SURVEY OF BIOCHEMISTRY Citric Acid Cycle

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

PRS Answer Isocitrate and Alpha-ketoglutarate

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

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

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

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

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

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

Pyruvate Dehydrogenase E1 Cleaves off CO2 +

Pyruvate Dehydrogenase E2 Catalyzes Acetyl-CoA Formation

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

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?

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

Citrate Synthase

Aconitase

Isocitrate Dehydrogenase

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

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

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.

Succinyl-CoA Synthetase

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

Fumarase

Malate Dehydrogenase +

Malate Dehydrogenase

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

Regulation of the TCA Cycle Inactivate Pyruvate Dehydrogenase

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

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