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Questions and Answers
What is another name for the citric acid cycle?
Krebs cycle
What is the primary substrate of the citric acid cycle?
The citric acid cycle is involved only in catabolic processes.
False
Which of the following compounds inhibits citrate synthase?
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What enzyme catalyzes the isomerization of citrate to isocitrate?
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During which reaction is the first release of CO2 in the citric acid cycle produced?
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What is produced during the cleavage of succinyl CoA?
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Fumarase catalyzes the hydration of fumarate to L-malate.
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Which coenzyme is required for the oxidation of malate to oxaloacetate?
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Study Notes
Overview of the Citric Acid Cycle
- Also known as Krebs cycle or tricarboxylic acid (TCA) cycle.
- Comprises a series of enzymatically catalyzed reactions for oxidizing metabolic fuels: carbohydrates, fatty acids, ketone bodies, and amino acids.
- Central function is to oxidize acetyl CoA into carbon dioxide (CO2) and water (H2O).
- Major site for oxygen consumption and ATP production in most animals, including humans.
Functions of the TCA Cycle
- Amphibolic pathway: Functions in both anabolic and catabolic processes.
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Anabolic reactions:
- Intermediates serve as precursors for glucose synthesis from amino acids.
- Provides building blocks for heme synthesis.
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Catabolic reactions:
- Degrades two-carbon acetyl residues from carbohydrates, fatty acids, and amino acids.
Key Reactions in the Citric Acid Cycle
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Citrate Synthesis:
- Catalyzed by citrate synthase from acetyl CoA and oxaloacetate.
- Inhibited by ATP, NADH, succinyl CoA, and fatty acyl CoA.
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Role of Citrate:
- Serves as an intermediate and source of acetyl CoA for lipid synthesis.
- Inhibits phosphofructokinase-I, affecting glycolysis.
- Activates acetyl CoA carboxylase for fatty acid synthesis.
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Isomerization of Citrate:
- Converts citrate to isocitrate via aconitase (iron-sulphur center).
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Oxidation and Decarboxylation of Isocitrate:
- Isocitrate dehydrogenase converts isocitrate to α-ketoglutarate.
- Produces first three NADH and releases first CO2.
- Activated by ADP, inhibited by ATP and NADH.
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Conversion of α-Ketoglutarate to Succinyl CoA:
- Catalyzed by α-ketoglutarate dehydrogenase complex.
- Produces second NADH and releases second CO2.
- Reaction equilibrium favors succinyl CoA, a high-energy thioester.
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Cleavage of Succinyl CoA to Succinate:
- Catalyzed by succinate thiokinase, releases succinate and CoA.
- Produces GTP from GDP through substrate-level phosphorylation.
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Oxidation of Succinate to Fumarate:
- Catalyzed by succinate dehydrogenase, requires FAD as a cofactor.
- Inhibited by malonate (structural analogue) and oxaloacetate.
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Hydration of Fumarate to L-Malate:
- Catalyzed by fumarase, a reversible reaction.
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Oxidation of Malate to Oxaloacetate:
- Malate dehydrogenase catalyzes conversion, requiring NAD+ as a coenzyme.
- Represents third step of NADH production, contributing to ATP generation through the electron transport chain.
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