Steve Harvey's Black and White Biochemistry Facts Flashcards
Chromatin Structure
Negatively charged DNA loops twice around positively charged histones
Histones rich in lysine and arginine
Nucleosome core= H2A, H2B, H3, H4 (two of each)
Histone H1 binds nucleosome and stabilizes nucleosomes
Heterochromatin
Condensed, transcriptionally inactive, sterically inaccessible
Heterochromatin= highly condensed
Euchromatin
less condensed, transcriptionally active, sterically accessible
Eu=true “truly transcribed”
DNA methylation
Template strand cytosine and adenine are methylated in DNA replication, which allows mismatch repair enzymes to distinguish between old and new strands in prokaryotes.
DNA methylation at CpG islands represses transcription
“CpG Methylation Makes DNA Mute”
Histone methylation
Usually reversibly represses DNA transcription. but can activate it in some cases
“methylation=muting”
Histone acetylation
Relaxes DNA coiling, allowing for transcription.
“Acetylation=Active”
Purines
PURe As Gold
Adenine and Guanine
Pyrimidine
CUT the PY
Cytosine, Thymine, Uracil
Adenosine Deaminase Deficiency
Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase prevents DNA synthesis and thus decrease lymphocyte count.
One of the major causes of autosomal recessive SCID
Lesch-Nyhan syndrome
HGPRT
Hyperuricemia - if guanine and hypoxanthine cannot be phosphorylated by HGPRT, they get turned into urea which causes gout (see yellow crystals in their shit).
pissed off, retardation, DysTonia
HGPRT .
(hypoxanthine to IMP and guanine to GMP)
X-linked recessive
Treatment: allopurinol or febuxostat
Patient can develop macrocytic anemia because folate and b12 can compensate to make up for lost purines
DNA replication: Helicase
Unwinds DNA template at replication fork
DNA polymerase III
prokaryotes only
Elongates leading strand by adding DNA to the 3’ end
proofreads with 3’ to 5’ exonuclease
DNA polymerase I
Prokaryotes only
Degrades RNA primer (via RNAse H), replaces it with DNA
Same as polymerase III but excises RNA primer with 5’ to 3’ exonuclease
DNA ligase
Catalyzes the formation of a phosphodiester bond within a strand of double-stranded DNA (joins okazaki fragments)
Telomerase
RNA-dependent DNA polymerase that adds DNA to 3’ ends of chromosomes to avoid loss of genetic material with every duplication
DNA mutations: Transition vs transversion
Transition- purine to purine or pyrimidine to pyrimidine
Transversion- purine to pyrimidine or vise versa
Silent mutation
nucleotide substitution but codes for same amino acid: often base change in 3rd position of codon (tRNA wobble)
Missense
Nucleotide substitution resulting in changed amino acid (called conservation if new amino acid is similar in chemical structure)
example: sickle cell disease
Nonsense
Nucleotide substitution resulting in early stop codon
“Stop the nonsense”
Frameshift
Deletion or insertion of a number of nucleotides not divisible by 3, resulting in misreading of all nucleotides downstream, usually resulting in a truncated, nonfunctional protein
Example: Duchenne muscular dystrophy
Nucleotide excision repair
specific endonucleases release the oligonucleotide containing damaged bases; DNA polymerase and ligase fill and reseal the gap, respectively. Repairs bulky helix-distorting lesions.
example: xeroderma pigmentosum, prevents repair of pyrimidine dimers because of ultraviolet light exposure
Mismatch repair
Newly synthesized strand is recognized, mismatched nucleotides are removed and the gap is filled and resealed
example: defective in hereditary nonpolyposis colorectal cancer and lynch syndrome (marshawn lynch is a mismatch or some shit)
Non homologous end joining
Brings together 2 ends of DNA fragments to repair double-stranded breaks, No requirement for homology
Mutated in ataxia telangiectasia
DNA/RNA protein synthesis direction
DNA and RNA are read in the 3’ to 5’ diraction
DNA and RNA are both synthesized 5’ to 3’
Drugs blocking DNA replication often have modified 3’ OH, preventing addition of the next nucleotide (chain termination)
mRNA start codons
AUG (or rarely GUG)
eukaryotes: codes for methionine
prokaryotes: codes for formylmethionine (f-met)
mRNA stop codons
UGA (U Go Away)
UAA (U Are Away)
UAG (U Are Gone)
RNA polymerases
Eukaryotes RNA polymerase 1: makes rRNA RNA polymerase 2: makes mRNA RNA polymerase 3: makes tRNA Prokaryotes 1 RNA polymerase makes all 3 kinds of DNA
RNA processing
initial transcript is called heterogenous nuclear RNA (hnRNA)
Processing: capping 5’ end (7-methylguanosine cap), Polyadenylation of 3’ end, splicing out of introns
Splicing of pre-mRNA
- Primary transcript combines with snRNPs and other proteins to forms spliceosome
- Lariat-shaped (looped) intermediate is generate
- Lariat is released to precisely remove intron and join 2 exons
antibodies to spliceosomal snRNPs (anti-smith antibodies) are highly specific for SLE
Anti-U1 RNP antibodies are highly associated with mixed connective tissue disease
tRNA: T-arm and D-arm
T-arm: contains the sequence for tRNA-ribosome binding
D-arm: contains dihydrouracil acid for recognition by the correct aminoacyl-tRNA synthetase
3’ CCA is the amino acid acceptor site
Golgi does what
modifies N-oligosaccharides on asparagine
adds o-oligosaccharides on serine and threonine
adds mannose-6-phosphate to proteins for trafficking to lysosomes
I-Cell disease (Inclusion cell disease)
inherited lysosomal storage disorder
defect in phosphotransferase leading to failure of the golgi to phosphrylate mannose residues on glycoproteins leading to proteins that are secreted extracellularly rather than delivered to the lysosome
coarse facial features, clouded cornea, restricted joint movement,
small, thin, lethargic, and high plasma levels of lysosomal enzymes (hydrolases and glycosylases).
Fatal in childhood
Signal Recognition Particle
Abundant cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER.
COPI
Golgi to golgi trafficking (retrograde)
Golgi to ER
COPII
Golgi to golgi trafficking (anterograde)
Er to Golgi
Clathrin
Trans-golgi to lysosome
Plasma membrane to endosomes (receptor mediated endocytosis like LDL receptor)
Proteasome
Barrel-shaped protein complex that degrades damaged or ubiquitin-tagged proteins. Defects in the ubiquitin-proteasome system are implicated in Parkinson disease.
Microtubule
Cylindrical structure composed of a helical array of polymerized heterodimers of α- and β-tubulin. Each dimer has 2 GTP bound.
Incorporated into flagella, cilia, mitotic spindles. Grows slowly, collapses quickly.
Also involved in slow axoplasmic transport in neurons.
Molecular motor proteins—transport cellular cargo toward opposite ends of microtubule tracks.
Dynein—retrograde to microtubule (+ to −).
Kinesin—anterograde to microtubule (− to +).
Drugs that act on microtubules
Microtubules Get Constructed Very Poorly
mebendazole, Griseofulvin, Colchicine, Vincristine/Vinblastine, Paclitaxel
Cilia structure
9+2 arrangement of microtubules
Axonemal dynein- ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets.
Kartagener syndrome
primary ciliary dyskinesia
immotile cilia due to a dynein arm defect
results in male and female infertility due to immotile sperm and dysfunctional fallopian tube cilia, respectively; increase risk of ectopic pregnancy. Can cause bronchiectasis, recurrent sinusitis, and situs inversus
What are the stains for intermediate fillaments:
TYPE Connective tissue Muscle Epithelial cells NeuroGlia Neurons
Connective tissue: Vimentin Desmin: Muscle Cytokeratin: Epithelial cells GFAP: Neuroglia Neurofilaments: neurons
Oubain does what
inhibits Na/K channel by binding to K+ site
Type 1 Collagen
Most common
Bone (made by osteoblasts)
Skin, Tendon, dentin, fascia, cornea, late wound repair
Type I: Bone (decrease production in osteogenesis imperfecta type I);
from fibroblasts and osteoblasts
Type II Collagen
Cartilage (including hyaline), vitreous body, nucleus pulposus;
Type II: cartwolage;
Made from chondrocytes
Type III Collagen
Skin, blood vessels, uterus, fetal tissue, granulation tissue
deficient in the uncommon vascular type of ehlers danlos syndrome;
made from smooth muscle cells and endothelial cells
Type IV Collagen
Basement membrane, basal lamina, lens
Defective in Alport syndrome, targeted by autoantibodies in Goodpasture syndrome;
made from endothelial and epithelial cells
Collagen synthesis Steps
- Synthesis (RER)
- Hydroxylation (RER)- requires Vit C
- Glycosylation (RER)- Problems forming triple helix leads to osteogenesis imperfecta
- Exocytosis
- proteolytic processing
- crosslinking- problem here leads to Ehlers-Danlos
Osteogenesis Imperfecta
Genetic disorder, most commonly autosomal dominant which leads to decreased production of other wise normal type 1 collagen (won’t hydroxylate on prolines and lysines)
Blue sclera due to the translucency of the connective tissue over the choroidal veins
PROGRESSIVE hearing loss (abnormal ossicles)
dental problems due to lack of dentin
Ehlers Danlos Syndrome
Faulty collagen syntheses causing hyperextensible skin, tendency to bleed and bruise and hypermobile joints
6+types, inheritance and severity vary, autosomal dominant or recessive
Associated with joint dislocation, berry and aortic aneurysms, organ rupture
Hypermobile type: most common (lysyl hydroxylase deficiency)
classical type: mutation in type V collagen (joint and skin problems)
Vascular type: deficient type III collagen
Menkes Disease
X linked recessive defect in ATP7A gene
Connective tissue disease caused by impaired copper absorption and transport.
leads to decreased activity of lysyl oxidase (copper is cofactor)
brittle kinky hair (called kinky hair disease), growth retardation, hypotonia
Elastin
rich in proline and glycine, nonhydroxylated forms
tropoelastin with fibrillin scaffolding
cross-linking takes place extracellularly and gives elastin its elastic properties
broken dwon by elastase, which is normally inhibited by alpha 1 antitrypsin
Wrinkles in aging are due to
decrease collagen and elastin production
Emphysema and elastin
Emphysema can be caused by alpha 1 antitrypsin deficiency resulting in excess elastase
Southern blot
Works with DNA
DNA is broken up, run on gel, denatured, radiolabeled, and then anneals to its complementary strand which is visualized
Northern blot
Works with RNA;
useful in studying mRNA levels;
Take mRNA and use P-cDNA probe to label it, can tell size and abundance
Western Blot
Sample proteins are separated on gel and labeled with antibodies;
Confirmatory test for HIV after a positive ELISA;
useful for identification and sizing of protein
Southwestern Blot
Identifies DNA-binding proteins like transcription factors
uses labeled oligonucleotide probes; uses P-cDNA probes like northern blots, but is looking at DNA protein interaction.
Indirect ELISA
Use a test antigen to see if a specifc antibody is present in the sample
a secondary antibody that glows is added to detect the first antibody
Direct ELISA
uses antibody to see if a specific antigen is present in the sample
a secondary antibody is coupled to a glowing enzyme that is added to detect the antigen
examples of codominance
Blood groups
Alpha 1 antitrypsin deficiency
Pleiotropy
one gene contributes to multiple phenotypic effects
PKU manifests with light skin, intellectual disability, and musty body odor
Dominant Negative Mutation
Exerts a dominant effect. A heterozygote prodeuces a nonfunctional altered protein that also prevents the normal gene product from functioning
Linkage disequilibrium
Tendency for certain alleles at 2 linked loci to occur together more often that expected by chance.
measured in a population, not in a family, varies by population
Mosaicism
Presence of genetically distinct cell lines in the same individual
Somatic mosaicism- mutation propagates through multiple tissues and organs
Gonadal mosaicism- mutation only in egg or sperm cells
McCune-Albright syndrome- genetics
Lethal disease if the mutation is somatic, survivable if the mutation is mosaic
Locus Heterogeneity
Mutations at different loci make the same phenotype
albinism
Allelic Heterogeneity
Different mutations in the same locus produce the same phenotype
Heteroplasmy
Presence of both normal and mutated mtDNA resulting in variable expression in mitochondrial inherited disease.
Uniparental disomy
Offspring receive 2 copies of a chromosome from 1 parent and 0 from the other
Heterodisomy indicates a meiosis 1 error
Isodisomy indicates a meiosis II error
Imprinting
at some loci, only one allele is active, the other is inactive. With one allele inactivated, deletion of the active allele leads to disease state
Prader-Willi Syndrome
Maternal imprinting: gene from mom is normally silent and paternal gene is deleted/mutated
Results in hyperphagia, obesity, intellectual disability, hypogonadism, and hypotonia
25% of cases due to paternal uniparental disomy (means two paternal genes received, both imprinted, no maternal genes)
Chromosome 15
Angelman Syndrome
Paternal imprinting: gene from dad is normally silent and maternal (chromosome 15)gene has micro deletion
results in inappropriate laughter, seizures, ataxia, severe intellectual disability
5% of cases due to paternal uniparental dismony
an angel of a man is silent
the kids are known as “happy puppets”
Autosomal dominant polycystic kidney disease
Autosomal dominant
bilateral massive enlargement of kidneys due to multiple large cysts
85% due to mutation in PKD1 (chromosome 16) (16 letters in “polycystic kidney”)
15% due to mutation in PKD2 (chromosome 4)
Familial adenomatous polyposis
Autosomal dominant
Colon becomes covered with adenomatous polyps after puberty. progresses to colon cancer if not removed
Mutation in chromosome 5 (apc gene) (polyp=5)
APC is tumor suppressor gene
fap with your hand (five fingers, chromosome 5)
Familial hypercholesterolemia
Autosomal dominant
elevated LDL due to defective or absent LDL receptor (no receptor mediated endocytosis)
leads to severe atherosclerotic disease early in life and tendon xanthomas (usually in achilles tendon)
Hereditary hemorrhagic telangiectasia
Autosomal dominant
inherited disorder of blood vessels
telangiectasia, recurrent epistaxis, skin discolorations, arteriovenous malformations, GI bleeding, hematuria
AKA Osler-Weber-Rendu syndrome
Hereditary Spherocytosis
Autosomal dominant
spheroid erythrocytes due to spectrin or ankyrin defect
hemolytic anemia, increase MCHC (mean cellular hemoglobin concentration)
treat with splenectomy
Huntingtons disease
Autosomal dominant
depression, progressive dementia, choreiform movements, caudate and putamen atrophy, and decrease levels of GABA and ACh in the brain
gene on chromosome 4, trinucleotide repeat disorder (CAG)
increase # of repeats leads to younger age of onset
Marfan syndrome
Autosomal dominant
Fibrillin-1 gene (FB1) mutation leading to connective tissue disorder affecting skeleton, heart, and eyes;
Tall, long extremities, pectus excavatum, hypermobile joints, long tapered fingers and toes, cystic medial necrosis of aorta leading to aortic incompetence and dissecting aortic aneurysms, floppy mitral valve, subluxation of the lenses
Multiple Endocrine Neoplasms (MEN)
Autosomal dominant
several distinct syndromes (1, 2A, 2B) characterized by familial tumors of endocrine glands, including pancreas, parathyroid, pituitary, thyroid, and adrenal medulla
MEN 2A and 2B are associated with ret gene - encodes receptor tyrosine kinase
RET MEN
Neurofibromatosis type 1
Neurocutaneous disorder characterized by cafe-au-lait spots and cutaneous neurofibromas
Autosomal dominant, 100% penetrance, variable expressivity, NF1 gene on chromosome 17
NF1 is a tumor suppressor gene. It normally encodes for a GAP (GTP-ase activating protein). GAPs suppresses RAS activity by making RAS hydrolyse GTP to GDP faster, reducing the amount of time RAS is in the “on” state.
Neurofibromatosis type 2
Autosomal dominant
Bilateral acoustic schwannomas, juvenile cataracts, meningiomas (meninges is dura, arachnoid, and pia mater), and ependymomas (tumor on the epithelial-like lining of the ventricular system)
NF2 gene on chromsome 22q (type 2=22)
Tuberous Sclerosis
Autosomal dominant
Neurocutaneous disorder with multi-organ involvement
numerous benign hamartomas
incomplete penetrance, variable expressivity
Von Hippel-Lindau Disease
Autosomal dominant
Disorder characterized by development of numerous tumors (cerebellar hemangioblastoma, renal cell adenoma, BILATERAL renal cell carcinoma, pheochromocytoma)
associated with deletion of VHL gene (tumor suppressor) on chromosome 3 (3p) (3 letters in VHL and RCC)
VHL gene normally inhibits hypoxia inducible factor 1 alpha (HIF1alpha normally is degraded when there is oxygen present)
VHL protein is a component of ubiquitin ligase
Cystic Fibrosis-genetics
Autosomal recessive
defect in CFTR gene on chromosome 7, deletion of Phe508 most common
Cystic Fibrosis-Pathophysiology
CFTR gene encodes an ATP-gated Cl- channel that secretes Cl into lungs and GI and resorbs Cl in sweat glands
Mutation causes misfolded protein, stays in RER, decrease Cl secretion and H2O, increased Na reabsoprtion, thick mucus
Cystic Fibrosis-diagnosis
increase Cl and Na concentration in sweat is diagnostic
can have contraction alkalosis, and hypokalemia
Cystic Fibrosis- Complications
Recurrent pulmonary infections (pseudomonas)
chronic bronchitis and bronchiectasis–> reticulonodular pattern on CXR, pancreatic insufficiency, malabsorption and steatorrhea, nasal polyps, meconium ileus in newborns, infertility in males (no vas deferens or sperm)
Fat soluble vitamin deficiencies (A, D, E, K)
Cystic Fibrosis-treatment
N-acetylcysteine to loosen mucus plugs (cleaves disulfide bonds within mucus glycoproteins), dornase alfa (DNAse) to clear leukocytic debris
also the antidote for acetaminophen overdose
Duchenne Muscular Dystrophy
X-lined frameshift mutation–> truncated dystrophin protein –> accelerated muscle breakdown
Weakness begins in pelvic girdle muscles and progresses superiorly
Pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle –> Gower maneuver
Onset before 5 years
Dilated cardiomyopathy is common cause of death
Duchenne= Deleted Dystrophin
Increased CPK, western blot and muscle biopsy diagnostic
Function of Dystrophin gene
DMD gene is longest coding region in human genome
increase chance of spontaneous mutation
dystrophin helps anchor muscle fibers, primarily in skeletal and cardiac muscle. connects intracellular actin to transmembrane proteins alpha and beta-dystroglycan which connect to the extracellular matrix
Becker Muscular Dystrophy
Usually X-linked point mutation in dystrophin gene without frameshift
less severe than Duchenne
onset in early adolescence or early adulthood
Deletions can cause both Becker and Duchenne
Myotonic Type 1 muscular dystrophy
CTG trinucleotide repeat expansion in the DMPK gene –> abnormal expression of myotonin protein kinase –> myotonia, muscle wasting, frontal balding, cataracts, testicular atrophy, arrhythmia
CTG repeat mutation
Fragile X syndrome
X-linked dominant defect affecting the FMR1 gene (Fragile x Mental Retardation), CGG trinucleotide repeat mutation
2nd most common intellectual disability
post-pubertal macroorchidism, long face with large jaw, large everted ears, autism, mitral valve prolapse, aortic root dilation
Xtra large testes, jaw, ears
Down syndrome
trisomy 21, nondisjunction of homologous chromosomes, huge increase if mom over 45
flat facies, intellectual disability, prominent epicanthal folds, single palmar crease, gap between 1st two toes, duodenal atresia, hirschsprung disease, congenital heart disease (atrial septal defect), Brushfield spots
Down Syndrome-Increase risk of
Increase risk of ALL, AML, alzheimer disease (>35), Atrial septal defects
Down Syndrome- findings in 1st trimester
increase nuchal translucency and hypoplastic nasal bone, serum PAPP-A is decreased, free beta-hCG is increased
Down Syndrome- Findings in 2nd trimester
quad screen shows: decrease alpha-fetoprotein, increase beta-hCG, decrease estriol, increased inhibin A
Edwards Syndrome
Trisomy 18
severe intellectual disability, rocker bottom feet, micrognathia, low set ears, clenched hands, prominent occiput, congenital heart and kidney disease.
Die in first year
Edwards findings before birth
PAPP-A and free beta-hCG are decreased in first trimester
Quad screen shows: decrease alpha-fetoprotein, decreased beta-hCG, decrease estriol, decreased or normal inhibin A
Patau Syndrome
Trisomy 13
intellectual disability, rocker bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart disease Death in first year
Patau syndrome findings before birth
decreased beta-hCG, decreased PAPP-A, and increase nuchal translucency
How does APC gene work
tumor suppressor gene
promote degradation of catenin protein (catenin promotes proliferation and works with cell adhesion) by phosphorylating catenin via the GSK3b
lose APC–> less catenin degradation –> cell proliferation
autosomal dominant mutation of APC gene results in FAP
APC tears APpart Catenin
FAPping is as easy as A.P.C. (A Penis Clench)
Mycophenolate mofetil
immunosuppressive
inhibit IMP dehydrogenase which turns IMP into GMP, stopping the synthesis of guanine nucleotide (purine)
Microvilli
Contain Microfilaments which have actin and myosin in them
Does not contain microtubules! (aka microvilli are not cilia)
Robertsonian translocation
Occurs when the long arms of 2 acrocentric chromosomes (chromosomes with centromeres near their ends) fuse at the centromere and the 2 short arms are lost. balanced translocations do not cause problems, unbalanced causes miscarriage, stillbirth, and chromosome imbalances (downs syndrome, patau syndrome)
usually happens in chromosomes 13, 14, 15, 21, 22
cri-du-chat syndrome
congenital microdeletion of the chromosome 5
microencephaly, moderate to severe intellectual disability, high pitched crying/mewing, epicanthal folds, cardiac abnormalities (CVD) are common
Williams syndrome
congenital microdeletion of long arm of chromosome 7 (deletes elastin gene)
distinctive elfin facies, intellectual disability, hypercalcemia (increase sensitivity to Vitamin D), well-developed verbal skills, extreme friendliness with strangers, cardiovascular problems.
Robin williams was extremely friendly, and the rope he used to hang himself was not very elastic (i’m so sorry)
22q11 deletion syndromes
CATCH-22
Variable presentation with Cleft palate, Abnormal facies, Thymic aplasia–> t cell deficiency, Cardiac defects, Hypocalcemia secondary to parathyroid aplasia
DiGeorge Syndrome
Thymic, parathyroid, and cardiac defects
aberrant development of 3rd and 4th pouches–> T-cell deficiency (no thymus) and hypocalcemia (no parathyroid)
Vitamins that are fat soluble
A, D, E, K
absorption dependent on gut and pancreas. Toxicity higher in fat than water soluble due to accumulation in fat
Steatorrhea syndromes (CF, sprue) cause deficiency
Water soluble Vitamins
B1, 2, 3, 5, 6, 7, 9, 12
C
all wash out easily from body except B12 and B9 which are stored in the liver
Vitamin A: function
also called retinol
involved in: visual pigments (retina), normal differentiation of epithelial cells into specialized cells, prevents squamous metaplasia, used to treat measles and AML
Found in liver and leafy veggies
Vitamin A: deficiency
night blindness (nyctalopia) dry, scaly skin (xerosis cutis) alopecia, corneal degeneration (keratomalacia), immune suppression
Vitamin A: excess
Arthralgias, skin changes (scaliness), alopecia, cerebral edema, psuedotumor cerebri, osteoporosis, hepatic abnormalities
**teartogenic (cleft palate, cardiac problems): this is why you need negative pregnancy tests before giving isotretinoin for acne
Vitamin B1: Function
Thiamine
in thiamine pyrophosphate (TPP)
Cofactor for: pyruvate dehydrogenase, alpha keoglutarate dehydrogenase, Transketolase, branched chain ketoacid dehydrogenase
Vitamin B1: deficiency
Thiamine impaired glucose breakdown Wernicke-Korsakoff Syndrome Seen in malnutrition and alcoholism diagnose by giving B1 and seeing if RBC transketolase activity goes up. Beri-Beri, dry and wet
Dry Beri-Beri
B1 thymine deficiency
Polyneuritis, symmetrical muscle wasting
Wet Beri-Beri
Hight output cardiac failure (dilated cardiomyopathy), edema
Vitamin B2: function
Riboflavin
Component of Flavins (FAD, FMN)
used as cofactors in redox reactions
e.g. succinate dehydrogenase reaction in TCA cycle
Vitamin B2: deficiency
Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth)
Corneal Vascularization
the Two C’s of B2
Vitamin B3: function
Niacin Constituents of NAD and NADP Derived from tryptophan synthesis requires vitamins B2 and B6 Used to treat dyslipidemia (lowers levels of VLDL and raises HDL) Nad derived from Niacin
too much causes flushing
Vitamin B3: Deficiency
Niacin
glossitis, pellagra
The three Ds - Dermatitis (dry skin) Diarrhea, Dementia
BEEFY red tounge with no chelosis
Deficiency from Hartnup disease (decrease tryptophan absorption), malignant carcinoid syndrome (increased tryptophan metabolism), isoniazid (decrease vitamin B6)
Vitamin B3: Excess
Facial flushing (induced by prostaglandins), hyperglycemia, hyperuricemia
Pellegra
Diarrhea, Dementia (also hallucinations), Dermatitis
Vitamin B3 deficiency
Vitamin B5
Pantothenate (5 is Pento)
Essential component of conenzyme A (CoA) and fatty acid synthase
Deficiency causes dermatitis, enteritis, alopecia, adrenal insufficiency
Vitamin B6: function
Pyridoxine
Converted to pyridoxal phosphate, a cofactor used in transamination (e.g. ALT, AST), glycogen phosphorylase, synthesis of cystathionine, heme, niacin, histamine, neurotransmitters (serotonin, epi, NE, dopamine, and GABA)
Vitamin B6: Deficiency
Pyridoxine
Convulsions, hyperirritability, peripheral neuropathy (can be from isoniazid and oral contraceptives), sideroblastic anemias due to impaired hemoglobin synthesis and iron excess
Vitamin B7: function
Biotin
Cofactor for 1 carbon transfers: pyruvate carboxylase, acetyl-Coa carboxylase, propionyl-CoA carboxylase
Vitamin B7: Deficiency
Relatively rare. Avidin in egg whites avidly binds biotin, some antibiotics
Dermatitis, alopecia, enteritis
Vitamin B9: function
Folic acid
converted to tetrahydrofolate (THF) a coenzyme for 1-carbon transfer/methylation reactions
important for the synthesis of nitrogenous bases in DNA and RNA
Folate found in foliage
Absorbed in the jejunum
Vitamin B9: deficiency
Macrocytic, megaloblastic anemia
Hypersegmented PMNs
glossitis, no neuro symptoms (separates it from B12)
Labs: increased homocysteine, normal methylmalonic acid. Most common vitamin deficiency in USA. Seen in alcoholics and pregnant women.
most common vitamin deficiency in US
Vitamin B12: Function
Cobalamin
Cofactor for homocysteine methyltransferase and methylmalonyl-CoA mutase
Found in animal products
stores in body last years, only decreased in vegans or absorption problem, or intrinsic factor deficiency, or no terminal ileum like in Crohns.
Vitamin B12: deficiency
Macrocytic megaloblastic anemia
hypersegmented PMNs
paresthesias, subacute combine degeneration (degeneration of dorsal columns and lateral corticospinal and spinocerebellar tracts) due to abnormal myelin
Associated with increased serum homocysteine and methylmalonic acid levels. prolonged deficiency causes irreversible nerve damage.
Vitamin C: Function
Ascorbic Acid
antioxidant
facilitates iron absorption (makes it Fe2)
needed for hydroxylation of proline and lysine in collagen synthesis
needed for dopamine Beta hydroxylase which converts dopamine to NE
Vitamin C: Deficiency
Scurvy: swillen gums, bruising, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages and corkscrew hair
weakened immune system
Vitamin C: Excess
Nausea, vomiting, diarrhea, fatigue, calcium oxalate nephrolithiasis, can increase iron toxicity in predisposed people (transfusion patients, hereditary hemochromatosis)
Vitamin D: Storage form and Active form
Storage: 25OH D3
Active: 1,25-(OH)2 D3 (calcitriol)
Vitamin D: function
increase intestinal absorption of Calcium and phosphate
Increase Bone mineralization
Vitamin D: deficiency
Rickets in kids, osteomalacia in adults, hypocalcemia tetany. Breastfed infants should get Vitamin D. Made worse by low light exposure, pigmented skin, prematurity
Vitamin D: Excess
Hypercalcemia, hypercalciuria, loss of appetite, stupor, Seen in sarcoidosis (increase activation of vitamin D by epitheliod macrophages
Vitamin E
Tocopherol/tocotrienol
Antioxidant (protects erythrocytes from free radicals)
Enhances warfarin effects
Deficiency: heeeemolytic aneeeemia, acanthocytosis, muscle weakness, posterior column and spinocerebellar tract demylenation
Vitamin K
Cofactor for gama-carboxylation of glutamic acid residues on various proteins required for blood clotting. Synthesized by intestinal flora.
Needed to activates factors II, VII, IX, X, and protein C and S
Deficiency: Neonatal hemorrhages with increased PT and increased aPTT but normal bleeding time (have sterile intestines, can’t make K), also after long course of antibiotics
Zinc
Essential for the activity of 100+ enzymes. important in the formation of zinc fingers (transcription factor motif)
Deficiency: delayed wound healing, hypogonadism, decreased adult hair (Axillary facial, pubic), dysgeusia, anosmia, acrodermatitis enteropathica
May predispose to alcoholic CIRRHOSIS
Ethanol Metabolism
Ehtanol coverted to acetaldehyde via the alcohol dehydrogenase (turns NAD into NADH), in cytosol
Acetaldehyde is converted to acetate via the acetaldehyde dehydrogenase (turns NAD into NADH), happens in mitochondria
Increases NADH/NAD ratio in liver
Increase in NADH/NAD ratio (as seen with ethanol) causes
lactic acidosis (pyruvate goes to lactate) Fasting hypoglycemia (Oxaloacetate goes to malate and stops gluconeogenesis) Hepatosteatosis (glyceraldehyde 3 phosphate goes into glycerol 3-phosphate and combines with FAs to make triglycerides) Shuts down TCA cycle and creates ketoacidosis and hepatosteatosis
Kwashiorkor
Protein malnutrition resulting in skin lesions, edema, liver malfunction (fatty due to decrease apolipoprotein). clinical picture is small child with swollen belly
Kwashiorkor=MEAL
Marasmus
Total calorie malnutrition resulting in tissue and muscle wasting, loss of subcutaneous fat, and variable edema
Marasmus results in Muscle wasting
Rate limiting step of Glycolysis
Phosphofructokinase-! (PFK-1)
increased by AMP and Fructose 2,6 bisphosphate
decreased by ATP and citrate
Rate limiting step of gluconeogenesis
Fructose-1,6-bisphosphatase
increased by ATP and acetyl-CoA
decreased by AMP and fructose 2,6, bisphosphate
TCA cycle rate limiting step
Isocitrate Dehydrogenase
increased by ADP
Decreased by ATP and NADH
Glycogenesis rate limiting step
Glycogen synthase
increased by glucose-6-phosphate, insulin, cortisol
decreased by EPI and glucagon
Glycogenolysis rate limiting step
Glycogen phosphorylase
increased by EPI, Glucagon, and AMP
Decreased by Glucose-6-phosphate, insuling, ATP
HMP shunt rate limiting step
Glucose-6-Phosphate Dehydrogenase (G6PD)
increased by NADP
decreased by NADPH
Pyrimidine synthesis rate limiting step
Carbamoyl Phosphate Synthetase II
Purine syntheses rate limiting step
Glutamine-phosphoribosylpyrophosphate amidotransferase (PRPP)
Decreased by AMP, Inonsine monophosphate (IMP), GMP
Urea cycle limiting step
Carbomoyl phosphate synthetase I
increased by N-acetylglutamate
Fatty acid synthesis rate limiting step
acetyl-CoA Carboxylase
increased by insulin, citrate
decreased by glucagon and palmitoyl-CoA
Fatty acid oxidation rate limiting step
Carnitine acyltransferase I
decreased by Malonyl-CoA
Ketogenesis rate limiting step
HMG-CoA synthase
Cholesterol rate limiting step
HMG-CoA reductase
increased by insulin and thyroxine
decreased by glucagon and cholesterol
Familial Hypocalciuria hypercalcemia
CaSR (calcium sensing receptor) has decreased sensitivity leading to decreased feedback to parathyroid hormone
Get increased PTH, increased serum Ca, and decreased Ca in 24hr urine
Gene on Chromosome 3q
Can fatty acids be gluconeogenic
It makes acetyl-coa so no it is not gluconeogenic.
Glycerol, the backbone of triglycerides, can be made into glycerol-3-phosphate so it is gluconeogenic.
Anaerobic glycolysis VS aerobic glycolysis: ATP production
Aerobic= 32ATP
anaerobic=2 atp
Net glycolysis in the cytoplasm
in: glucose+2 Pi+2 ADP+2 NAD
out: 2 pyruvate+2ATP+2NADH+2H+2H2O
What glycolysis steps require ATP as the input
glucokinase/hexokinase
Phosphofruckinase-1 (PFK-1)
What glycolysis steps create ATP
Phosphoglycerate kinase
Pyruvate Kinase
Electron transport chain and oxidative phosphorylation: complexes and what blocks them
Complex 1: NADH turned into NAD, blocked by Rotenone
Complex 2: turns FADH2 into FAD
Complex 3: blocked by antimycin
Complex 4: 1/2O2+2H–>H2O, blocked by Cyanide
Complex 5: ADP+Pi–>ATP, blocked by Oligomycin
Oligomycin
Blocks Complex 5 of ETC
Directly stops synthesis of ATP
Glucose-6-phosphate dehydrogenase deficiency
x-linked recessive disorder, most common human enzyme deficiency
more prevalent among blacks: Increases malaria resistance
Heinz bodies, oxidized Hemoglobin precipitates in RBCs
Bite cells, phagocytic removal of heinz bodies by splenic macrophages leaves cells bitten shaped
Essential Fructosuria
defect in fructokinase (makes fructose into fructose-1-p)
autosomal recessive
asymptomatic condition, fructose NOT trapped in cells
fructose high in urine
Fructose Intolerance
Defect in Aldolase B
Autosomal Recessive
Fructose-1-P builds up in cells, decreases Phosphate levels, inhibiting glycogenolysis and gluconeogenesis
Urine has glucose and reducing sugar in it
Symptoms: hypoglycemia, jaundice, cirrhosis, vomiting
Treatment: Avoid fructose and Sucrose (glucose+fructose)
FAB GUT
fructose intolerance is Aldolase B
galactose intolerance is urydyltransferse
Galactokinase Deficiency
deficiency of galactokinase
Autosomal Recessive
Galactitol builds up if galactose is in diet
galactose appears in blood and urine, infantile cataracts–> baby fails to track objects or develop a social smile
Classic galactosemia
No galactose-1-phosphate uridyltransferase
Autosomal recessive
damage is caused by accumulation of toxic stuff (galactitol in the lense of eye)
Symptoms: FTT, Jaundice, hepatomegaly, infantile cataracts, intellectual disability
Treat: exclude galactose and lactose (galactose+glucose) from diet
FAB GUT
fructose intolerance is Aldolase B
galactose intolerance is urydyltransferse
Sorbitol
Alcohol counterpart to glucose
traps glucose in cell
Glucose into Sorbitol via aldose reductase
Sorbitol into Fructose via sorbitol dehydrogenase
decreased Sorbitol dehydrogenase amounts
Build up of sorbitol in cells
causes osmotic damage
cataracts, retinopathy, peripheral neuropathy as seen with chronic hyperglycemia in diabetics
Lactase deficiency: Insufficient Lactase Enzyme
Dietary Lactose intolerance. Lactase functions on the brush border to digest lactose into glucose and galactose
Lactase Deficiency: Primary
Age-dependent decline after childhood (absence of lactase-persistent allele), common in people of asian, african and native american descent
Lactase Deficiency: Secondary
Loss of brush border due to gastroenteritis
Congenital lactase Deficiency
rare, due to defective gene
Stool demonstrates low pH and breath shows increased hydrogen content with lactose tolerance test. Intestinal biopsy shows normal mucosa in patients with hereditary lactose intolerance
Hyperammonemia
Can be aquaried (liver disease) or hereditary (urea cycle enzyme deficiency)
Results in excess in NH4 which depletes alpha-ketoglutarate, leading to inhibition of the TCA
Treatment: limit protein in diet, Benzoate or phenylbutyrate bind amino acids and let you excrete them.
Ammonia Intoxication
Tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision.
N-acetylglutamate
required cofactor for carbamoyl phosphate synthase I
Absence of N-acetylglutamate leads to hyperammonemia
Presentation is identical to carbamoyl phosphate synthetase I deficiency.
Increase ornithine with normal urea cycle ezymes suggests hereditary N-acetylglutamate deficiency
Ornithine transcarbamylase deficiency
most common urea cycle disorder
X-linked recessive (all other urea cycle enzyme deficiencies are autosomal recessive)
interferes with body’s ability to eliminate ammonia
often evident in first days of life
excess cabamoyl phosphate is converted to orotic acid
increased orotic acid in blood, decreased BUN, symptoms of hyperammonemia
Phenylketonuria
Autosomal recessive
Due to decreased phenylalanine hydroxylase or decreased tetrahydrobiopterin cofactor
Avoid asparatame (n-aspartyl-phenylalanine methyl ester)
Tyrosine becomes essential
Increased phenylalanine leads to excess phenylketones
Disorder of aromatic amino acid metabolism leads to musty body odor
Alkaptonuria
congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate
autosomal recessive: benign disease
Findings: dark connective tissue, brown pigmented selerae, urine turns black on prolonged exposure to air. May have debilitating arthralgias (homogentisic acid toxic to cartilage)
al capone is a tyrant and a homo homo but he is also a gent
Homocystinuria
Types (all autosomal recessive)
all forms reult in excess homocysteine
Findings: increased homocysteine in urine, intellectual disability, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), thrombosis, and atherosclerosis (MI and Strokes)
Cystinuria
hereditary defect of renal PCT and intestinal amino acid transporter for Cysteine, Ornithine, Lysine, and arginine (COLA)
Excess cystine in the urine can lead to precipitation of hexagonal yellow-brown cystine stones. Forms radio opaque crystals
nitroprusside cyanide test is diagnostic should be positive/purple
Autosomal recessive
treatment urinary alkalization and chelating agents, increased hydration
Von Gierke Disease (Type 1)
Glycogen storage disease
Glucose-6-phosphatASE deficiency (not to be confused with glucose-6 phosphate dehydrogenase deficiency)
Autosomal recessive
Severe fast hypoglycemia
Increased glycogen in liver, increase blood lactate, hepatomegaly
Treatment: frequent oral glucose, avoid fructose/galactose
your liver can break up glycogen, but cannot dephosphorylate glucose, so the glucose is trapped in the cells
Pompe Disease (Type II)
Glycogen storage disease Lysosomal alpha1,4-glucosidase deficient Autosomal recessive Cardiomyopathy and systemic fining leading to early death (Pompe trashes the Pump)
large tounge, hepatomegaly
Cori Disease (Type III)
Glycogen storage disease
Debraching enzyme (alpha-1,6-glucosidase) deficient
Autosomal recessive
milder form of type 1 with normal blood lactate levels
Gluconeogenesis still intact
McArdle Disease (Type V)
Glycogen storage disease
Skeletal muscle glycogen phosphorylase deficient (myophoshporylase)
Autosomal recessive
Increased glycogen in muscle, muscle cramps with strenuous excecise (patient will complain of sprinting, but walking is fine), myoglobinurea with exercise, arrhythmia, electrolyte abnormalities
Removes 1,4-glucosyl residues from the glycogen, freeing glucose-1-phosphate, which occurs in the cytosol
Type IV (Anderson) Glycogen storage disease
Glycogen storage disease no branching enzyme You die remember ABCD Anderson - Branching Cori - Debranching
Fabry Disease
Lysosomal Storage Disease Peripheral neuropathy of hands and feet (patients feel their extremities burning), angiokeratomas, cardiomyopathy deficient alpha-galactosidase A Ceramide trihexoside build up X linked recessive
Gaucher disease
Most common Lysosomal Storage Disease
Hepatosplenomegaly, pacytopenia, aseptic necrosis of femir, bone crises, gaucher cells (lipid laden macrophages that look like crushed tissue paper),
treatment is recombinant glucocerebrosidase
Deficient glucocerebrosidase
build up of glucocerebroside
Autosomal Recessive
gaucher - glucocerebrosidase
Krabbe - galactocerebrosidase
Niemann-Pick Disease
Lysosomal Storage Disease Sphingomyelinase deficient Sphingomyelin builds up Autosomal recessive Progressive neurodegeneration, cherry red spot on eyes, foam cells, hepatosplenomegaly (Tay-sachs has no hepatosplenomegaly)
No man picks (Niemann-Pick) his nose with his sphinger (sphingomyelinase)
ashkenazi jews
Tay-Sachs Disease
Lysosomal Storage Disease Progressive neurodegeneration, cherry red spots, lysosomes with onion skin, NO hepatosplenomegaly Hexosaminidase A deficient build up of GM2 ganglioside Autosomal recessive Frameshift mutation Tay-SaX lacks heXosaminidase.
ashkenazi jews
Krabbe Disease
Lysosomal Storage Disease
Peripheral neuropathy, developmental delay, optic atrophy globoid cells - remember the globe krabby patty thing? best burgers on the GLOBE and in the GALAXY (galacto…)
Deficient Glactocereborsidase
Galactocerebroside and psychosine builds up (its a psycho scene at the krusty krabbe)
Autosomal recessive
Metachromic Leukodystrophy
Lysosomal Storage Disease Central and peripheral demyelination with ataxia, demetia deficient arylsulfatase A Cerebroside sulfate builds up Autosomal recessive
the metachromic colored ARYans are you CEREbral Bros
Hurler Syndrome
Lysosomal Storage Disease
Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
deficient alpha-L-iduronidase
build up of heparan sulfate and dermatan sulfate
Autosomal recessive
“Hurler” is a funny way to say Hailey
Hailey is married to Ron swanson the ALPHA male because she said “I Do, Ron” (iduronase). And ron has bad eating habits so he needs a build up of heparin (buildup of heparan sulfate)
lmao
Hunter Syndrome
Lysosomal Storage Disease
mulder Hurler + aggressive behavior, no corneal clouding
Deficient Iduronate sulfatase
Build up of heparan sulfate, dermatan sulfate
X Linked recessive
Hunters need to be able to see (like hurler, but no corneal clouding) so they can hit their target (X-linked recessive)
Carnitine Deficiency
inability to transport LCFAs into the mitochondria, resulting in toxic accumulation.
Weakness, hypotonia, hypoketotic hypoglycemia
Acyl-CoA dehydrogenase deficiency
increased dicarboxylic acid, decrease glucose and ketonse
Acetyl-CoA is a + allosteric regulator of pyruvate carboxylase in glyconeogenesis
decrease acetyl-CoA leads to decrease fasting glucose
Autosomal recessive
Ketone Bodies
Fatty acids and amino acids in liver are converted to acetoacetate ad beta-hydroxybutyrate (to be used in muscle and brain)
Breath smells like acetone
urine test for ketones does not detect beta-hydroxybutyrate
Maple Syrup Urine Disease
Autosomal recessive
Blocked degradation of branched amino acids (isoleucine, leucine, valine)
decreased alpha-ketoacid dehydrogenase cause increased alpha-ketoacids in blood
causes severe CNS defect
Fed State (after a meal): where is energy coming from
Glycolysis and aerobic respiration
insulin stimulates storage of lipids, proteins, and glycogen
Fasting (between meals): where is energy coming from
Hepatic glycogenolysis
adipose release of FFA (minor)
Glucagon, adrenaline stimulate use of fuel reserves
Starvation days 1-3: where is energy coming from
Blood glucose levels are maintained: glycogenolysis, adipose release of FFA
Glycogen reserves depleted after 1 day, RBCs lack mitochondria and so cannot use ketones
Starvation days 3+:where is energy coming from
adipose stores, brain uses ketones mainly, after these are depleted vital protein degradation accelerates leading to organ failure and death
Amount of excess stores determines survival time
Apolipoprotein E
Mediates remnant uptake
works with all cholesterol molecules except LDL
Apolipoprotein A-I
Activates LCAT
works with chylomicrons and HDL
Apolipoprotein C-II
Lipoprotein Lipase cofactor (activates LPL)
works with Chylomicron, VLDL, HDL
Apolipoprotein B-48
Mediates chylomicron secretion
Works with chylomicrons, chylomicron reminants
Apolipoprotein B-100
Binds LDL receptor
Works with VLDL, IDL, LDL
Lipoprotein lipase
degradation of TG circulating in chylomicrons and VLDLs. found on vascular endothelial surface
Chylomicrons
Delivers dietary TGs to peripheral tissue
delivers cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their triacylglycerols
secreted by intestinal epithelial cells
VLDL
delivers hepatic TGs to peripheral tissue
secreted by liver
IDL
formed in the degradation of VLDL
delivers TGs and cholesterol to liver
LDL
delivers hepatic cholesterol to peripheral tissues
formed by hepatic lipase modifications of IDL in the peripheral tissue
taken up by target cells via receptor-mediated endocytosis
HDL
mediates reverse cholesterol transport from periphery to liver
acts as a repository for apoC and apoE which are needed for chylomicron and VLDL metabolism
secreted from both liver and intestine
alcohol increases synthesis
Type 1 hyperchylomicronemia
increased blood levels of chylomicrons, TG, cholesterol
Autosomal recessive
lipoprotein lipase deficiency or altered apoprotein C-II
causes pancreatitis, hepatosplenomegaly, eruptive pruritic xanthomas with no increase for atherosclerosis
Type IIa familial hypercholesterolemia
LDL cholesterol are increased in blood Autosomal dominant absent or defective LDL receptors Heterozygotes around 300mg/dl Homozygotes around 700mg/dl causes accelerated atherosclerosis MI before 20 can happen achilles xanthomas corneal arcus
Type IV- Hypertriglyceridemia
VLDL and TG increased in blood
Autosomal dominant
Hepatic overproduction of VLDL, causes pancreatitis
nonpolyposis colorectal cancer
what is going wrong with DNA
mismatch repair,
newly synthesized strand is recognized, mismatched nucleotides are removed, and the gap is filled in normal people
patient with coarse facial features, clouded corneas, restricted joint movement
I-cell disease
failure of golgi to phosphorylate mannose residues onto glycoproteins (which is normally used to take them to the lysosome)
6-month boy
small, vomits with bottled milk, jaundice, bilateral clouding of lenses, hepatomegaly, developmental delay
Classic galactosemia
autosomal recessive
galactose-1-phosphate uridyltransferase deficient
cannot convert galactose into glucose
Galactol does damage to eyes
galactokinase deficiency would be less severe with mostly corneal clouding
fatty liver in alcoholics is due to an increased ratio of what electron transporting molecule
increase in the NADH:NAD ratio when ethanol gets converted to acetaldehyde in the cytosol
Patient has normal female development but doesn’t have menarche
elevated testosterone and estrogen
androgen insensitivity
she’s a guy
there’s a whole house episode of it
what amino acids are required in the diet during periods of growth
Arg and His
infant with FTT, hypoglycemia, hepatomegaly
Von Gierke (type I) glycogen storage disease Cori disease (type III) glycogen storage disease
mneumonic for the glycogen storage diseases
Very Poor Carbohydrate Metabolism
Von Gierke - hypoglycemia, increased blood lactate, hepatomegaly
Pompe - heart problems, enlarged tongue, hepatomegaly
Cori - milder von girke, normal blood lactate
McArdle - painful cramps, myoglobinuria with sprinting, arrhythmia
I - Glucose-1-phosphatase
II - lysosomal alpha-1.4-glucosidase (acid maltase)
III - Debranching enzyme (alpha-1,6-glucosidase)
V - Skeletal muscle glycogen phosphorylase
IV is incompatible with life
intellectual disability, marfanoid habitus, lens subluxation
comes in with MI
what disease
Homocystinuria - excess homocysteine in urine, intellectual disability, osteoporosis, marfanoid habitus, kyphosis, lens subluxation, thrombosis, atherosclerosis
3 types, all autosomal recessive:
- cystathioneine synthase deficiency. homocystine -X-> cystathionine –> cysteine
(Tx: decrease methionine, increase cysteine, increase b12 and folate) - homocysteine methyltransferase deficiency. Homocysteine -X-> methionine (Tx is increase methionine)
- decreased affinity of cystathionine synthase for pyridoxal phosphate (give a shit ton of B6 and cystine)
female who comes in at around age 12 with enlarging clitoris
5alpha reductase deficiency - inability to convert
testosterone into DHT; male internal
genitalia, ambiguous external genitalia until
puberty (when increases in testosterone levels cause
masculinization)
increasing the michaelis-menten constant of an enzyme means what
something is competitively inhibiting it
niacin is derived from what amino acid
tryptophan
(can see pellagra in hartnup disease, which is characterized by a lack of tryptophan absorption)
(also can see pellagra in malignant carcinoid syndrome because of an increase in tryptophan metabolism)
loss of a tumor suppressor gene on chromosome 17
what disease
Li-Fraumeni syndrome - autosomal dominant disorder that causes cancers before the age of 45.
the gene is p53 and can lead to MANY different cancers
alcoholic with angiomas, confusion, slurring, and asterixis
what is going on
what do you give
hepatic encephalopathy due to buildup of ammonia.
can be treated with lactulose to generate NH4, low protein diet, and rifaximin (kills intestinal bacteria)
where is the first place in the body that urea is metabolized
converted to carbamoyl phosphate (by carbamoyl phosphatase with cofactor N-acetylglutamate) in the mitochondria!
Mnemonic for Autosomal Dominant diseases. Think Dominant
Hunting MEN FAP thier Tubes and Shperes in Hip Cafés and get Tele Chols from Li about Marfans.
Huntingtons Multiple Endocrine Neoplasia Tuberous Sclerosis Hereditary Sphereocytosis von Hippel-Lindau Cafe = Neurofibromatosis type 1 (NF2 is also dominant but doesn't have cafe au lait spots) familial hyperCHOLesterolemia Li-Fraumeni Marfans
lipoprotein lipase cofactor
ApoC-II
Mnemonic for X linked recessive.
a Fable about a Dutch Hunter with White eyes and Wiskers, wearing a Burton coat. He bites his hands and bleeds so he gets an OTC (over the counter) medication called G6
Fabry’s Disease
Deuchenne’s Muscular dystrophy (and Becker’s)
Ocular Albinism
Wiskott-Aldrich syndrome
Bruton’s Agammaglobulinemia
bite hands = Lesch Nyhan
Bleeding = Hemophilia
OTC = Ornitine Transcarbamylase deficiency
G6PD
patient comes in with pellagra like symptoms and neutral aminoaciduria
hartnup disease, inherited mutations in the B(not) transporter
failure to absorb tryptophan
(tryptophan is used to synthesize niacin)
lipoprotein lipase cofactor
ApoC-II
increased serum homocystine and methylmalonic acid levels
vit b12 deficiency
B12 is a cofactor for homocysteine methyltransferase
(transfers CH3 groups as methylcobalamin)
and methylmalonyl-CoA mutase.
Normal CD19+ B cell count,
decreased pro-B, decreased Ιg of all classes.
Absent/scanty lymph nodes and
tonsils.
X linked (bruton) agammaglobulinemia
Defect in BTK, a tyrosine
kinase gene p no B cell
maturation. X-linked recessive
(mostly in Boys).
x and y intercept of line-weaver burk plots
Y - intercept = 1/Vmax
(the y intercept goes up; Vmax goes down)
X- intercept = -1/Km
(slope goes up, Km goes down)
patient presents with cancer at a young age, and there are other people in her family with cancer diagnoses at young ages
cancers are breast, ovarian, and osteosarcoma, adrenocortical tumors
what syndrome?
what gene?
Li-Fraumeni syndrome (autosomal dominant)
mutation in p53
What is happening is someone on nitroprusside if they get confused and their lips turn pink
cyanide poisoning
inhibits cytochrome oxidase
you give a cephalosporin to an infant and see a bunch of bruising
what enzyme is affected
caboxylation of glutamic acid residues (gamma carboxylation of factors II, VII, IX, X) is decreased because they have a vit K deficiency (because their gut flora were killed
which of the sphingolipidoses causes demyelination with ataxia early in life
metachromic leukodystrophy
defect in arylsulfatase A
build up of cerebroside sulfate
small red papules on abdomen and scrotum, hyperkeratosis, paresthesias in the digits bilaterally and heat intolerance
Fabrys
X-linked recessive
build up of ceramide trihexoside
defect in alpha-galactosidase A
microcytic anemia with basophilic stippling, fatigue, myalgias, poor concentration, worked in a factory
what is going on
what metabolite is likely elevated in the urine
lead poisoning
delta-aminolevulinic acid
Familial hypocalciuric hypercalcemia
increased serum calcium, decreased calcium urine, increased PTH all due to a mutation in the calcium sensing receptor which is made from the calcium sensing receptor gene on chromosome 3q
Amyloidosis: where is the amyloid made that is getting deposited everywhere
The liver makes serum associated amyloid protein, which goes to the other organs and makes amyloid associated protein.
Needlestick injury: what chronic diseases are you likely to get
Hep C and Hep B > HIV (Unless you know the diseases of the patient, but if unknown it goes by epidemiology)
Pyruvate decarboxylase deficiency
Leads to build up of pyruvate, alanine, and lactate; also see increased ketoacids due to lack of energy; autosomal recessive; shows up early in life with seizures.
