2.  KG + 3NADPH + NH 3 + 2ATP ---> proline + 3NADP + + 2ADP + 2P i  KG + NADPH + NH 3 + ATP ---> glutamate + NADP + + ADP + P i

3. Proline degradation Proline Pyrroline-5-carboxylate

4. Non-enzymatic

5. Glutamate semialdehyde dehydrogenase Glutamate semialdehyde Glutamate

6. So….Proline = glutamate If: Glu =  -ketoglutarate + NADPH + NH 3 Then: Pro =  -ketoglutarate + NADPH + NH 3 If:  -ketoglutarate = 4 NADH + 2 GTP + 2 FADH 2 + NADPH Then: Pro = 4 NADH +2 GTP + 2 FADH 2 + 2 NADPH + NH 3 If: NADH = 3 ATP GTP = ATP FADH 2 = 2 ATP NH 3 = -2 ATP Then: Pro = 16 ATP + 2 NADPH

8. Arginine Degradation Arginase

9. Ornithine-  -aminotransferase

12. Glutamate semialdehyde dehydrogenase Glutamate semialdehyde Glutamate

13.  KG + Acetyl-CoA + 4NADPH + 3NH 3 + 7ATP + CO 2 ---> arginine + 4NADP + + 6ADP + 1AMP+ 6P i + 1PP i  KG + NADPH + NH 3 + ATP ---> glutamate + NADP + + ADP + P i

14. So…Arg = Glutamate + NADPH + NH 3 If: Glu =  -ketoglutarate + NADPH + NH 3 Then: Arg =  -ketoglutarate + 2 NADPH + 2 NH 3 If:  -ketoglutarate = 4 NADH + 2 GTP + 2 FADH 2 + NADPH Then: Arg = 4 NADH +2 GTP +2 FADH 2 + 3 NADPH + 2NH 3 If: NADH = 3 ATP GTP = ATP FADH 2 = 2 ATP NH 3 = -2 ATP Then: Arg = 14 ATP + 3 NADPH What is the problem with arginine degradation?

15. alpha-ketoglutarate glutamate glutamate semialdehyde prolineN-acetylglutamate semialdehyde arginine Control point

16. oxaloacetate + NADPH + NH 3 + ATP ---> aspartate + NADP + + ADP + P i Remember the cost of aspartate

20. Epimerase

21. oxaloacetate + 4NADPH + 2NH 3 + 3ATP + pyruvate + succinyl-CoA ---> lysine + 4NADP + + 3ADP + 3P i + CO 2

22. This is this is not the only way to make lysine Homocitrate synthase Homoaconitase Homoisocitrate DH  -ketoadipate

23.  -KG + acetyl-CoA + + 2NH 3 + 2NAD + + 4ATP + 4NADPH ---> Lysine + CO 2 + 2NADH + 4NADP + + 4ADP + 4P i

24. Lysine Degradation NADPH

25.  -ketoadipate NAD+

26. FADH2 NADH

28. So…Lysine = NADH +  -ketoadipate + 2 NH 3 If:  -ketoadipate = 2 NADH + FADH 2 + 2 Acetyl-CoA Then: Lys = 3 NADH + FADH 2 + 2 Acetyl-CoA + 2 NH 3 If: Acetyl-CoA = 3 NADH + FADH 2 + GTP Then: Lys = 9 NADH + 3 FADH 2 + 2 GTP + 2 NH 3 If GTP = ATP, NADH = 3 ATP FADH 2 = 2 ATP and NH 3 = -2 ATP Then: Lys = 35 ATP

29. oxaloacetate + 3NADPH + NH 3 + 3ATP ---> threonine + 3NADP + + 3ADP + 3P i

30. gamma lyase/beta synthase

31. Threonine can be degraded in three ways (1) Threonine dehydrogenase pathway Threonine Dehydrogenase

32. Must break C  -C  bond on an amino acid and stabilize a carbanion

33. 2-amino-  -ketobutyrate lyase

34. What happens to the glycine? Glycine Cleavage System: trifunctional enzyme STEP1: decarboxylation of glycine

35. THF N 5,N 10 -methylene-THF STEP 2: formation of N 5,N 10 -methylene-THF

36. NAD + NADH STEP 3: regeneration of catalytic site

37. There is another pathway of glycine degradation From glycine cleavage system Combine the glycine cleavage system with a reverse of the serine hydroxymethyltransferase rxn

38. So…2 glycine = 1 serine + NADH + NH 3

39. If: Ser = pyruvate + NH 3 If: 2 Gly = serine + NADH + NH 3 Then: 2 Gly = 14 ATP, 1 Gly = 7 ATP Then: 2 Gly = pyruvate + NADH + 2 NH 3 If: Pyruvate = 4 NADH + GTP + FADH 2 Then: 2 Gly = 5 NADH + GTP + FADH 2 + 2 NH 3 If: NADH = 3 ATP GTP = ATP FADH 2 = 2 ATP NH 3 = -2 ATP

40. If: glycine is degraded by glycine cleavage system you get 1 N 5,N 10 - methylene tetrahydrofolate, NH 3 and NADH If Acetyl-CoA = 3 NADH + GTP + FADH 2 So… Thr = Gly + Acetyl-CoA + NADH Then: Thr = N 5,N 10 -THF + NH 3 + 2 NADH + Acetyl-CoA Then: Thr = N 5,N 10 -THF + NH 3 + 5 NADH + GTP + FADH 2 If NADH = 3 ATP GTP = ATP FADH 2 = 2 ATP NH 3 = -2 ATP Then: Thr = N 5,N 10 -THF + 16 ATP

41. If: 2 Thr are degraded to 2 Gly If: 1 Gly = N 5,N 10 - THF + 1 NH 3 + 1 NADH by glycine cleavage system Then: 2 Thr = 2 Gly + 2 NADH + 2 Acetyl-CoA And 1 Gly + N 5,N 10 -methylene tetrahydrofolate = serine by serine hydroxymethyltransferase If: Ser = pyruvate + NH 3 Then: 2 Thr = 1 NH 3 + 3 NADH + 2 Acetyl-CoA + serine Then: 2 Thr = 2 NH 3 + 3 NADH + 2 Acetyl-CoA + pyruvate If: Acetyl-CoA = 3 NADH + GTP + FADH 2 Pyruvate = 4 NADH +GTP + FADH 2 Then: 2 Thr = 2 NH 3 + 13 NADH + 3GTP + 3 FADH 2 If: GTP = ATP, NADH = 3 ATP FADH 2 = 2 ATP and NH 3 = -2 ATP Then: 2 Thr = 44 ATP, Thr = 22 ATP

42. (2) Threonine can be degraded by serine hydroxymethyltransferase

43. What happens to acetaldehyde: can’t be put onto THF NAD + NADH Thr = glycine + Acetyl-CoA + NADH Acetaldehyde dehydrogenase

44. If: glycine is degraded by glycine cleavage system you get 1 N 5,N 10 - methylene tetrahydrofolate, NH 3 and NADH If Acetyl-CoA = 3 NADH + GTP + FADH 2 Thus: Thr = Gly + Acetyl-CoA + NADH Then: Thr = N 5,N 10 -THF + NH 3 + 2NADH + Acetyl-CoA Then: Thr = N 5,N 10 -THF + NH 3 + 5 NADH + GTP + FADH 2 If NADH = 3 ATP GTP = ATP FADH 2 = 2 ATP NH 3 = -2 ATP Then: Thr = N 5,N 10 -THF + 16 ATP

45. (3) Threonine can be converted to  -ketobutyrate by threonine (serine) dehydratase

47. What happens to  -ketobutyrate?  -ketobutyrate dehydrogenase Same mechanism as pyruvate dehydrogenase and  -ketoglutarate dehydrogenase.

48. Thr = propionyl-CoA + NADH NAD + NADH

49. What happens to propionyl-CoA?: Propionyl-CoA carboxylase Loss of ATP!

50. Methylmalonyl-CoA epimerase: Why?

51. Stability order of radicals allylic > R 3 C > R 2 CH > RCH 2 > CH 3 > vinylic

53. So… Thr = succinyl-CoA - ATP + NADH If: Succinyl-CoA = malate + GTP + FADH 2 Then: Thr = malate + GTP - ATP + NADH + FADH 2 If: Malate = pyruvate + NADPH - NADH If: Pyruvate ---> 4 NADH + GTP + FADH 2 Then: Thr = FADH 2 + pyruvate + NADPH Then: Thr = 4NADH + GTP + 2 FADH 2 + NADPH If GTP = ATP, NADH = 3 ATP FADH 2 = 2 ATP and NH 3 = -2 ATP Then: Thr = 17 ATP + NADPH If: GTP = ATP Then: Thr = malate + NADH + FADH 2

54. Degradation of glycine by this pathway makes 1 N 5,N 10 - methylene tetrahydrofolate, NH 3 and NADH If: NADH is 3 ATP but NH 3 is -2 ATP Then: Gly = 1 ATP + 1 N 5,N 10 -THF

56. Asp semialdehyde lysinethreonine/methionine

57. homoserine O-succinylhomoserine O-phosphohomoserine methionine threonine

58. oxaloacetate + 3NADPH + 2ATP + succinyl-CoA + cysteine + N 5 -methyl-THF ---> methionine + succinate + pyruvate + 3NADP + + 2ADP + 2P i N 5 -methyl-THF comes from serine ---> glycine + N 5,N 10 -methylene THF N 5,N 10 -methylene THF + NADH ---> N 5 -methyl THF + NAD +

61. 2 ways to degrade serine. (1) Serine dehydratase breaks the C  -C  bond

62. Serine is converted to pyruvate + NH 3 at no cost

63. If: Pyruvate = 4 NADH + 1 FADH 2 + GTP Then: Ser = 13 ATP So: Ser = pyruvate + NH 3 Then: Ser = 4 NADH + FADH 2 + GTP + NH 3 If: NADH = 3 ATP GTP = ATP FADH 2 = 2 ATP NH 3 = -2 ATP

64. (2) Serine hydroxymethyltransferase: bifunctional enzyme STEP 1: formation of glycine

65. What happens to formaldehyde? STEP 2: formation of N 5,N 10 -methylene-THF Serine hydroxymethyl transferase can be run in reverse to make serine from glycine and N 5,N 10 -methylene THF

66. 3-phosphoglycerate + NAD + + NADPH + NH 4 + + ATP ---> Serine + NADH + NADP + + ADP + 2P i 3-phosphoglycerate + NAD + + NADPH + NH 4 + + ATP + THF ---> glycine + NADH + NADP + + ADP + 2P i + N 5,N 10 -methylene THF CO 2 + NH 4 + + N 5,N 10 -methylene THF + NADH ---> Glycine + THF + NAD + Reverse the glycine cleavage system

67. What happens to glycine? Glycine Cleavage System: trifunctional enzyme STEP1: decarboxylation of glycine

68. THF N 5,N 10 -methylene-THF STEP 2: formation of N 5,N 10 -methylene-THF

69. So…degradation of serine with serine hydroxymethyltransferase followed by the glycine cleavage system makes 2 N 5,N 10 - methylene-THF, NH 3 and NADH NAD + NADH If: NADH is 3 ATP but NH 3 is -2 ATP Then: Ser = 1 ATP + 2 N 5,N 10 -THF STEP 3: regeneration of catalytic site

70. Degradation of glycine by this pathway makes 1 N 5,N 10 - methylene tetrahydrofolate, NH 3 and NADH If: NADH is 3 ATP but NH 3 is -2 ATP Then: Gly = 1 ATP + 1 N 5,N 10 -THF

71. There is another pathway of glycine degradation From glycine cleavage system Combine the glycine cleavage system with a reverse of the serine hydroxymethyltransferase rxn

72. So…2 glycine = 1 serine + NADH + NH 3

73. If: Ser = pyruvate + NH 3 If: 2 Gly = serine + NADH + NH 3 Then: 2 Gly = 14 ATP, 1 Gly = 7 ATP Then: 2 Gly = pyruvate + NADH + 2 NH 3 If: Pyruvate = 4 NADH + GTP + FADH 2 Then: 2 Gly = 5 NADH + GTP + FADH 2 + 2 NH 3 If: NADH = 3 ATP GTP = ATP FADH 2 = 2 ATP NH 3 = -2 ATP

76. Pyruvate + NH 3 + ATP + NADPH ---> alanine + ADP + P i + NADP +