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110 Cards in this Set
- Front
- Back
Hemolytic anemia causes
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Pyruvate kinase >> phosphoglucose isomerase
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Glycolysis steps regulated (3)
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1 = RDS (PFK), regulated by ATP/citrate/AMP/F26BP; 2 = Pyruvate Kinase, regulated by ATP/alanine/F16BP;3 = Pyruvate deH, regulated by ATP/NADH/acetyl-CoA
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Things required by pyruvate deH (5)
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B1/2/3/5 (thiamine, riboflavin, niacin, panthenate) + lipoic acid (which is inhibited by arsenic); activated by exercise (NAD, ADP, Ca2+)
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Arsenic
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Blocks lipoic acid mediation of Pyruvate deH rxn; rice water stools, garlic breath, vomiting
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Pyruvate deH deficiency
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Pyruvate/alanine buildup -> lactic acidosis; tx with ketogenic diet (LL Kool Jenic, leucine/lysine)
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Pyruvate options (4)
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1 = replenish NAD+ for glycolysis (lactate production);2 = accept NH3 group and become alanine (off to liver for urea production);3 = oxaloacetate (glucogengenesis or TCA intmd);4 = Acetyl-CoA (into TCA; produces CO2 and NADP)
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Cori cycle
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Taking lactate from muscles/RBCs, turning it into pyruvate/glucose in the liver (costs 18 ATP), then shuttling back in blood
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Alpha KG deH
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converts alphaKG into succinyl CoA; Very similar to pyruvate deH (requires same factors); also produces CO2 + NADP; inhibited by ATP/NADH/Succinyl CoA (again, very similar to Pyruvate-deH);
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Oligomycin
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Blocks flow of H+ thru ATPase (increases H+ gradient but decreases ATP production)
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Irreversible step(s) of gluconeogenesis that take place in the mitochondria
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Pyruvate->oxalate (pyruvate carboxylase); requires biotin/ATP; promoted by acetyl-CoA
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Irreversible step(s) of gluconeogenesis in the cytosol
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1: PEP carboxylase converts oxaloacetate to PEP (requires GTP);2: Fructose-1,6-BP converted to F6P by Fructose-1,6-bisphosphatase;
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Irreversible step(s) of gluconeogensis in the ER
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G6P dephosphorylated
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Where can gluconeogenesis occur?
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Kidney, gut epithelium, LIVER
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Things that contribute substrates to gluconeogenesis (4)
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1: lactate; 2: alanine (protein catabolism); 3: Glycerol from adipose tissue; 4: metabolic product (propionyl-CoA) of odd (literally odd-numbered)-chain fatty acids
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PPPathway (HMP Shunt)
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Alternative to glycolysis for G6P; either oxidative rxns or non-oxidative rxns; these are "free" rxns in the cytoplasms that do not consume/generate ATP; most important in sites of synthesis (mammary, liver, adrenal cortex) and RBCs
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Oxidative rxns in PPP
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Key enzyme = G6DP; irreversible; creates NADPH for FA/steroid synthesis and GSSH reduction;
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Non-oxidative rxns in PPP
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Reversible; create glycolytic intermediates (G3P/F6P) and R-5-P for NT synthesis; requires thiamine
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Fructose intolerance
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aldolase B deficiency; causes PO4 "sink" blocking neogenesis, glycogenolysis -> hypoglycemia, jaundice, cirrhosis; must avoid fructose (and sucrose)
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Essential fructosuria
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Can't even metabolize fructose due to fructokinase deficiency; benign condition
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Defect in galactose-1-P uridyltransferase
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Galactosemia; toxic buildup of galactose metabolites -> cataracts/MR/hepatomegaly; avoid galactose (and lactose) in diet
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Defect in galactokinase
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Mild galactosemia; galactitol may appear in urine if galactose ingested
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(exclusively) glucogenic amino acids
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Met Val Arg His
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Gluco+ketogenic amino acids
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Phenylalanine, Tyrosine, Tryptophan, Isoleucine
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How protein-nitrogen gets ready for elimination
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Aminoacids donate NH3 to create glutamate, which hands off NH3 to pyruvate (becomes alanine); alanine travels to liver, where it hands off NH3 to create glutamate, which gives NH3 to urea
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How NH4 gets turned into urea
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Urea cycle: NH4+CO2+2ATP --Carbamoyl phosphate synthase---> CP; CP starts cycle; aspartate enters cycle at some point, and arginine created at some point; end produce of cycle (ornithine) turned into citrulline
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Arginine -->
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Creatinine, urea, Nitric oxide
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Phenylalanine-->Tyrosine ->
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Thyroxine, DOPA (melanin, DA, NE, EPI)
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Glutamic Acid
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GABA (B6-required) and GSH
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Phenylacetate/lactate/pyruvate in urine
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Phenylketonuria (missing phenylalanine hydroxylase), which leads to toxic metabolite buildup + tyrosine becomes essential AA; MR/Growth stunt/musty (aromatic) odor
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Homogentisic acid oxidase
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Deficiency causes black urine upon standing and black CT (alkaptonuria); may cause joint pain, but benign otherwise
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Albinism causes
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Can't get tyrosine into cell or can't convert tyrosine into melanin; failure of NCC migration; skin cancer risk inc.
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Homocystinuria (1/2/3)
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1: can't convert HS into cysteine (cystathionine deficiency/B6); fix by upping cysteine/B12 while decreasing met in diet; 2: decreased affinity of the same enzyme; tx by upping B6; 3: can't convert HS into met (HS methyltransferase deficiency)
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General principles of homocystinuria
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Cysteine becomes essential AA (up diet); MR/osteoperosis/tall stature/atherosclerosis/lens falls into PC
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Cystinuria
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PCT transporter defect; cysteine (hexagonal) stones; tx by alkalinizing urine (acetazolamide) to reduce S-S bonds and inc. solubility
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Maple syrup Dz (alpha ketoacid deH, not to be confused with alpha ketoglutarate deH in the TCA)
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Certain aa's (branched) can't be degraded; in urine, they smell like maple syrup; MR/CNS/death; aa's = isoleucine/valine/leucine;I(soleucine) L(eucine) V(aline) --> ILV = I Love Vermont Maple Syrup!
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AMP broken into adenosine…how does adenosine get back to AMP?
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Adenosine -> inosine -> hypoxanthin -> IMP -> AMP
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GMP broken into guanosine…how does it get back to GMP?
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Guanosine -> guanine -> GMP
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Important enzymes (2) in the AMP cycle
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1: AID converts adenosine to inosine; AID deficiency causes SCID (bubble boy) syndrome; when AMP builds up, ATP/dATP made in excess such that the enzyme that removes the 2' OH group from nucleotides (ribonucleotide reductase) gets inhibited;2: HGPRT converts hypoxanthine to IMP; defect leads to buildup of xanthine/uric acid
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Lesch-Nyhan (purine salvage)
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Self-mutilation, gout, retardation, aggression; HGPRT mutation (X-linked);
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AID Deficiency (purine salvage)
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Can't convert adenosine to inosine, leading to shutting down of NT synthesis and severe (no B/T cells) immunodeficiency; X-linked
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First 4 things the body does (over the first 3 days of food deprivation)
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Use up current supplies (glycogenolysis, gluconeogensis); start breaking down fatty acids; muscle/liver shift to using fat as fuel source; hepatic gluconeogenesis using catabolic substrates (i.e. alanine) and fat products (odd chain breakdown + glycerol)
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Insulin-sensitive glucose transport
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GLUT4 in muscle/fat
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GLUT1
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Brain/RBC
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GLUT2
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Pancreas, kidney, liver
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Electrolyte FX of insulin (2)
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Shift K+ into cells and increase Na+ retention at kidneys
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Glycogen defects: I
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Glucose-6-phosphatase missing so liver can't release glucose; hepatomegaly/hypoglycemia; blood lactate increased (acidosis); Von Gierke's
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Glycogen defects: II
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Heart eruption (Pompeii); cardiomegaly caused by inability to breakdown residual glycogen in lysosomes (a1,4 glucosidase); leads to early death
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Glycogen defects: 3
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Cori; missing a-1,6 debranching enzyme, so glycogen is useless; mild version of type 1 (lower lactate levels)
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Glycogen defect: 5
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McArdle's in the muscle; missing glycogen phosphorylase, so can't break down glycogen; exercise intolerance that can lead to myoglobinuria
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Form of glucose that is added to glycogen
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Glucose-UDP
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Hepatosplenomegaly, the bends of femur, macrophages that look like crumpled tissue paper
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Buildup of glucocerebrosidase (Beta enzyme deficiency), mc problem; Gaucher's
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Tay-Sach's
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Tay SaX (hexosamidase defect -> GM2 buildup); cherry red spot on retina, MR, onion lysosomes; Ashkenazi Jews
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Neimann-Pick (look at the belly!)
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Sphingomyelin buildup; FTDementia; also seen with cherry red spots, but it is macular in location; also, GI MEGALY; with foam cells
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Krabbe's
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Confluent loss of WM (demyelination); buildup of ceramides (defect in galactocerebrosidase); peripheral neuropathy + globoid cells + optic atrophy
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Ashkenazi roundup:
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GI megaly + cherry spot = Pick's
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GI megaly + cherry spot =
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GI megaly + bone findings = Gaucher's
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GI megaly + bone findings =
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Cherry spot + developmental delay = Tay-Sach's
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Cherry spot + developmental delay =
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tay sachs
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Central and peripheral nervous findings; ataxia + dementia
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Arylsulfatase deficiency (cerebrosidase accumulation) seen in MLD
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Corneal clouding (anterior eye finding) + gargoylism + airway obstruction (breathe!) + dev't delay
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Mucopolysacch def (Hurler's); iDuron (alpha deficiency); heparan sulfate builds
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Mild gargoylism + aggressive = awesome! No clouding of corneas
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Hunter's; X-linked; iDuron (iduron sulfatase)
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X-linked storage Dos
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Hurler's, Fabry's
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Renal glomerular findings; purple splotches; LVH; corneal crap; peripheral neuropathy
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Fabry's (alpha galactosidase, ceramide trihexoside)
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Familial hyperlipidemias (I, IIa, IV)
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1: elevated chol/TG (chylomicrons up due to LPL/CII defect);2a: elevated chol due to decreased LDL receptors at liver;4: elevated TG due to increased VLDL production
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apoAI
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Activates LCAT
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Apo48
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Chylomicrons
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Essential fatty acids
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Linoleic acid and linolenic acid (need these for eicosanoids)
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Roles of citrate and carnitine in fatty acid metabolism
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Citrate shuttles Acetyl-CoA out of the mitochondria for FA synthesis; carnitine brings long-chain FAs into the mitochondria for beta oxidation
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HMG CoA --> mevalonate
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Catalyzed by HMG CoA Reductase (statins)
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Malonyl-CoA
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Intermediate in FA synthesis; inhibits shuttling of FAs back into mito for destruction
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Pb2+ FX on heme synthesis
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Blocks 2 steps in mitochondria: ALA dehydratase (export to cytoplasm) and ferrochelatase (adding Fe to protoporphyrin)
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Acute intermittent porphyria
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Can't convert urobilinogen to uroporphyrinogen in cytoplasm
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Porphyria cutanea tarda
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Can't get things back into mitochondria (decarboxylase enzyme affected);
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Tea colored urine; dALA + Coproporphyrin; dALA + Prophobilinogen
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Cutanea tarda, Pb poisoning, acute intermittent porphyria
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General problem with porphyrias
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Not enough heme --> microcytic anemia; intermediate accumulation leads to clinical symptoms (PPPPP);Abd pain!;Urine findings (pink);Polyneuropathy;Psyche changes;Precipitation via drugs
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Heme--> _____ --> ______ -->
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Heme, biliverdin, bilirubin, urobilinogen, urobilin (renal excretion)
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Aldolase B vs Aldolase Reductase
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Aldolase B is defective in Fructose intolerance (the worse of the 2 fructose problems); Aldose reductase is the lesser of the two galactosemias (galactokinase deficiency)
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Thiamine-dependent (B1)
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Non-oxidative rxns of PPP; production of acetyl CoA (pyruvate deH); production of succinyl-CoA (alphaKG deH); branched-chain AA degradation (maple syrup Dz, alpha ketoacid deH def)
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Biotin-dependent (decarboxylation)
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Pyruvate --> oxaloacetate (Pyruvate carboxylase for gluconeogenesis); malonyl-CoA --> fatty acid synthesis in cytoplasm;Production of MethylmalonylCoA from propionyl-CoA
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Carbamoyl Phosphate Synthase
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RDS of urea cycle
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Three uses of NADPH
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Steroid synthesis, GSH reduction, P450 metabolisms
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Steps in Glycolysis that cost ATP
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Hexokinase and PFK-1
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Steps in glycolysis that produce ATP
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Phosphoglycerate kinase and pyruvate kinase (the step that makes pyruvate)
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Steps of glycolysis which are regulated
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3rd (RDS) and the last two (pyruvate creation and acetyl-CoA creation)
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B6 depletion or carcinoid syndrome may cause which clinical symptoms?
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Pellagra (diarrhea, dermatitis, mental changes); Niacin deficiency
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B6 deficiency
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Irritability, anemia, convulsions
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B5 deficiency
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Alopecia, dermatitis, enteritis
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B2 deficiency
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Cheilosis, corneal vascularization, angular stomatitis (FACE)
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B1 def
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Wernickes or Beri Beri (Wet = dilated CHF, dry = neuropathy, symmetrical muscle atrophy)
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Anything involved CoA also involves…
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B5 (pantotheone)
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VitC helps collagen, but also (2)
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Helps absorb Fe2+ and helps convert DA to NE
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VitE
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Antioxidant in RBCs
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Less hormone-induced hair, hypogonadism
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Zinc deficiency
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B6 uses
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Making heme, glycogen phosphorylase; plays a role in homocysteinuria (helps overcome enzyme affinity decrease)
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HS + CH3 --> _____, mediated by what
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Methionine, mediated by THF-CH3 + B12
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B12 deficiency causes neuropathy when what accumulates
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Met down or methylmalonyl-CoA up (can't enter Kreb's cycle at succinyl CoA)
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Steps in glycolysis that produce ATP
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Phosphoglycerate kinase and pyruvate kinase (the step that makes pyruvate)
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Steps of glycolysis which are regulated
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3rd (RDS) and the last two (pyruvate creation and acetyl-CoA creation)
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B6 depletion or carcinoid syndrome may cause which clinical symptoms?
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Pellagra (diarrhea, dermatitis, mental changes); Niacin deficiency
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B6 deficiency
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Irritability, anemia, convulsions
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B5 deficiency
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Alopecia, dermatitis, enteritis
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B2 deficiency
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Cheilosis, corneal vascularization, angular stomatitis (FACE)
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B1 def
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Wernickes or Beri Beri (Wet = dilated CHF, dry = neuropathy, symmetrical muscle atrophy)
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Anything involved CoA also involves…
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B5 (pantotheone)
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VitC helps collagen, but also (2)
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Helps absorb Fe2+ and helps convert DA to NE
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VitE
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Antioxidant in RBCs
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Less hormone-induced hair, hypogonadism
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Zinc deficiency
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B6 uses
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Making heme, glycogen phosphorylase; plays a role in homocysteinuria (helps overcome enzyme affinity decrease)
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HS + CH3 --> _____, mediated by what
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Methionine, mediated by THF-CH3 + B12
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B12 deficiency causes neuropathy when what accumulates
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Met down or methylmalonyl-CoA up (can't enter Kreb's cycle at succinyl CoA)
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