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121 Cards in this Set
- Front
- Back
Acetyl CoA from the ___ moves into the ___ via the ___ shuttle, where it combines with CO2/biotin to form ___-CoA for FA synthesis.
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mitochondria, cytoplasm, citrate shuttle, Malonyl-CoA
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What is the enzyme that catalyzes the reaction: FA + CoA --> Fatty acyl CoA?
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Fatty acyl CoA synthetase (durr.)
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What is the role of carnitine?
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Carnitine transports long chain FAs (like coenzyme A) into mitochondria
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What step in FA degradation does malonyl CoA inhibit?
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Malonyl CoA inhibits carnitine shuttle from moving FA from cytoplasm to mitochondria (recall: insulin inc. production malonyl-CoA)
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What happens if you are missing part of the carnitine shuttle?
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Can't use long chain FA as metabolic fuel in skeletal muscle, causing myoglobinemia and weakness following exercise
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Under what situations would you find ketone bodies?
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1) diabetic ketoacidosis
2) prolonged starvation |
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Which organs utilize ketone bodies?
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1) muscle
2) brain |
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Where are ketone bodies made, and from what substrate?
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Liver; HMG-CoA
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HMG-CoA --> ___ --> ___
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acetoacetate --> Beta-hydroxybutyrate
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Where does HMG-CoA come from?
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Acetyl-CoA --> acetoacetyl-CoA --> HMG-CoA
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Ketone bodies are metabolized by the brain to 2 molecules of:
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acetyl CoA
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Someone in ketoacidosis has breath that smells:
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fruity
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What is the rate limiting step in cholesterol synthesis?
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HMG-CoA --> mevalonate, via enzyme HMG-CoA reductase
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Which group of drugs inhibits HMG-CoA reductase?
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Statins, like Lovastatin
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What does LCAT stand for?
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lecithin cholesterol acyltransferase, which esterifies plasma cholesterol
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Which enzyme degrades your dietary TGs --> FFAs in the small intestine?
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pancreatic lipase
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Intestinal epithelial cells convert FFAs back into ___ and package them into ___.
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TGs, chylomicrons
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Chylomicron = TG + ___ + ___ + ___ + ___.
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E, A, C-II, B-48
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Which enzyme degrades chylomicrons and VLDL?
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lipoprotein lipase
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Chylomicron remnant is taken up by liver which puts out VLDL, consisting of:
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VLDL = TG + CE + E + B-100 + C-II
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What does hepatic TG lipase degrade?
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the remaining TG left in IDL
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LDL = ___ + ___.
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CE + B-100
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B-100 on LDL and IDL binds to:
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LDL receptor on Liver surface
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What enzyme degrades the TG stored in adipocytes?
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hormone-sensitive lipase
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What is "A" on the surface of a chylomicron?
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activates LCAT
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What is C-II on the surface of chylomicron & VLDL?
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cofactor for lipoprotein lipase (recall: this enzyme degrades chylomicrons & VLDL)
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What is the "E" on surface of chylomicron, remnant, VLDL, IDL?
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mediates "extra" (remnant) uptake -- whatever that means.
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What is the role of chylomicron?
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deliver TGs to tissues and Cholesterol to liver
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What happens if you have excess chylomicrons?
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pancreatitis, lipemia retinalis (creamy white vessels), eruptive xanthomas
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What is the role of VLDL?
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deliver liver TGs to tissues
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What happens if you have excess VLDL?
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pancreatitis
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B-48 and B-100 mediate ___ of chylomicrons and VLDL, respectively.
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secretion
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Which lipoprotein delivers TGs and Cholesterol to the liver?
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IDL
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Which lipoprotein delivers hepatic Cholesterol to peripheral tissues?
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LDL
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Excess LDL causes:
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atherosclerosis, xanthomas, arcus cornea (white/gray opaque ring around edge of cornea)
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What does HDL do?
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reverse Ch transport, from tissues --> Liver, also is storage for apoC and apoE which are needed for chylomicron and VLDL metabolism (recall: C-II cofactor for lipoprotein lipase, "E" for remnant uptake)
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Where is HDL secreted from?
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liver, intestine
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Which apolipoprotein helps form structure of HDL?
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apoA (recall: A-I activates LCAT)
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Which lipoproteins carry most of the body's cholesterol?
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LDL, HDL
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Type 1 hyperchylomicronemia
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lipoprotein lipase deficiency or altered cofactor C-II; inc. chylomicrons, inc. TG & Cholesterol
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Type 2a hypercholesterolemia
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dec. LDL receptors; inc. LDL, inc. Cholesterol
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Type 2b combined hyperlipidemia
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liver overproduction of VLDL; inc. VLDL & LDL; inc. TG & Cholesterol
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Type 3 dysbetalipoproteinemia
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altered apoE; inc. IDL & VLDL; inc. TG & Cholesterol
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Type 4 hypertriglyceridemia
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liver overproduction of VLDL; inc. VLDL only; inc. TG
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Type 5 mixed hypertriglyceridemia
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inc. production/dec. clearance of VLDL & chlyomicrons; inc. VLDL & chylomicrons; inc. TG & Cholesterol
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Heme synthesis:
Start with succinyl CoA + Glycine --> ... --> HEME |
succinyl CoA + Gly --> ALA (committed step, ALA synthetase) --> porphobilinogen --> preuroporphyrinogen --> uroporphyrinogen III --> coproporphyrinogen --> protoporphyrin (+ Fe) --> HEME
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Acute intermittent porphyria affects which step in heme synthesis?
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porphobilinogen --> pre-uroporphyrinogen
* missing enzyme uroporphyrinogen I synthetase, porphobilinogen & ALA accumulate in urine |
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Porphyria cutanea tarda affects which step in heme synthesis?
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uroporphyrinogen III --> coproporphyrinogen
* missing enzyme uroporphyrinogen decarboxylase, uroporphyrin accumulates in urine (tea colored), photosensitivity |
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Lead poisoning affects which 2 steps in heme synthesis?
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inhibits ferrochelatase and ALA dehydrase; coproporphyrin and ALA accumulate
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5 sxs of porphyrias:
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1) painful abdomen
2) pink urine (dk brown...?) 3) polyneuropathy 4) psychological disturbances 5) precipitated by drugs * do not give barbiturates! |
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Heme degradation:
HEME --> ___ --> ___ |
biliverdin --> bilirubin (toxic to CNS and carried by albumin)
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Bilirubin is carried to the ___ where it is conjugated to ___ and excreted in ___.
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liver, glucuronate, bile
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___ is the intestinal intermediate of bilirubin, some of which is reabsorbed and peed out.
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Urobilinogen
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Which form of Hb has low affinity for O2? Which has high affinity?
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T/taut = low
R/relaxed = high |
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Hb exhibits positive ___ and negative ___ which accounts for its sigmoid O2 dissociation curve.
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cooperativity, allostery
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What has 200x the affinity for Hb than oxygen?
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carbon monoxide
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What are 5 things that favor the T/taut form of Hb?
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1) inc. chloride
2) low pH 3) CO2 4) 2,3-BPG 5) temperature |
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Fetal Hb has ___ affinity for 2,3-BPG than adult Hb, thus has higher affinity for oxygen.
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lower
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What is methemoglobin?
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oxidized form of Hb (ferric, Fe3+) that does not bind O2 well but HIGH affinity for CN-
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What do you give in cyanide poisoning?
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Give nitrites to oxidize Hb into methemoglobin, to mop up CN.
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How do you Tx methemoglobinemia?
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methylene blue
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CO2 binding favors the ___ form of Hb to promote ___.
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T form, O2 unloading
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CO2 is transported from tissues to lungs mainly in the form of:
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bicarbonate
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What is PCR used for?
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make many copies of a desired fragment of DNA
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What is involved in a Southern blot?
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DNA sample, labelled DNA probe that anneals to its complementary strand in the sample
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What is involved in a Northern blot?
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RNA sample, radioactive DNA probe
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What is involved in a Western blot?
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protein sample, labelled antibody bind to relevant protein
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What does an ELISA test for?
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antigen:antibody reactivity (patient's blood probed with either test Ag to see if immune system recognizes it, or test Ab to see if certain Ag present)
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How are ELISA's sensitivity and specificity?
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close to 100% (awesome)
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How does ELISA indicate a positive test result?
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peroxidase enzyme generates color change in solution
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Pleiotropy =
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1 gene has > 1 effect on phenotype
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Imprinting =
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differences in phenotype depend on if mutation was maternal or paternal origin
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Loss of heterozygosity =
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1st hit is mutation in tumor suppressor gene.
2nd hit knocks out remaining allele. Cancer develops. |
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Dominant negative mutation =
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heterozygote makes nonfunctional/altered protein that prevents normal gene product from functioning
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Mosaicism =
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when cells in the body have different genetic makeup
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Locus heterogeneity =
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mutations at different loci produce same phenotype (albinism)
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Linkage disequilibrium =
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tendency for certain alleles at 2 linked loci to be inherited more often than expected by chance (occurs in POPULATIONS not families)
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4 rules of Hardy-Weinberg =
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1) no mutations
2) no selection of genotypes 3) random mating 4) no migration in/out |
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Auto dominant disorders:
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- many generations
- males and females - often structural genes - often present after puberty |
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Auto recessive disorders:
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- often due to enzyme deficiencies
- usu. seen in only 1 generation - usu. present in childhood |
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X-recessive disorders:
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- no male to male transmission
- sons of heterozygote moms have 50% chance affected - usu. more severe in males - heterozygote females MAY be affected |
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X-dominant disorders:
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- transmitted thru both parents
- all daughters of affected male are diseased * hypophosphatemic rickets! |
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Mito inheritance:
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- only thru mother
* Leber's hereditary optic neuropathy, mitochondrial myopathies |
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Adult Polycystic Kidney disease presents with:
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pain, hematuria, HTN, progressive renal failure
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Mutation in Adult Polycystic Kidney disease:
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chromosome 16, APKD1
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Adult Polycystic Kidney disease is associated with: (3)
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- berry aneurysms
- polycystic liver dz - mitral valve prolapse |
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Familial hypercholesterolemia (hyperlipidemia type IIa) has elevated ___ due to defective ___.
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LDL, LDL receptors
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Homozygotes with familial hypercholesterolemia have cholesterol ~ ___ and what sxs (3)?
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700, with severe atherosclerosis early, tendon xanthomas, MI maybe by age 20
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Marfan's syndrome is a mutation in which gene?
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fibrillin
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What does Marfan's syndrome look like?
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tall, long extremities, hyperextensive joints; aortic incompetence and dissecting aortic aneurysms; subluxation of lens
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Neurofibromatosis 1 (von Recklinghausen) findings:
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cafe au lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas), scoliosis, pheochromocytoma
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What are si/sx of NF2?
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bilateral acoustin neuroma, optic pathway gliomas, juvenile cataracts
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Where do you see ash leaf spots, facial lesions (adenoma sebaceum), cortical and retinal hamartomas, seizures, mental retardation, renal cysts, cardiac rhabdomyomas?
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tuberous sclerosis
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What auto dominant disease has hemangioblastomas of retina/medulla/cerebellum and multiple bilateral renal cell carcinomas?
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von Hippel-Lindau disease (VHL gene on ch3)
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What is the genetic defect with Huntington's?
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CAG triplet expansion on ch4
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How does Huntington's present?
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depression, progressive dementia, chorea, caudate atrophy, low GABA and Ach, onset ~ 20-50 yrs
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What happens in Familial adenomatous polyposis?
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colon covered with adenomatous polyps after puberty --> colon cancer unless resected
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Where is the deletion in FAP?
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ch5
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What is the molecular defect in achondroplasia?
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cell signalling defect with fibroblast growth factor 3 receptor
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Name 11 autosomal dominant diseases:
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1) adult polycystic kidney
2) familial hypercholesterolemia 3) Marfan's 4) NF1 5) NF2 6) tuberous sclerosis 7) von Hippel-Lindau 8) Huntington's 9) FAP 10) Hereditary spherocytosis 11) achondroplasia |
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Name 11 autosomal recessive diseases:
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1) cystic fibrosis
2) albinism 3) juvenile polycystic kidney 4) a1-antitrypsin deficiency 5) PKU 6) thalassemias 7) sickle cell anemia 8) glycogen storage disease 9) hemochromatosis 10) mucopolysaccharidoses (except Hunter's) 11) sphingolipidoses (except Fabry's) |
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What is the problem with cystic fibrosis and how do you Dx?
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defective Cl- channel (CFTR ch7) --> thick mucus plug lungs, liver, pancreas --> recurrent lung infections, pancreatic insufficiency [Dx high Cl- in sweat test]
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Which 2 bacteria species commonly infect ppl with cystic fibrosis?
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Pseudomonas, S. aureas
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Why are ppl with cystic fibrosis infertile?
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absent vas deferens
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How do you Tx cystic fibrosis?
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N-acetylcysteine to loosen mucous plugs
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Name 10 X-recessive diseases:
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1) fragile X
2) Duchenne's musc. dystrophy 3) hemophilia A&B 4) Fabry's 5) Hunter's 6) G6PD deficiency 7) ocular albinism 8) Lesch-Nyan 9) Bruton's agammaglobulinemia 10) Wiskott-Aldrich |
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What is the genetic defect in Duchenne's muscular dystrophy?
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frame shift --> deletion in dystrophin gene --> accelerated muscle breakdown
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What disease manifests ~ 5yrs old with weakness in proximal limbs and pseudohypertrophy of calves?
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Duchenne's muscular dystrophy
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You can Dx muscular dystrophies with inc. ___ and a muscle biopsy.
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Creatine Phosphokinase (CPK)
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What is Beckers muscular dystrophy?
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milder Duchenne's with less severe mutation in dystrophin
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What disease presents with mental retardation, big jaw, big testes, everted ears?
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Fragile X syndrome - CGG triplet repeat (2nd most common cause of genetic mental retardation)
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Name 4 diseases that have triple repeat expansions:
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1) Huntington's (CAG)
2) Friedrich's ataxia (GAA) 3) myotonic dystrophy (CTG) 4) fragile X (CGG) |
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What are the 7 most common congenital malformations?
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1) heart defect
2) hypospadias 3) spina bifida 4) anencephaly 5) cleft lip 6) hip dislocation 7) pyloric stenosis |
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What are 3 autosomal trisomies?
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1) Down's (21)
2) Edwards (18) 3) Patau's (13) |
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What do you find with Down's syndrome?
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1) mental retardation
2) flat face 3) simian crease 4) heavy epicanthal folds 5) duodenal atresia 6) septum primum ASD 7) inc. risk ALL |
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What are signs of Edwards syndrome?
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1) severe mental retardation
2) rocker bottom feet 3) small jaw 4) low set ears 5) clenched hands 6) congenital heart problem 7) prominent occiput 8) death by 1 yr |
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What are signs of Patau's?
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1) severe mental retardation
2) small eyes 3) small head 4) cleft lip/palate 5) polydactyly 6) congenital heart problem 7) abnormal forebrain 8) death by 1 yr |
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What is Cri-du-chat?
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deletion of 5p, small head, mental retardation, high pitched crying, epicanthal folds, heart abnormalities (like VSD!)
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What is 22q11 syndromes? (CATCH-22)
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1) cleft palate
2) abnormal facies 3) thymic aplasia 4) cardiac defect 5) hypocalcemia 6) microdeletion ch22q11 |
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Alcohol has highest risk of being teratogen at what time of gestation?
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3-8 weeks --> mental retardation, small head, face abnormalities, limb dislocation, heart & lung fistulas
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What is the #1 cause of congenital malformations in the US?
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fetal alcohol syndrome
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