First Aid: Biochemistry

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flucas
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158260
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First Aid: Biochemistry
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2012-06-11 21:11:45
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First Aid Biochemistry step
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First Aid: Biochemistry plus OHSU lecture material
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  1. What is the causes decreased ATP production by mitochondria who have a high proton gradient?
    • cytochrome complex V deficiency
    • i.e. mitochondrial cytochrome ATPase deficiency
  2. What are the signs of uncoupling agent exposure?
    • 1. decreased mitochondrial inner membrane permeability
    • 2. decreased intermembranous space proton gradient
    • 3. decreased ATP production (hypoxia)
  3. What compounds inhibit cytochrome complex IV? What are their effects?
    • cyanide (CN)
    • carbon monoxide (CO)

    uncoupling agents: decreased ATP production
  4. At which cytochrome complex does NADH enter the electron transport chain? How many ATP does it produce?
    Cytochrome complex I

    3 ATP produced
  5. At which cytochrome complex does FADH2 enter the electron transport chain? How many ATP does it produce?
    Cytochrome complex II

    2 ATP produced
  6. What does (salivary) amylase metabolize?
    starch --> maltose
  7. Where are disaccharides mainly metabolized? What are produced?
    brush border of small intestine

    • disaccharides --> monosaccharides
    • sucrose --> glucose + fructose
    • lactose --> glucose + galactose
    • maltose --> glucose + glucose
  8. What is the rate limiting enzyme of glycolysis?
    • PFK: phosphofructokinase
    • same for anaerobic and aerobic pathways
  9. What makes glucokinase different from hexokinase?
    • metabolizes glucose only (vs glucose and fructose)
    • liver only (vs everywhere)
    • decreased substrate affinity
    • increased Km
    • increased Vmax
    • no feedback inhibition

    ultimate regulator of blood glucose levels
  10. How are glucokinase and hexokinase similar?
    • = kinases
    • add phosphate group to glucose
    • glucose --> G6P
  11. What are 3 glycolysis-unique enzymes that are non-reversible?
    • glucokinase/hexokinase: glucose --> G6P
    • PFK: G6P --> PEP
    • pyruvate kinase: PEP --> pyruvate
  12. What is the net yield of anaerobic respiration?
    • per 1 glucose:
    • 2 ATP
    • 2 lactate
    • 2 NAD+
  13. What is the net yield of aerobic metabolism?
    total per 1 glucose = 38 ATP

    • 1 glucose --> 2 pyruvate (4x2 = 8 ATP)
    • 1 pyruvate --> 1 AcetylCoA (1 NADH = 3 ATP)
    • 1 AcetylCoA --> TCA (3 NADH + 1 FADH2 + 1 GTP = 12 ATP)
    • 1 pyruvate --> TCA = 4 + 3 + 12 = 19 ATP

    1 glucose = 2 pyruvate = 19x2 = 38 ATP
  14. What are the cofactors for pyruvate dehydrogenase and a-ketoglutarate dehydrogenase?
    • Vit. B1, B2, B3, B5 = thiamine pyrophosphate
    • lipoic acid
  15. What is the rate limiting step of the TCA cycle?
    • a-ketoglutarate dehydrogenase
    • a-ketoglutarate --> succinyl CoA
  16. How does the NADH from glycolysis enter the mitochondria for use in the TCA cycle?
    malate aspartate shuttle (no ATP used)

    glycerol-3-phosphate shunt (2 ATP used)
  17. What is the net yield per glucose molecule whose products enter the TCA cycle via the glycerol-3-phosphate shunt?
    36 ATP

    (38 ATP generated normally - 2 ATP used by G3P shunt)
  18. Where does glycolysis take place?
    in the cytosol of a cell
  19. What can be used as a substrate for gluconeogenesis?
    • lactate --> Kori Cycle (liver)
    • triglycerides --> glycerol (not FA) --> DHAP
    • proteins --> amino acids (e.g. alanine) --> oxaloacetate

    universal substrate = pyruvate
  20. Which amino acids are exclusively ketogenic?
    • lysine
    • leucine
  21. What are the 2 main products of glycerol metabolism?
    • glycolysis substrate: DHAP
    • phospholipids
  22. How does fructose enter glycolysis?
    • 1. fructokinase + aldolase --> PEP
    • 2. hexokinase --> F6P --> PEP
  23. How does galactose enter glycolysis?
    galactokinase + UDP
  24. What is the rate-limiting enzyme of gluconeogenesis?
    pyruvate carboxylase: pyruvate --> oxaloacetate
  25. What are gluconeogenesis-unique enzymes?
    • pyruvate carboxylase (rate-limiting): pyruvate --> OAA
    • phosphoenolpyruvate carboxykinase: OAA --> PEP
    • glucose-6-phosphatase: G6P --> glucose
  26. What are the main enzymes, substrates, and products of the pentose phosphate pathway?
    G6P dehydrogenase: G6P --> ribose-5-P + NADPH

    • products:
    • nucleotide synthesis substrate: ribose-5-P
    • fatty acid synthesis substrate: NADPH
    • reducing agent for glutathione (i.e. makes reduced glutathione): NADPH
  27. What type of linkages are present in glycogen?
    alpha-1:4 glucose linkages
  28. What are the 2 main enzymes involved in glycogen synthesis?
    • 1. glycogen synthase: induces alpha-1:4 glucose linkages
    • 2. branching enzyme: induces alpha-1:6 linkages

    (many) glucose --> (many) G6P + UDP --> glycogen
  29. What are the 3 main enzymes of glycogenolysis?
    • 1. glycogen phosphorylase: breaks alpha-1:4 linkages (makes mini branches)
    • 2. debranching enzymes: breaks alpha-1:6 linkages
    • 3. alpha-glucosidase: breaks alpha-1:4 linkages
  30. What is the rate-limiting step of glycogen synthesis?
    glycogen synthase
  31. What is the rate limiting step for glycogenolysis?
    glycogen phosphorylase
  32. What is the glycolysis intermediate that is required for glycogen synthesis?
    glucose-6-phosphate
  33. Which enzymes are involved in the formation of the "respiratory burst" and ClOH in immune responses? Which neutralize it?
    • formation of ROS:
    • NADPH oxidase (--> chronic granulomatous disease)

    • neutralization of ROS into hydrogen peroxide:
    • superoxide dismutase (SOD)

    • formation of ClOH from hydrogen peroxide:
    • myeloperoxidase (MPO)

    • prevention of ClOH formation:
    • 1. catalase
    • 2. reduced glutathione
  34. What are the biochemical roles of reduced glutathione? What diseases are related to its function?
    • reduced glutathione:
    • 1. converts hydrogen peroxide to non-reactive products
    • 2. prevents oxidative damage

    • disease: G6PD deficiency --> decreased reduced glutathione
    • --> hemolytic anemia
  35. Which carbohydrate metabolism enzymes deficiencies can result in hemolytic anemia?
    • G6PD deficiency (X-link)
    • pyruvate kinase deficiency (AR)
  36. Which enzyme-based diseases generally result in cataracts?
    • galactokinase deficiency (galactose)
    • homocystinuria
    • aldolase deficiency (sorbitol)
  37. What are the 2 main symptoms of glycogen storage diseases?
    • hepatosplenomegaly
    • hypoglycemia / low blood sugar
  38. What enzyme/reaction is deficient in Von Gierke's disease?
    • glucose-6-phosphatase
    • G6P --> glucose
    • e.g. glycogen storage disease

    s/s: very severe, hypoglycemia, hepatosplenomegaly
  39. What enzyme/reaction is deficient in MacArdle's disease?
    • glycogen phosphorylase
    • glycogen --> G6P
    • e.g. glycogen storage disease

    s/s: exercise fatigue, mild glycogen build-up, muscle cramps
  40. What would you expect if a liver biopsy revealed glycogen made of long chains without alpha-1:6 linkages?
    • branching enzyme deficiency
    • i.e. defect in glycogen synthesis
  41. What is Cori's disease?
    • glycogen storage disease
    • debranching enzyme deficiency
    • decreased glycogen utilization
  42. What is Pompe's disease?
    • glycogen storage disease
    • deficiency in alpha glucosidase enzyme
    • decreased glycogen utilization
    • decreased alpha-1:4 link breaks

    s/s: "Pump" problems (i.e. heart disease)
  43. What is the first site of triglyceride metabolism?
    stomach: lipase
  44. What are the sites and enzymes involved in triglyceride metabolism?
    • stomach: lipase (TG --> FFA)
    • duodenum: bile salt (emulsify)
    • small intestine: pancreatic lipase (emulsify)
    • small intestine: micelle formation and absorption
  45. What are emulsified into mixed micelles?
    • fatty acids
    • cholesterol
    • fat-soluble vitamines (K,A,D,E)
    • bile salts
    • phospholipids
  46. How are medium- and long-chained fatty acids absorbed?
    mixed micell formation --> gut absorption

    • MCFA: passive diffusion into blood --> portal vein
    • LCFA: chylomicrons --> lymph --> thoracic duct --> blood
  47. How do LCFA enter the mitochondria?
    carnitine shuttle
  48. What are the chylomicron "markers"?
    • B48
    • C2
  49. Which tissues receive triglycerides and/or cholesterol from chylomicrons? Which enzyme catalyzes the reaction?
    • capillary endothelial tissue
    • muscles
    • adipose

    via lipoprotein lipase (from chylomicron)
  50. How does acetylCoA exit the mitochondria to participate in fatty acid synthesis?
    citrate shuttle
  51. What is the product of fatty acid beta-oxidation that enters the mitochondria and how does it do it?
    • product for transfer to mitochondria: acylCoA
    • via LCFA carnitine shuttle
    • cofactor: CATI
  52. What is the rate limiting enzyme of fatty acid synthesis?
    acetylCoA carboxylase: acetylCoA --> malonylCoA
  53. What is the rate limiting step of cholesterol synthesis?
    HMG CoA reductase: acetylCoA --> mavulonic acid
  54. What are the potential fates of acetylCoA?
    • 1. (massive) ATP production via TCA
    • 2. cholesterol synthesis via HMG CoA reductase
    • 3. fatty acid synthesis via acetylCoA carboxylase
    • 4. ketone synthesis via HMG CoA synthase
  55. What are ketones that the body uses for energy and how are they made?
    • acetoacetate
    • 3-beta-hydroxybutyrate

    • = alternative fuel source vs glucose
    • products of fatty acid breakdown via beta-oxidation
    • TG --> FA --> acylCoA --> acetylCoA --> ketones
    • HMG CoA synthase: acetylCoA --> ketones
  56. What is the net yield per each cycle of TCA?
    • 3 NADH
    • 1 FADH2
    • 1 GTP

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