SURVEY OF BIOCHEMISTRY Citric Acid Cycle

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SURVEY OF BIOCHEMISTRYCitric Acid Cycle
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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

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PRS Answer
Isocitrate and Alpha-ketoglutarate
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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

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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

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PRS

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

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PRS

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

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TCA Cycle Overview
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Pyruvate Dehydrogenase

• Multienzyme complex E1, E2, E3
• Oxidative decarboxylation
• Requires 5 cofactors
• CoA
• NAD
• FAD
• Lipoic Acid
• Thiamine Pyrophosphate

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Pyruvate DehydrogenaseE1 Cleaves off CO2
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Pyruvate DehydrogenaseE2 Catalyzes Acetyl-CoA
Formation
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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.
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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?
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Pyruvate DehydrogenaseE3 Produces NADH
Now the oxidized form of E3 needs to be
regenerated. How does this happen?
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Citrate Synthase
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Aconitase
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Isocitrate Dehydrogenase
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Alpha-Ketoglutarate Dehydrogenase
Notice the similarities between this reaction and
that of pyruvate dehydrogenase.
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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.
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Succinyl-CoA Synthetase
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Succinate Dehydrogenase
Rxn is strongly inhibited by malonate
By what mode of inhibitionwould you expect
malonate to work?
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Fumarase
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Malate Dehydrogenase

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Malate Dehydrogenase
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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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Regulation of the TCA CycleInactivate Pyruvate
Dehydrogenase
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Controlling Enzymes in the TCA Cycle
Citrate Synthase Isocitrate Dehydrogenase Alpha-
Ketoglutarate Dehydrogenase
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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