survey of biochemistry citric acid cycle
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
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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?
1. Isocitrate and alpha-ketoglutarate2. Citrate and alpha-ketoglutarate3. Oxaloacetate and citrate4. 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?
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
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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?
1.Pyruvate2.Glucose3.CO2
4.Acetyl CoA
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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
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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 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