1. Fundamentals of Biochemistry
Third Edition
Donald Voet • Judith G. Voet • Charlotte W. Pratt
Chapter 17
Citric Acid Cycle
Copyright © 2008 by John Wiley & Sons, Inc.

2. Citric Acid Cycle AKA – Kreb’s Cycle or TCA cycle
Generate 3 NADH, FADH2, GTP, CoA, 2 CO2
Located in mitocondria
Accounts for many intermediates

3. Pyruvate Dehydrogenase Complex
Multienzyme complex
Non-covalently bound
Advantages
Enhanced reaction rates (limited diffusion)
Substrate channeling (limited side reactions)
Coordinated regulation of all steps
Pyruvate dehydrogenase (E1)
Dihydrolipoyl transacetylase (E2)
Dihydrolipoyl dehydrogenase (E3)

4. Dihydolipoyl transacetylase (E2)
Intact PDH E1
24 – E1
24 – E2
12 – E3

7. Reaction 1
Decarboxylation of pyruvate

8. Reaction 2
Hydroxyethyl group transfer

10. Reaction 3
Transesterification

11. Reaction 4
Oxidation of E2 by E3

12. Reaction 5
Oxidation of E3 by FAD

13. Citrate Synthase

14. Aconitase

15. Isocitrate Dehydrogenase

16. α-Ketogluterate Dehydrogenase

17. Succinyl-CoA Synthetase

18. Figure 17-12

19. Succinate Dehydrogenase

20. Fumarase (fumarate hydratase)

21. Malate Dehydrogenase

22. Net energy production

23. Regulation of PDH Product inhibition Covalent modification NADH
Acetyl-CoA
Covalent modification
Phosphorylation
insulin

25. Regulation of TCA Cycle
Substrate availability
Product inhibition
Competitive feedback inhibition

26. Replenishing TCA Cycle