1. Carbohydrate Catabolism I Chapter 14 and parts of 15 March 5, 2015 BC368 Biochemistry of the Cell II

2. Catabolism

3. Central Role of Glucose

4. Overview of glycolysis

5. Two phases of glycolysis

7. Preparatory Phase Fig 14-2

8. pg 526 Reaction 1: phosphorylation

9. Fig 14-3

10.  Tissue-specific isozymes. Hexokinase vs. glucokinase Fig 15-14

11. Reaction 2: isomerization aldose ketose

12. Reaction 2: isomerization Fig 14-3

13. Reaction 3: phosphorylation

14. Fig 14-3

15. Reaction 4: cleavage

16. Fig 14-3

17. Reaction 5: isomerization

18. Fig 14-3

19. Keeping Track of Carbons glucose G3P

20. Fig 14-2

21. Reaction 6: oxidation

22. Fig 14-3

23. Reaction 7: substrate level phosphorylation

24. Reaction 8: shift of phosphoryl group

25. Fig 14-3

26. ~Fig 14-8 Fig 14-9

27. Reaction 9: dehydration

28. Reaction 10: substrate level phosphorylation

29. https://www.youtube.com/watch?v=EfGlznwfu9U Energy investment Cleavage Energy Harvest Summary

30. Efficiency

31. Feeder Pathways Fig 14-9 glycerol Glycerol 3-P  All carbohydrate s enter glycolysis  In muscle, often via hexokinase

32. Case Study A 9-month-old is brought to your clinic with recurrent bouts of sweating and vomiting. Symptoms began shortly after weaning and introduction to solid foods. Testing reveals hypoglycemia and lactic acidosis after consumption of milk formula or fruit. Enzyme activity testing reveals a deficiency in fructose 1-phosphate aldolase. Notably, her 3-year-old brother has a marked aversion to fruit.

33. Fructose intolerance  Hereditary fructose intolerance results from a defect in fructose breakdown in the liver, usually in aldolase.

34. Glycogen Breakdown

35. Glycogen Phosphorylase  Glycogen phoshorylase catalyzes the simultaneous phosphorylation and cleavage of an  -1,4 linked glucose from a non-reducing end of glycogen.  This reaction is called “phosphorolysis.” Glycogen Breakdown

36. Fig 15-12 Pyridoxal phosphate Glycogen Breakdown Step 1. Glycogen Phosphorylase Fig 14-12

37. Fig 15-12 Glycogen Breakdown Phospho- glucomutase Fig 15-29

38.  G6P fate depends on tissue.  In muscle, G6P proceeds through glycolysis.  In liver, G6P is converted to glucose.

39. Limit Dextrins

40. Glycogen Breakdown Debranching enzyme Fig 15-28

41. Glycogen storage diseases

42. Fig 14- 3 Fate of the products, pyruvate and NADH Fig 14- 3

43. Fermentation in Animals

44. Lactic acid from skeletal muscle is sent into the bloodstream. Lactate threshold occurs when production exceeds clearance. Glycolysis cannot continue. Fermentation in Animals

45. Cori Cycle

46. Fermentation in Yeast

48. Pyruvate decarboxylase reaction

51. Alcohol dehydrogenase reaction

52.  Irreversible steps are regulated:  Hexokinase/Glucokinas e  Phosphofructokinase I  Pyruvate Kinase Regulation of glycolysis

53.  Tissue-specific isozymes. Glucose + ATP  G6P + ADP  Feedback inhibition by G6P. Control of Hexokinase

54. Control of PFK-1  Many allosteric effectors; e.g., ATP. H+,H+,

55.  ATP is an allosteric inhibitor of PFK- 1.  Two binding sites: substrate and allosteric site. Control of PFK-1

56. Control of pyruvate kinase PEP + ADP  pyruvate + ATP

57. Fig 15-19 Control of pyruvate kinase

58. Control of glycogen phosphorylase phosphorylase b (inactive) phosphorylase a (active) phosphorylation glycogen breakdown

59.  Glycogen phosphorylase is activated upon phosphorylation by phosphorylase kinase.

60.  Phosphorylase kinase is activated upon phosphorylation by protein kinase A (PKA).  Glycogen phosphorylase is activated upon phosphorylation by phosphorylase kinase.

61.  PKA is activated by cyclic AMP, which is produced by a G-protein in response to epinephrine/glucagon.  Phosphorylase kinase is activated upon phosphorylation by protein kinase A (PKA).  Glycogen phosphorylase is activated upon phosphorylation by phosphorylase kinase.

63. Fig 14-1

64. Transketolase requires thiamine pyrophospate (TPP) as a coenzyme NADPH is necessary to protect against reactive oxygen species Ribose 5-P is necessary in rapidly dividing cells

65. Rxns 1 and 3 produce NADPH Rxn 4 produces ribose-5- phosphate Glucose 6-P + 2 NADP + + H 2 O  Ribose 5-P + 2 NADPH + 2 H + + CO 2 Oxidative phase From C1

66. Key Enzyme: G6P Dehydrogenase

67. Case Study Omar’s mother noticed that every time she served falafel, her son complained of feeling tired, hot, headachy, and sick to his stomach. At first she thought he was just being fussy, but sometimes he would actually look yellow. Medical testing confirmed hemolytic anemia. What’s up with Omar?  A deficiency in G6PDH is the most common human enzyme defect, affecting more than 400 million people worldwide. Protective against malaria. Divicine leads to reactive oxygen species Favism!

68. Case Study Omar’s mother noticed that every time she served falafel, her son complained of feeling tired, hot, headachy, and sick to his stomach. At first she thought he was just being fussy, but sometimes he would actually look yellow. Medical testing confirmed hemolytic anemia. What’s up with Omar? X

69. Regulation  G6P dehydrogenase is allosterically inhibited by NADPH; activated by NADP +

70. Glucose 6-P + 2 NADP + + H 2 O  Ribose 5-P + 2 NADPH + 2 H + + CO 2 Oxidative Phase  Some cells need NADPH but not ribose 5-P  Ribose 5-P can be recycled in the nonoxidative phase

71. Fig 14-22 Fig 14-23 Pentose Phosphate Pathway: Nonoxidative Phase

72. Carbon Shuffling Reactions Glucose 6-phosphate Ribose 5-phosphate Fig 14-23