1. SURVEY OF BIOCHEMISTRY Citric Acid Cycle

2. Isocitrate and alpha-ketoglutarate Citrate and alpha-ketoglutarate
PRS
Which substrates in the TCA cycle are coupled to the production of CO2?
Isocitrate and alpha-ketoglutarate
Citrate and alpha-ketoglutarate
Oxaloacetate and citrate
Succinate and malate

3. PRS Answer
Isocitrate
and
Alpha-ketoglutarate

4. In the net TCA cycle rxn, what are the products?
PRS
In the net TCA cycle rxn, what are the products?
3 NADH + FAD + GDP + 2CO2 + CoA
3 NADH + FAD + GTP + 2CO2 + CoA
3 NAD+ + FADH2 + GTP + 2CO2 + Acetyl-CoA
3 NADH + FADH2 + GTP + 2CO2 + CoA

5. In the net TCA cycle rxn, what are the products?
PRS - Answer
In the net TCA cycle rxn, what are the products?
3 NADH + FAD + GDP + 2CO2 + CoA
3 NADH + FAD + GTP + 2CO2 + CoA
3 NAD+ + FADH2 + GTP + 2CO2 + Acetyl-CoA
3 NADH + FADH2 + GTP + 2CO2 + CoA

6. In what form does carbon enter the TCA cycle?
PRS
In what form does carbon enter the TCA cycle?
Pyruvate
Glucose
CO2
Acetyl CoA

7. Triose Phosphate Isomerase Isocitrate Dehydrogenase
PRS
Which enzyme catalyzes the reversible isomerization of citrate and isocitrate?
Citrate synthase
Aconitase
Triose Phosphate Isomerase
Isocitrate Dehydrogenase

8. TCA Cycle Overview Pyruvate Acetyl CoA Oxaloacetate Citrate L-Malate
NAD+
NADH
Pyruvate
Acetyl CoA
Oxaloacetate
Citrate
L-Malate
Isocitrate
3 NAD+ + FAD + GDP + Pi + Acetyl-CoA
3NADH + FADH2 + GTP + 2 CO2
Alpha- Ketoglutarate
Fumarate
Succinyl-CoA
Succinate

9. Pyruvate Dehydrogenase
CO2
NAD+
NADH
Pyruvate
Acetyl CoA
Multienzyme complex: E1, E2, E3
Oxidative decarboxylation
Requires 5 cofactors
CoA
NAD+
FAD
Lipoic Acid
Thiamine Pyrophosphate

10. Pyruvate Dehydrogenase E1 Cleaves off CO2+

11. Pyruvate Dehydrogenase E2 Catalyzes Acetyl-CoA Formation

12. Pyruvate Dehydrogenase E2 Catalyzes Acetyl-CoA Formation
Acetyl-CoA is formed, but the oxidized form of the lipoic acid cofactor must be regenerated.

13. Pyruvate Dehydrogenase E3 Regenerates the Disulfide
Notice the redox chemistry here:
The lipoic acid group of E2 has been regenerated.
Now the oxidized form of E3 needs to be regenerated. How does this happen?

14. Pyruvate Dehydrogenase E3 Produces NADH
Now the oxidized form of E3 needs to be regenerated. How does this happen?

15. Citrate Synthase

16. Aconitase

17. Isocitrate Dehydrogenase

18. Alpha-Ketoglutarate Dehydrogenase
Notice the similarities between this reaction and that of pyruvate dehydrogenase.

19. Alpha-Ketoglutarate Dehydrogenase
Notice the similarities between this reaction and that of pyruvate dehydrogenase.
Both Pyruvate and alpha-ketoglutarate are alpha-keto acids.

20. Alpha-Ketoglutarate Dehydrogenase
Notice the similarities between this reaction and that of the pyruvate dehydrogenase complex.
Both rxns produce CO2 and NADH and H+. Both rxns use CoA as a cofactor.

21. Succinyl-CoA Synthetase

22. Succinate Dehydrogenase
Rxn is strongly inhibited by malonate
By what mode of inhibition would you expect malonate to work?

23. Fumarase

24. Malate Dehydrogenase +

25. Malate Dehydrogenase

26. Regulation of the TCA Cycle Excess Products
Prohibit entry by building excess Acetyl-CoA and NADH
Deactivate pyruvate dehydrogenase

27. Regulation of the TCA Cycle Inactivate Pyruvate Dehydrogenase

28. Controlling Enzymes in the TCA Cycle
Citrate Synthase
Isocitrate Dehydrogenase
Alpha-Ketoglutarate Dehydrogenase

29. Wed: Cover Ch. 18 Thur: Exam #3 Coming Up Chapter 15: Glycolysis
Chapter 16: Glycogen Metabolism
Chapter 17: TCA Cycle
Chapter 18: Electron Transport and Oxidative Phosphorylation