Citric Acid Cycle: A Two Stage Process
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Transcript of Citric Acid Cycle: A Two Stage Process
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Citric Acid Cycle Generates Reductive Equivalents Utilized in Respiration
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Citric Acid Cycle: A Two Stage Process
Stage One: C4 + C2 condensation C6 tricarboxylic acid
Oxidative decarboxylation 2 CO2 Succinyl CoA
Net Result: 2NADH + 2CO2 + Succinyl CoA
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C4 + C2 Condensation ReactionCondensation catalyzed by enzyme dimer Citrate Synthase
RxN Driver
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Citrate Synthase Reaction
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Citrate Synthase Reaction
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Citrate Synthase Reaction
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Citrate Synthase Reaction
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Citrate to Isocitrate Conversion via AconitaseHydroxyl shift for subsequent oxidative decarboxylation
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Isocitrate Dehydrogenase: Oxidation and Decarboxylation
Oxalosuccinate not released from the enzyme
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α-Ketoglutarate Dehydrogenase: Oxidation and Decarboxylation
How similar is α-ketoglutarate dehydrogenase with pyruvate dehydrogenase in terms of substrate components? Reaction mechanism?
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Citric Acid Cycle Part Two: Oxaloacetate Regeneration
Succinyl Coenzyme A Synthetase couples hydrolysis of Coenzyme A (-33 kJ/mol) with GTP formation (-30 kJ/mol)
The energetics works but what about the reaction mechanism?
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Succinyl CoA-Sythetase Generates GTP
What is the Nu:-, E, and leaving group with GTP generation?
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Oxaloacetate Enzyme Regeneration from Succinate• Succinate Dehydrogenase
• Fumerase
• Malate Dehydrogenase
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A Color-Coded Citric Acid Cycle Isocitrate is prochiral
Succinate is a symmetric molecule
Generated products include:
2CO2 + 3NADH + 1FADH2 + GTP + CoA
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Citric Acid Energetics
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Citric Acid Cycle Regulation Points
ATP and NADH are indicators of a high energy state
ADP an indicator of a low energy state
Regulatory sites include:
Isocitrate dehydrogenase
α-Ketoglutarate dehydrogenase
Pyruvate dehydrogenase
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Citric Acid Cycle is a Source for Biosynthetic Precursors
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Transamination Reaction
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Citric Acid Cycle Intermediates:
Replenished as Metabolites are Drawn Off for Biosynthesis
Anapleurotic reactions lead to a replenishment of pathway components (e.g. pyruvate carboxylase).
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Problems: 1, 3, 5, 7 and 9