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40 Cards in this Set
- Front
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Pyruvate dehydrogenase deficiency |
PDH usually converts pyruvate to acetyl-CoA to enter Krebs cycle. If no PDH, pyruvate will be converted to lactate via lactate dehydrogenase, causing lactic acidosis. Findings: neuro defects, lactic acidosis, high serum alanine. Lysine and Leucine are the only purely ketogenic AAs --> do not lead to lactic acidosis! |
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Hexokinase |
Glucose to G6P In most tissues, but NOT liver or pancreatic beta cells Low Km (active at low concentrations of substrate; high affinity) Low Vmax (decreased capacity) No effect of insulin Feedback inhibited by product! (G6P) Gene mutation NOT associated w/MODY |
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Glucokinase |
Glucose to G6P ONLY in liver and pancreatic beta cells High Km (active at high concentrations of substrate; low affinity) High Vmax (increased capacity; no limit really) Regulated by insulin No feedback inhibition (active regardless of product levels) Gene mutation associated w/MODY |
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3 irreversible steps of glycolysis |
Glucokinase/hexokinase (glucose-->G6P) Phosphofructokinase-1 (F6P-->F1,6bisphosphonate** main regulatory step!) Pyruvate kinase (Phospoenolpyruvate-->pyruvate) |
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4 irreversible of gluconeogenesis |
Pyruvate carboxylase (pyruvate-->oxaloacetate; in mito) Phosphoenolpyruvate carboxylase (oxaloacetate-->phosphoenolpyruvate; in cytosol) Fructose-1,6-bisphosphonate (F1,6BP-->F6P; in cytosol) Glucose-6-phosphotase (G6P-->glucose; in ER) |
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PKU |
Phenylalanine--(BH4 + phenylalanine hydoxylase)--> Tyrosine--(BH4 + tyrosine hydroxylase)--> Dopa--(VitB6)--> Dopamine--(VitC)--> NE--(SAM)--> Epinephrine - PKU due to decr phenylalanine hydroxylase or BH4 (malignant PKU, due to decr dihydropterin reductase). - Tyrosine becomes essential (decr phenylalanine and incr tyrosine in diet) - Phenylketones found in urine - Intellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor |
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Gilbert Syndrome |
Hereditary hyperbilirubinemia Mildly ↓ UDP glucuronosyltransferase activity and ↓ uptake of bilirubin by hepatocytes Asymptomatic/mild jaundice ↑ unconjugated bilirubin |
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Crigler-Najjar, type 1 |
ABSENT UDP glucuronosyltransferase Patients die w/in a few years - jaundice, kernicterus ↑ unconjugated bilirubin Tx: plasmapheresis, phototherapy Type 2 is less severe, responds to phenobarbital |
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Dubin-Johnson Syndrome |
Defective liver excretion ↑ conjugated bilirubin Grossly black liver, benign |
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Rotor Syndrome |
Similar to Dubin-Johnson, but even milder No black liver |
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Irreversible reactions in glycolysis (catalysts) |
Hexokinase/glucokinase Phosphofructokinase-1 Pyruvate kinase |
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Irreversible reactions (catalysts) |
Pyruvate carboxylase Phosphoenolpyruvate (PEP) carboxylase Fructose-1,6-bisphosphonate Glucose-6-phosphatase |
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Pyruvate dehydrogenase |
Mitochondrial enzyme linking glycolysis and TCA cycle (irreversible) Cofactors: TLC For Nancy (Thiamine, Lipoic Acid, Coenzyme A, FAD, NAD) If deficiency = buildup of pyruvate, shunted to lactate and alanine Sx: neuro defects, lactic acidosis, ↑ serum alanine Rx: ↑ ketogenic nutrients (lysine and leucine = ketogenic!, fats) |
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Electron transport inhibitors |
↓ proton gradient and block ATP synthesis Rotenone, Cyanide, CO, antimycin A |
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ATP synthase inhibitors |
Directly inhibit mito ATP synthase ↑ proton gradient Oligomycin |
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Uncoupling agents |
↑ permeability of membrane ↓ proton gradient, ↑ O2 consumption ATP synthesis stops, but electron transport continues HEAT 2,4-dinitrophenol (weight loss), aspirin (high doses), thermogenin in brown fat |
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HMP shunt |
Source of NADPH For reductive reactions (glutathione reductase in RBCs, FA and cholesterol biosynthesis, needed w/NADPH oxidase for neuts and monocytes) Also to make ribose (nucleotide synthesis) No ATP used/produced Oxidative: Glucose-6-P-dehydrogenase (G6PD) Nonoxidative: Phosphopentose isomerase, transketolases, requires B1 (thiamine) (Wernicke-Korsakoff disease: transketolase does not bind B1 well, WK syndrome, give extra thiamine) |
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G6PD deficiency |
NADPH needed to keep glutathione reduced (reduced glutathione detoxifies free radicals and peroxides) ↓ NADPH in RBCs causes hemolytic anemia due to poor RBC defines vs. oxidizing agents and infection Xr, common in blacks (malarial resistance) Heinz bodies (oxidized Hb precipitated in RBCs) Bite cells (due to splenic macros) |
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Essential fructosuria |
Fructokinase deficiency AR Fructose in blood and urine Benign, asymptomatic (fructose not trapped in cells) |
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Fructose intolerance |
Aldolase B deficiency AR Fructose-1-P accumulates in cells, ↓ available phosphate (inhibits gycogenolysis and gluconeogenesis) Sx after weening and when eat fruit, juice, honey Urine dipstick NEG b/c only measures glucose Sx: hypoglycemia, jaundice, cirrhosis, vomiting Rx: ↓ intake of fructose and sucrose |
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Disaccharide composition |
Maltose = Glucose + Glucose Sucrose = Glucose + Fructose Lactose = Glucose + Galactose |
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Galactokinase deficiency |
Galactokinase deficiency, galactitol accumulates if galactose in diet AR Relatively mild Sx: galactose in blood and urine, infantile cataracts |
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Classic galactosemia |
Galactose-1-phosphate uridyltransferase AR G1P and galactitol build up Sx: jaundice, hepatomegaly, infantile cataracts, intellectual disability Rx: exclude galactose and lactose from diet |
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Sorbitol |
Traps glucose in cell by converting to alcohol Osmotic, so water rushes in. Aldose reductase = glucose to sorbitol Sorbitol dehydrogenase = sorbitol to fructose Only (or mainly) aldose reductase: schwann cells, retina, kidneys, lens (primarily) |
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Hyperammonemia |
Acquired or hereditary Excess NH4+, depletes alpha-ketoglutarate, inhibition of TCA cycle Rx: limit protein, benzoate or phenylbutyrate bind AA and lead to excretion (↓ ammonia levels), lactulose (acidifies GIT, traps NH4+ for excretion) ↓ BUN, ↑ ammonia in blood |
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N-acetylglutamate deficiency |
Required cofactor for carbamoyl phosphate synthase I (CO2+NH3 to carbamoyl phosphate) (Same presentation as carb-phos-synthase deficiency, but ↑ ornithine here) ↓ BUN, ↑ ammonia in blood |
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Ornithine transcarbamylase deficiency |
Most common urea cycle disorder (carbamoyl phosphate to citrulline [leaves mito]) XR Body can't eliminate ammonia ↓ BUN, ↑ ammonia in blood, ↑ orotic acid in blood (XR = men more "orotic" than women) |
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Amino acid derivatives (to epinephrine) |
Phenylalanine → tyrosine → dopa (to melanin) → Dopamine → NE → EPI |
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Phenylketonuria |
↓ phenylalanine hydroxylase or ↓ BH4 (tetrahydrobiopterin cofactor) Tyrosine becomes ESSENTIAL (b/c can't make from phenylalanine!) AR ↑ phenylalanine = excess phenylketones in urine Sx: intellectual disability, growth retardation, fair skin, eczema, musty body odour (aromatic aa) Rx: ↓ phenylalanine, ↑ tyrosine in diet Maternal PKU: lack of proper rx = microcephaly, intellectual disability, growth retardation, congenital heart defects |
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Alkaptonuria (ochronosis) |
↓ homogentisate oxidase as tyrosine degraded to fumarate AR, benign DARK CT, brown sclera, black urine on prolonged exposure to air. May have debilitating arthralgia (homogentisic acid toxic to cartilage) |
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Homocystinuria |
Methionine ← Homocystine → Cystathionine → Cystine AR 1) Cystathionine synthase deficiency 2) ↓ affinity of cystathione synthase for pyridoxal phosphate (B6, pyridoxine) 3) Homocysteine methyltransferase (methionine synthase) deficiency Sx: ↑↑↑ homocystine in urine, intellectual disability, osteoporosis, tall, kyphosis, lens subluxation, thrombus and atherosclerosis (MI early in life) |
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Cystinuria |
Defect of renal PCT and intestinal aa transporter for cysteine, ornithine, lysine and arginine (COLA) AR Precipitation of hexagonal cystine stones Rx: urinary alkalinization, chelating agents, good hydration |
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Maple syrup urine disease |
Blocked degradation of branched amino acids "I love Vermont" = isoleucine, leucine, valine ↓ alpha-ketoacid dehydrogenase (B1) AR Urine smells like maple syrup/burnt sugar ↑ alpha-ketoacids in blood (esp leucine) Sx: severe CNS defects, intellectual disability, death Rx: restriction of leucine, isoleucine and valine in diet, thiamine supplementation |
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Alcohol metabolism |
Alcohol → acetylaldehyde → acetate via alcohol dehydrogenase and acetaldehyde dehydrogenase Acetylaldehyde responsible for hangovers Decreased levels of acetaldehyde dehydrogenase in Asians, inhibited by disulfuram |
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Von Gierke disease |
Glucose-6-phosphatase deficiency (reversal of hexokinase) AR Sx: SEVERE fasting hypoglycemia, ↑ glycogen in liver, ↑ blood lactate, hepatomegaly Rx: frequent oral glucose/cornstarch, avoidance of fructose and galactose |
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Pompe Disease |
Lysosomal alpha-1,4-glucosidase deficiency AR Sx: Cardiomyopathy, muscle weakness, early death "Trashes the Pompe" (heart) |
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Cori disease |
Debranching enzyme deficiency (alpha-1,6-glucosidase) AR Sx: milder form of type I, normal blood lactate |
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McArdle Disease |
Skeletal muscle glycogen phosphorylase deficiency AR ↑ glycogen in muscle, but can't b/d! cramps, myoglobulinuria (red urine) w/strenuous exercise, arrhythmia from electrolyte abnormalities NO hepatomegaly "McArdle can't do hurdles" |
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Ketone bodies |
Acetoacetate, beta-hydroxybutyrate (and acetone, no energy) Can make acetyl CoA to be used in TCA Used by brain and muscle Fruity odor to breath Brain fuel use: 1/2-1 day = glycogen up to day 5-7 = gluconeogenesis 1 week+ = ketone bodies (adipose tissue) RBCs lack mitochondria and cannot use ketones!! (glycolysis only) |
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Cholesterol synthesis |
Rate-limiting step catalyzed by HMG-CoA reductase (statins competitively and irreversibly inhibit) |