1. Aerobic Metabolism

2. Summary of Anaerobic Glycolysis Glucose + 2 ADP + 2 P i 2 Lactate + 2 ATP + 2 H 2 O + 2 H +

3. Energetics of Fermentation Glucose ——> 2 Lactate Glucose + 6 O 2 ——> 6 CO 2 + 6 H 2 O ∆G o’ = -200 kJ/mol ∆G o’ = -2866 kJ/mol Most of the energy of glucose is still available following glycolysis!

4. Carbon Atom Oxidation CH 2 —> CH 2 OH —> C=O —> COOH —> CO 2 Glucose Lactate

5. Figure 17-1 Oxidative Fuel Metabolism

6. Oxidation-Reduction Reactions: Electron Transfer Substrate —> NAD + or FAD —> Electron Carriers —> O 2 Electron Transport Oxidative Phosphorylation

7. Figure 17-2 Citric Acid Cycle

8. Electron Transport Oxidative Phosphorylation

10. Summary of Citric Acid Cycle Acetyl-CoA + 3 NAD + + FAD + GDP + P i 2 CO 2 + 3 NADH + 3H + + FADH 2 + GTP + CoA-SH

11. Pyruvate Dehydrogenase: Synthesis of Acetyl-CoA

12. Acetyl-CoA Thioester

13. Sources of Acetyl-CoA Carbohydrates (sugars via glycolysis) Fats (fatty acids) Proteins (amino acids)

14. Pyruvate Dehydrogenase (Formation of Acetyl-SCoA) Oxidative Decarboxylation

15. Pyruvate Dehydrogenase (Multienzyme Complex) E 1 : Pyruvate Dehydrogenase or Pyruvate Decarboxylase E 2 : Dihydrolipoyl Transacetylase E 3 : Dihydrolipoyl Dehydrogenase

16. Multienzyme Complexes Enhanced reaction rates Channeling of reaction intermediates Coordinate regulation

17. Figure 17-3a Electron Micrograph of E. coli Pyruvate Dehydrogenase

18. Organization of E. coli Pyruvate Dehydrogenase Complex

19. Pyruvate Dehydrogenase (Mammalian Enzyme) E 1, E 2, and E 3 E 3 binding protein Kinase (regulation) Phosphatase (regulation)

20. Table 17-1 Coenzymes and Prosthetic Groups of Pyruvate Dehydrogenase

21. Thiamin Pyrophosphate

23. Lipoic Acid

24. Figure 17-7 Reduction of Lipoamide E2E2 E2E2

25. Coenzyme A

26. NAD +

27. Figure 14-12 Flavin Adenine Dinucleotide (FAD)

28. Reduction of FAD

29. Pyruvate Dehydrogenase (Formation of Acetyl-SCoA) Oxidative Decarboxylation

30. Overall Reaction of Pyruvate Dehydrogenase

31. Reaction order of Pyruvate Dehydrogenase

32. Mechanism of Pyruvate Dehydrogenase (Decarboxylation of Pyruvate) Same mechanism as Pyruvate Decarboxylase

34. Page 572 Mechanism of Decarboxylation of Pyruvate

35. Remainder of Reaction

36. Reaction order of Pyruvate Dehydrogenase

37. Mechanism of Pyruvate Dehydrogenase (Hydroxyethyl Group Transfer)

38. Forms of Lipoamide

39. Page 574 Mechanism of Hydroxyethyl Group Transfer

40. Reaction order of Pyruvate Dehydrogenase

41. Mechanism of Pyruvate Dehydrogenase (Transesterification)

42. Page 574 Mechanism of Transesterification

43. Reaction order of Pyruvate Dehydrogenase

44. Mechanism of Pyruvate Dehydrogenase (Reoxidation of Dihydrolipoamide)

45. Mechanism of Pyruvate Dehydrogenase (Oxidation of E 3 –FADH 2 ) E 3 –FADH 2 + NAD + ——> E 3 –FAD + NADH + H +

46. Page 574 Mechanism of Reoxidation of Dihydrolipoamide

47. Page 574 Mechanism of Oxidation of E 3 –FADH 2 Short Lived

48. Page 575 A Swinging Arm Transfers Intermediates E2E2

49. Organization of E. coli Pyruvate Dehydrogenase Complex

50. Pyruvate Dehydrogenase (Formation of Acetyl-SCoA) Oxidative Decarboxylation

51. Regulation of Pyruvate Dehydrogenase Product Inhibition (competitive) –NADH –Acetyl-SCoA Phosphorylation/Dephosphorylation –PDH Kinase: inactivation –PDH Phosphatase: activation

52. Regulation of PDH Kinase (Inactivates PDH by phosphorylation) Activators of PDH Kinase –NADH –Acetyl-SCoA Inhibitors of PDH Kinase –Pyruvate –ADP –Ca 2+ (high Mg 2+ ) –K +

53. Regulation of PDH Phosphatase (Activates PDH by Dephosphorylation) Activators of PDH Pase –Insulin –Mg 2+ –Ca 2+