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119 Cards in this Set
- Front
- Back
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Adenosine deaminase deficiency
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excess ATP and dATP lead to feedback inhibition of ribonucleotide reductase, preventing DNA synthesis and decreasing lymphocytes
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Lesch-Nyhan
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HGPRT deficiency, so hypoxanthine can't go to IMP and guanine can't go to GMP
results in excess uric acid production retardation, self-mutilation, gout, choreoathetosis |
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Orotic aciduria v. OTC deficiency
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megaloblastic anemia in both that does not improve with B12 or folate
in OTC deficiency only, hyperammonemia |
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promoter sequences
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CAAT
TATA |
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enhancer
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DNA that alters gene expression by binding transcription factors
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poly-A on which end?
what is signal? 5' cap? |
3'
AAUAAA 7-methylguanosine |
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SLE makes antibodies to what mRNA modifiers?
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spliceosomal snRNPs
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Beta-thal is example of what form of exon rearrangement?
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alternative splicing
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Hydroxyurea
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inhibits ribonucleotide reductase
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6-MP
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blocks de novo purine synthesis
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5-FU
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inhibits thymidylate synthase (decreased dTMP)
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MTX
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inhibits dihydrofolate reductase (decreased dTMP)
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trimethoprim
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inhibits BACTERIAL dihydrofolate reductase (decreased dTMP)
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AAs necessary for purine synthesis?
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glycine
aspartate glutamine |
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what histone is not in octamer?
what AAs dominate in octamer? |
H1
lysine, arginine (+ charged) |
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MOA of tetracyclines?
micharged tRNA? |
bind 30S subunit, preventing attachment of aminoacyl-tRNA
reads usual codon but inserts wrong amino acid |
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what is "tag" for defective proteins to undergo proteosomal degradation?
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ubiquitin
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protein synthesis: "going APE"
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A site - incoming Aminoacyl-tRNA
P site - accomodates growing Peptide E site - holds Empty tRNA as it exits |
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how many nucleotides is tRNA?
what sequence at 3' end? what binds here? |
75-90 (tiny)
CCA, amino acid |
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how are zymogens activated?
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removal of N or C-terminal propeptides
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in what cell cycle stage are permanent cells?
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G0
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what cells never go to G0?
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labile cells e.g. bone marrow, gut, skin, hair
divide rapidly with a short G1 |
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what is order of the cell cycle?
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mitosis
interphase (G1, S, G2) stable/quiescent cells may enter G1 from G0 |
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what proteins prevent cells from going to S phase?
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Rb, p53
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rough ER v. smooth ER
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rough ER: secretory proteins, oligosaccharide addition to many proteins
smooth ER: steroid synthesis, drug and poison detox |
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I cell disease
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inherited lysosomal storage disorder, failure of addition of mannose-6-phosphate to lysosome proteins
coarse facial features, clouded corneas, restricted joint mvmt, high plasma lysosomal enzymes (fatal in childhood) |
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COPI v. COPII
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COPI: retrograde (Golgi to ER)
COPII: anterograde (RER to cis-Golgi) |
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Chediak-Higashi
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microtubule polymerization defect resulting in decreased phagocytosis
recurrent pyogenic infections, partial albinism, peripheral neuropathy |
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3 drugs that interfere with microtubules
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vincristine (cancer)
paclitaxel (BRCA) colchicine (gout) |
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For each stain, give cell type:
1. vimentin 2. desmin 3. cytokeratin 4. GFAP 5. neurofilaments |
1. connective tissue
2. muscle 3. epithelial cells 4. neuroglia 5. neurons |
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Na-K-ATPase
How does ouabain inhibit? How do cardiac glycosides work? |
3 Na+ go out and 2 K+ come in
binding K+ site inhibition of Na-K-ATPase, which inhibits Na/Ca2+ exchange, increasing intracellular Ca2+ and increasing cardiac contractility |
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Collagen:
Be (So Totally) Cool, Read Books |
I - bone, skin, tendon, late wound repair
II - cartilage, vitreous, nucleus pulposus III - reticulin = skin, blood vessels, uterus, fetal and granulation IV - basement membrane |
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6 steps of collagen
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1. synthesis (RER)
2. hydroxylation (ER; Vit C) 3. glycosylation (ER; triple helix formed) 4. exocytosis into EC space 5. cleavage of terminal regions (now insoluble tropocollagen) 6. cross-linking (lysine-hydroxylysine; now FIBRIL) |
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Ehlers-Danlos
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type III collagen defect, usually
hyperextensible skin, joints easy bruising, bleeding |
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OI - inheritance?
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AD
1:10,000 incidence |
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Alport's syndrome
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variety of gene defects, abnormal type IV collagen (kidneys, ears, eyes)
most commonly X-linked recessive |
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Marfan's syndrome
other conditions associated with Marfanoid habitus? |
defect in fibrillin (scaffolding for tropoelastin)
MEN2B, homocystinuria |
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alpha1-antitrypsin deficiency
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excess elastase, results in panacinar emphysema
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locus heterogeneity
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mutations at different loci can produce the same phenotype
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heteroplasmy
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presence of both normal and mutated mtDNA
variable expression of mitochondrial inherited disease |
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allele prevalence
disease prevalence |
p + q = 1
p^2 + 2pq + q^2 = 1 |
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Leber hereditary optic neuropathy
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mtDNA inheritance (only through mother)
degeneration of retinal ganglion cells and axons, leads to acute loss of central vision |
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Give the location of the genetic error:
1. ADPKD (polycystic kidney) 2. FAP 3. Huntington 4. NF type I 5. NF type II 6. von Hippel-Lindau 7. Cystic fibrosis |
1. 16 (16 letters in "polycystic kidney")
2. 5 (5 letters in "polyp") 3. 4 ("Hunting 4 food") 4. 17 (17 letters in "von Recklinghausen") 5. 22 ("2 = 22") 6. 3 (3 words: "von Hippel-Lindau") 7. 7 (CFTR -508) |
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Name the X-linked recessive disorders
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Bruton's, Wiskott-Aldrich, Fabry's, G6PD, Ocular albinism, Lesch-Nyhan, Duchenne's (and Becker), Hunter's Syndrome, Hemophilia A and B
"Be Wise, Fool's GOLD Heeds Silly Hope" |
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defect in Duchenne's v. Becker's
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Duchennes: frameshift leads to gene deletion
Becker: gene mutation both are XLR inheritance |
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repeat in fragile X?
phenotype? |
CGG
X-tra large testes, jaw, ears |
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Give the repeat
1. Huntington's 2. Myotonic dystrophy 3. Fragile X 4. Friedreich's ataxia |
1. CAG (Caudate loses Ach and GABA)
2. CTG (myoTonic) 3. CGG (fraGile, fraGile) 4. GAA (ataxia, ataxia) |
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Down syndrome associated diseases
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heart disease (septum primum: ASD)
ALL Alzheimer's at 35 |
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Edwards' syndrome
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trisomy 18 (most common following Down's)
severe MR micrognathia clenched hands rocker-bottom feet |
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Patau's syndrome
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trisomy 13
cleft Palate holoProsencephly Polydactyly congenital heart (Pump) disease |
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Cri-du-chat
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microdeletion of 5p
microcephaly, moderate MR high pitched cry/mewing cardiac abnormalities |
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22q11 deletion syndromes
(DiGeorge and velocardiofacial) |
"CATCH-22"
Cleft palate Abnormal facies Thymic aplasia Cardiac defects Hypocalcemia (secondary to parathyroid aplasia) due to 22q11 deletion |
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vitamin A excess
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arthralgias, alopecia, skin changes, TERATOS
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B1 (thiamine) deficiency
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Wernicke-Korsakoff syndrome
beriberi (ber1ber1) |
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B2 (riboflavin) deficiency
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cheilosis, corneal vascularization (the 2 C's)
riboFlavin for FAD and FMN (B2 = 2 ATP) |
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B3 (niacin) deficiency
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glossitis, pellagra (also from Hartnup, malignant carcinoid, INH)
NAD derived from niacin (B3 = 3 ATP) |
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mechanism of pellagra
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decreased tryptophan (decreased absorption, increased metabolism)
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3 D's of pellagra
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diarrhea, dementia, dermatitis
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B5 name, function
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pantothenate = Coenzyme A
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SAM function
ingredients for SAM synthesis? |
"SAM the methyl donor man"
ATP + methionine |
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what drugs can cause folate deficiency?
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phenytoin, sulfonamides, MTX
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when is SAM necessary?
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conversion of Norepi to Epi
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vitamin E dysfunction
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increased Erythrocyte membrane damage from free radicals
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vitamin K necessary for which clotting factors?
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II, VII, IX, X, proteins C and S
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limiting reagent in ethanol metabolism?
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NAD+
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Kwashiorkor v. marasmus
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Kwashiorkor from protein-deficient MEAL (Malnutrition, Edema, Anemia, Liver is fatty)
Marasmus = Muscle wasting |
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metabolic processes in mitochondria
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Beta-oxidation, acetyl CoA production, TCA cycle, oxidative phosphorylation
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metabolic processes in cytoplasm
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glycolysis, fatty acid synthesis, HMP shunt, protein synthesis (RER), sterior synthesis (SER)
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metabolic processes in BOTH cytoplasm and mitochondria
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(HUGs take two)
Heme synthesis Urea cycle Gluconeogenesis |
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phosphorylase v. phosphatase
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phosphorylase ADDS phosphate
phosphatase TAKES phosphate (phosphaTAKE) |
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dehydrogenase v. carboxylase
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dehydrogenase oxidizes (takes electrons)
carboxylase adds 1 carbon with help of biotin |
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glucokinase function
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phosphorylates excess glucose (after a meal) to sequester it in liver (first step of glycogen synthesis)
INDUCED BY INSULIN, no direct feedback inhibition (GLUcokinase is a GLUtton. It has a high Vmax because it cannot be satisfied) |
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hexokinase function
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phosphorylates glucose in all other tissues (first step of glycolysis)
NOT induced by insulin, feedback inhibited by glu-6-phos |
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give the rate-determining enzyme:
1. glycolysis 2. gluconeogenesis 3. TCA cycle 4. glycogen synthesis 5. glycogenolysis |
1. PFK-1
2. Fruc-1,6-bisphosphatase 3. isocitrate dehydrogenase 4. glycogen synthase 5. glycogen phosphorylase |
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give the rate-determining enzyme:
1. HMP shunt 2. de novo pyrimidine synthesis 3. de novo purine synthesis 4. urea cycle 5. fatty acid synthesis 6. fatty acid oxidation 7. ketogenesis 8. cholesterol synthesis |
1. G6PD
2. carbamoyl phosphate synthetase II 3. gulatmine-PRPP amidotransferase 4. carbamoyl phosphate synthetase I 5. Acetyl-CoA carboxylase 6. carnitine acyltransferase I 7. HMG-CoA synthase 8. HMG-CoA reductase |
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universal electron acceptors
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B2: flavin nucleotides (FAD+)
B3: nictonamides (NAD+, NADP+) |
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NADPH is used in:
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anabolic processes
respiratory burst P-450 glutathione reductase |
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pyruvate carboxylase v. pyruvate dehydrogenase
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pyruvate carboxylase: pyruvate to oxaloacetate (biotin); replenish TCA or gluconeogenesis
pyruvate dehydrogenase: pyruvate to Acetyl-CoA (thiamine); from glycolysis to TCA cycle |
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Cori cycle
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in liver, allows lactate to become glucose for muscle, RBCs (costs 4 ATP)
shifts metabolic burden to liver |
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purely ketogenic amino acids?
purely glucogenic amino acids? |
lys, leu
met, val, arg, his |
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pyruvate dehydrogenase deficiency
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congenital or acquired (alcoholics with B1 deficiency)
backup of pyruvate and alanine leads to lactic acidosis, neurologic defects |
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electron transport inhibitors
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rotenone
CN- antimycin A CO |
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ATPase inhibitors
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oligomycin
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uncoupling agents
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2,4-DNP
aspirin thermogenin (brown fat) |
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purpose of HMP shunt
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to provide NADPH from glu-6-phosphate
NADPH is required for reductive reactions e.g. glutathione inside RBCs (decreases oxidative damage) also yields ribose for nucleotide synthesis |
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sites of HMP shunt
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lactating mammary glands, liver, adrenal cortex, RBCs
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G6PD deficiency
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due to decreased NADPH in RBCs leading to hemolytic anemia
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what can trigger G6PD deficiency?
what are the microscopic findings? |
STRESS (e.g. infection)
DRUGS (sulfonamides, primaquine, anti-TB agents) Heinz bodies, bite cells |
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hydrophobic amino acids
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ala, ile, leu, val
phe, trp, tyr |
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consequences of high NH4+?
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depletes alpha-ketoglutarate, leading to inhibition of TCA cycle
presents with tremor, slurred speech, vomiting, cerebral edema, blurry vision (remember that this can occur to to ALCOHOLIC liver damage!) |
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derivatives of phenylalanine
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tyrosine, DOPA, dopamine, norepi, epi (in that order)
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derivatives of tryptophan
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niacin to NAD+/NADP+
serotonin to melatonin |
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derivatives of glycine
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porphyrin to heme
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derivatives of arginine
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creatine
urea nitric oxide |
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derivatives of glutamate
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GABA (requires B6)
glutathione |
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give the breakdown product:
1. dopamine 2. norepi 3. epi |
1. HMA
2. VMA 3. metanephrine |
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PKU: mechanism, findings
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decreased phenylalanine hydroxylase or tetrahydrobiopterin cofactor
TYROSINE BECOMES ESSENTIAL findings including MR, growth retardation, fair skin, "mousy" body odor ("disorder of AROMATIC aa metabolism = ODOR") |
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causes of albinism
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1. tyrosinase deficiency (can't synthesize melanin from tyrosine)
2. defective tyrosine transporters can result from lack of migration of neural crest cells |
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homocystinuria mechanisms
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1. cystathionine synthase deficiency
2. decreased affinity of above for B6 3. homocysteine methyltransferase deficiency (uses SAM) |
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homocystinuria findings
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high homocysteine in urine, MR, osteoporosis, tall, kyphosis, atherosclerosis, lens subluxation
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cystinuria mechanism, findings
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defect of renal tubular aa transport of cysteine, ornithine, lys, arg
causes cystine kidney stones (staghorn calculi); treat by alkalinizing urine with acetazolamide |
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maple syrup urine disease
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can't degrade branched amino acids, buildup of alpha-ketoacids in blood (I Love Vermont: Ile, Leu, Val)
causes severe CNS defects, MR, death |
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glycogen storage diseases
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Very Poor Carbohydrate Metabolism (von Gierke, Pompe, Cori, McArdle)
Pompe's trashes the Pump (heart, liver, and muscle) |
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von Gierke's disease: deficient enzyme and findings
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glu-6-phosphatase
severe fasting hypoglycemia, increased blood lactate, hepatomegaly |
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von Gierke v. Cori
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Cori has normal blood lactate levels, deficient enzyme is debranching enzyme (a1,6-glucosidase)
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Niemann-Pick disease (AR)
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sphingomyelinase is deficient ("No Man Picks his nose with his sphinger")
findings are progressive neurodegeneration, hepatosplenomegaly, CHERRY-red spot on macula, foam cells |
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Gaucher disease (AR)
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most common LSD, beta-glucocerebrosidase is deficient
findings are hepatosplenomegaly, aseptic necrosis of femur, bone crises, Gaucher's cells (crumpled macrophages) |
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Hunter's (XR) v. Hurler's (AR)
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both are mucopolysaccharidoses (heparan and dermatan sulfates accumulate in both)
"Hunters see clearly (no corneal clouding) and aim for the X (X-linked recessive)." |
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energy equivalents of 1 gram of the following:
protein carbohydrate fat |
4 kcal
4 kcal 9 kcal |
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what is the order of ATP sources tapped to power exercising skeletal muscle?
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stored ATP
creatine phosphate anaerobic glycolysis oxidative phosphorylation glycogen and FFA oxidation |
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carnitine deficiency
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can't transport LCFAs into mitochondria, resulting in toxic accumulation
causes weakness, hypotonia, HYPOKETOTIC HYPOGLYCEMIA |
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what is substrate for ketone bodies?
to what does brain convert ketones? |
HMG-CoA
2 molecules of Acetyl-CoA |
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how does body survive past three days of starvation?
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priorities: supply glucose to brain and RBCs, preserve protein
muscles degraded in days 1-3, after day 3 hepatic formation of ketone bodies supplies brain and heart (survival time determined by fat stores) |
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what is the function of lipoprotein lipase (LPL)?
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degradation of TG circulating in chylomicrons and VLDL (fatty acids taken up in tissues, remnants taken up in liver)
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major apolipoproteins
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A-I: Activates LCAT
B-100: Binds to LDL receptor, mediates VLDL secretion C-II: Cofactor for LPL B-48: c4ylomicron 8cretion E: mediates Extra (remnant) uptake |
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what is the function of HDL?
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delivers cholesterol from periphery to liver; acts as repository for apoC and apoE (needed for chylomicron and VLDL metabolism)
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what cells secrete chylomicrons?
what apolipoproteins do they use? |
intestinal epithelial cells
uses: apoB48 (c4ylomicron 8cretion) A-IV C-II (Cofactor for LPL) E (Extra/remnant uptake) |
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familial dyslipidemia I v. IIa
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I: hyperCHYLOMICRONS (elevated blood TGs, chole); LPL deficiency
IIa: hyperCHOLESTEROL (elevated blood chole); decreased LDL receptors; AD inheritance |
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what condition results from deficiencies in apoB100 and apoB48?
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abeta-lipoproteinemia (AR inheritance)
failure to thrive, steatorrhea, anathocytosis, ataxia, night blindness |
