Analogous to Succinate dehydrogenase

1. Analogous to Succinate dehydrogenase

2. Analogous to fumarase

3. Analogous to malate dehydrogenase

4. Claisen cleavage reaction: reverse of citrate synthase

5. Thiolase

7. For a saturated fatty acid with n carbon atoms (even number) -oxidation yields n-2/2 NADH n-2/2 FADH2 You make n/2 Acetyl-CoA, which enter TCA cycle to yield 3n/2 NADH n/2 FADH2 n/2 ATP 2ATP lost in activation

8. What about unsaturated fatty acids?

9. For every double bond that is on a carbon that is an odd number of carbons away from carbonyl: 3 rounds -oxidation Attempt 4th round Doesn’t work

10. Ready for another round of oxidation

11. For every double bond that is on a carbon that is an even number of carbons away from carbonyl: 5 rounds -oxidation Reductase can’t recognize ∆4 unsaturated fatty acids as a substrate

12. Just reduce the double bond Resume oxidation with the cost of 1 NADPH which ultimately costs one NADH

13. What about fatty acids with odd number carbons Last round produces propionyl-CoA instead of Acetyl-CoA

15. For odd chain fatty acids You make n-3/2 Acetyl-CoA and one propionyl-CoA One extra ATP is consumed to convert propionyl-CoA to succinyl-CoA Succinyl-CoA enters TCA cycle This is can be used as an anapleurotic rxn or the succinyl-CoA can be converted to malate. In the latter case.....

16. Conversion of succinyl-CoA to malate makes 1ATP, 1 FADH2

17. Malate Malic enzyme - decarboxylating +1NADPH is converted to NADH pyruvate +1NADH Acetyl-CoA 3NADH + 1FADH2 + ATP

20. So.....for odd chain fatty acids You make n-3/2 Acetyl-CoA and one propionyl-CoA One extra ATP is consumed to convert propionyl-CoA to succinyl-CoA One ATP and one FADH2 are made to convert succinyl-CoA into malate One NADH is made converting malate into Acetyl-CoA 3NADH, 1ATP and 1FADH2 are made oxidizing the Acetyl-CoA Net 1 propionyl-CoA = 2FADH2 + 4NADH + 1ATP

21. In plants the peroxisome is the major site of -oxidation. In animals the peroxisome is mainly responsible for oxidation of very long chain fatty acids. The first step is different because there is no enzyme that can directly inject electrons into the e- transport chain. Instead electrons are put directly onto O2 by an FAD-dependent oxidase. This generates H2O2 which must be degraded by catalase.

22. Ketone Bodies Muscle Liver

24. Other sources of central metabolites?

26. Goin’ Backwards Can you run these pathways in reverse to make glucose?

27. Can the TCA cycle be run in reverse?

28. The Reductive TCA cycle How do you reverse -KGDH? Ketoglutarate synthase 2-oxoglutarate:ferredoxin oxidoreductase Hydrogenase takes electrons from H2 and gives them to ferredoxin which ultimately puts them on -KG.

29. What about isocitrate dehydrogenase? This step can be made reversible if you use a different source of electrons. Use NADPH instead of NADH.

30. Citrate lyase

31. Pyruvate synthase Acetyl-CoA + CO2 ---> pyruvate Pyruvate:ferredoxin oxidoreductase Uses TPP and is essentially the same mechanism Except that the electrons come from H2

32. Malic enzyme decarboxylating The TCA cycle cannot convert Acetyl-CoA into malate. Malate is only part of a pathway to regenerate the catalyst.

33. Pyruvate What if you could skip the decarboxylation steps?

34. Claisen condensation

35. Isocitrate lyase Related to enolase

36. 2Acetyl-CoA + NAD+ + 2H2O ---> succinate + 2CoA + NADH + H+ Succinate enters TCA cycle and is converted to oxaloacetate with the generation of FADH2 and NADH Oxaloacetate is converted to PEP Notice that acetyl-CoA can only be converted to glycolytic intermediates if there is a glyoxalate cycle or a pyruvate synthase

38. Reversing homolactic fermentation This reaction is reversible in liver and muscle ∆G ~ 0

39. What about ethanolic fermentation? Irreversible What about going from acetaldehyde to acetyl-CoA?

40. Aldehyde dehydrogenase: similar to glyceraldehyde DH