2. METABOLIC BIOCHEMISTRY Summer 2006 Lecture 6 August 18, 2006

3. RECAPITULATION GLYCOGEN BREAKDOWN GLYCOGEN SYNTHESIS

4. Figure 15-4 Pyridoxal phosphate cofactor 1234 1234

5. 1234 1234 1 1234234 Figure 15-4

6. Hydrolysis, NOT Phosphorolysis

7. Figure 15-10 Start with glycogenin, a primer and enzyme. Muscle form and Liver form (glycogenin-2) + UDP-glucose

8. Figure 15-11a INITIATION

9. LNC (3 rd ed) 20-14 (not found in 4 th edition)

10. Figure 15-8 ELONGATION

11. Figure 15-9

12. Figure 15-11b Each molecule has one glycogenin at the reducing end, and many non-reducing ends from which degradation can start

14. CONTROL OF GLYCOGEN SYNTHESIS AND BREAKDOWN

15. Fig 15-13

16. phosphorylasesynthase Phosphofructokinase (PFK-1) Fructose-1,6-bis phosphatase GLYCOGEN UDP-Glu Glu-1P Glu-6P Fru-6P Fru-1,6 bis P DHAP + GAP Four key enzymes controlling the fate of carbohydrate/glucose in our tissues

17. Fig 15-14

18. Fig 15-24

19. Fig 15-26

20. Covalent modifications Ligand-induced conformational changes

22. ATP cAMP adenyl cyclase phosphodiesterase AMP ADP

23. GTP cGMP guanyl cyclase phosphodiesterase

24. LNC 12-15

25. hormone Glycogen ==> Glu-1-P

26. Fig 15-25

27. Fig 15-27

28. Fig 15-29

29. S T U V W HORMONE  ABCDEFABCDEF M N O P Q R E6 E5 E1E2E3E4 Three pathways controlled by a single hormone A signal transduction pathway

31. LNC Chapter 16 The Citric Acid Cycle Krebs Cycle TCA Cycle

35. From G. Perkins, C. Renken, M.E. Martone, S.J. Young, M. Ellisman, and T. Frey

39. Outer membrane Inner membrane Intermembrane space Matrix

40. Pyruvate dehydrogenase as seen by electronmicroscopy E. coli enzyme: Mass > 4.5x10 6 24 copies of trans acetylase (E2) 24 copies of pyruvate dehydrogenase (E1) 12 copies of dihydro- lipoyl dehydrogenase Pyruvate + CoASH + NAD +  acetyl-CoA + CO 2 + NADH

41. E1E1 E3E3 E2E2 The enzyme requires five co-factors: Coenzyme A Thiamine pyrophosphate (TPP) Lipoic acid FAD NAD +

42. LNC 16.3 Coenzyme A

44. LNC 16.14 Lipoamide

45. LNC Fig. 13-18 FAD/FMN FADH 2 /FMNH 2

46. Figure from previous edition of LNC

47. Fig. 16.6

48. TCA CYCLE Krebs cycle Citric acid cycle

49. LNC 16.11 Products from one turn of the Krebs cycle C4 C6 C2 C5 C4 C6

50. LNC 16.8 Citrate Synthase open form without substrates closed from with substrates bound oxaloacetate: yellow acetyl-coA: red

51. LNC 16.9 Iron-sulfur center in aconitase

52. X

53. Stereospecificity of the aconitase reaction with citrate

54. LNC 16.14

55. LNC Fig.16.7 the only membrane- bound enzyme in the TCA cycle

56. LNC Fig.16.18 regulatory molecules: NADH ATP, ADP Ca +2 key allosteric enzymes: the dehydrogenases citrate synthase

57. LNC Fig.16.15 the Krebs cycle is amphibolic

58. THE GLYOXYLATE CYCLE LNC Chapter 16, pages 623-626

59. LNC Fig.16-20 Note that the figure 16-16 in the 3 rd edition has an error (there is an O instead of an H) C6C6 C6C6 C4C4 C4C4 C4C4 C2C2 C2C2 C2C2 from oxidation of fatty acids

61. LNC Fig.16.22

62. End of lecture 6 August 18, 2006