1 survey of biochemistry citric acid cycle. 2 prs which substrates in the tca cycle are coupled to...
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2
PRS
• Which substrates in the TCA cycle are coupled to the production of CO2?
1. Isocitrate and alpha-ketoglutarate2. Citrate and alpha-ketoglutarate3. Oxaloacetate and citrate4. Succinate and malate
4
PRS
• In the net TCA cycle rxn, what are the products?
1. 3 NADH + FAD + GDP + 2CO2 + CoA
2. 3 NADH + FAD + GTP + 2CO2 + CoA
3. 3 NAD+ + FADH2 + GTP + 2CO2 + Acetyl-CoA
4. 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
7
PRS
• Which enzyme catalyzes the reversible isomerization of citrate and isocitrate?
1. Citrate synthase2. Aconitase3. Triose Phosphate Isomerase4. Isocitrate Dehydrogenase
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TCA Cycle Overview
Pyruvate Acetyl CoA
Oxaloacetate Citrate
Isocitrate
Alpha-Ketoglutarate
Succinyl-CoASuccinate
Fumarate
L-Malate3 NAD+ + FAD + GDP + Pi + Acetyl-CoA
3NADH + FADH2 + GTP + 2 CO2
CO2
NAD+ NADH
9
Pyruvate Dehydrogenase
• Multienzyme complex: E1, E2, E3
• Oxidative decarboxylation• Requires 5 cofactors
– CoA– NAD+
– FAD– Lipoic Acid– Thiamine Pyrophosphate
Pyruvate Acetyl CoA
CO2
NAD+ NADH
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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?
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.
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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.
22
Succinate Dehydrogenase
Rxn is strongly inhibited by malonate
By what mode of inhibitionwould you expect malonate
to work?
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Regulation of the TCA CycleExcess Products
1. Prohibit entry by buildingexcess Acetyl-CoA and NADH
2. Deactivate pyruvate dehydrogenase
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Controlling Enzymes in the TCA Cycle
Citrate Synthase
Isocitrate Dehydrogenase
Alpha-Ketoglutarate Dehydrogenase
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