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SURVEY OF BIOCHEMISTRY Citric Acid Cycle

SURVEY OF BIOCHEMISTRY Citric Acid Cycle. PRS. Which substrates in the TCA cycle are coupled to the production of CO 2 ? Isocitrate and alpha-ketoglutarate Citrate and alpha-ketoglutarate Oxaloacetate and citrate Succinate and malate. PRS Answer. Isocitrate and Alpha-ketoglutarate. PRS.

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SURVEY OF BIOCHEMISTRY Citric Acid Cycle

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  1. SURVEY OF BIOCHEMISTRYCitric Acid Cycle

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

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

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

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

  10. + Pyruvate DehydrogenaseE1 Cleaves off CO2

  11. Pyruvate DehydrogenaseE2 Catalyzes Acetyl-CoA Formation

  12. Pyruvate DehydrogenaseE2 Catalyzes Acetyl-CoA Formation Acetyl-CoA is formed, but the oxidized form of the lipoic acid cofactor must beregenerated.

  13. Pyruvate DehydrogenaseE3 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 DehydrogenaseE3 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 inhibitionwould you expect malonate to work?

  23. Fumarase

  24. Malate Dehydrogenase +

  25. Malate Dehydrogenase

  26. Regulation of the TCA CycleExcess Products Prohibit entry by buildingexcess Acetyl-CoA and NADH Deactivate pyruvate dehydrogenase

  27. Regulation of the TCA CycleInactivate Pyruvate Dehydrogenase

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

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

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