
MSUD, ornithine transcarbamoylase deficiency, PKU, CF, Duchenne MD, Rb, familial hypercholesterolemia, sickle cell anemia, G6P dehydrogenase deficiency, tay sachs, hemophelia, lesh nyhan syndrome
…so when in doubt, its probably diagnosed using PCR :)
what are examples of conditions diagnosed using qPCR?
strep, HIV
name the technique where reverse transcriptase is used to make DNA from RNA sample and we add fluoresent marker linked to a probe to find a complementary sequence. a scanner measures expression. What are examples for use of this method?
microarray
chemo-resistant tumors
which viruses are known to be oncogenic
EBV, Hep B, HPV, HTLV-1, KSHV (kaposi sarcoma herpes virus)
Zika has an advantage in humans because of what disguise?
It acquires an envelope from our cells
What is the most devastating time to acquire zika in a pregnant woman? Why?
First trimester
Organogenesis (infects neural cells)
What property of signalling molecule allows it to diffuse across the cytoplasmic membrane and bind intracellular receptors?
Small hydrophobic (steroid hormones for example)
Most signalling molecules require cell surface receptors because they have what property?
Hydrophillic (such as growth factors)
Retinoic acid is a vitamin A derivative that acts through which set of developmental genes? These genes control positioning along which body axis?
Hox genes, these control anterior/posterior patterning
what method of cell signaling elicits a fast response
change in function of enzymes
what method of cell signaling elicits a slow response
change in expression of genes
Long distance signaling in the bloodstream of freely diffusible signals
Endocrine
Signaling acting locally on cells nearby using short lived signals such as neurotransmitters
Paracrine
Cells respond to signals released by themselves such as growth factor
Autocrine
Signalling involving direct contact with receptor such as with antigen presentation in immune cells
Juxtacrine
the same ligand can elicit different responses when introduced to different tissues for example: acetylcholine causes heart muscle cells to do what? skeletal muscle? salivary gland?
relax, contract, salivate
where would you find a receptor for a small hydrophobic ligand? what about a receptor for hydrophilic molecules?
intracellular, cell surface
what are the hydrophobic ligands?
cortisol, estradiol, thyroxine, testosterone, vitD3, retinoic acid
what kind of receptor is most commonly the target of drugs
GPCR
g proteins are regulated in part by two enzymes that help facilitate the production and hydrolysis of GTP. Which enzyme activates a GPCR and which inhibits?
activates- GEF- exchanges GTP for GDP and keeps GPCR in active state (GTP bound)
inhibit- GAP- hydrolyzes the GTP bound to GPCR so that it “turns off” (GDP bound)
which subunit of a gpcr is catalytically acitve
alpha
