Biochemistry · MU Sofia

18. Citric Acid Cycle

Explains the citric acid cycle as a hub linking carbohydrate, fat and protein metabolism, covering its role in catabolism and anabolism and where acetyl-CoA comes from. It walks through the enzymes and steps, the net yield per acetyl-CoA, and regulation, with isocitrate dehydrogenase named as the rate-limiting step. It also covers anaplerotic reactions and pyruvate dehydrogenase deficiency, and ends with four multiple-choice questions and answers.

Inside: 13 sections · 6 labelled pictures · 10 flashcards · 4 min

Topic 18 of 70 in the MU Sofia syllabus for Biochemistry (Medicine, Year 2). The free AceMed note covers it in 11 sections, about 540 words (4 min of reading), with 10 flashcards.

In this note

  1. Citric Acid Cycle – Importance for Catabolism and Anabolism
  2. Importance in Catabolism
  3. Importance in Anabolism
  4. Chemical Reactions in the Citric Acid Cycle
  5. Metabolic and Energy Balance
  6. Mechanisms of Regulation
  7. The Rate Limiting Step!!
  8. Anaplerotic Reactions
  9. Pyruvate Dehydrogenase Deficiency
  10. MCQs
  11. Answers

Citric Acid Cycle – Importance for Catabolism and Anabolism

Central Metabolic Pathway: The CAC, also known as the Krebs cycle or tricarboxylic acid (TCA) cycle, is a key metabolic pathway that connects carbohydrate, fat, and protein metabolism. It is pivotal in the aerobic production of energy.

Importance in Catabolism

  • Energy Production: The cycle oxidizes acetyl-CoA, releasing CO₂ and transferring energy to generate ATP indirectly through electron carriers (NADH, FADH₂).
  • Breakdown of Metabolic Fuels: Acetyl-CoA, which enters the CAC, can be derived from carbohydrates via glycolysis, from fatty acids via β-oxidation, and from some amino acids.

Importance in Anabolism

  • Precursor Supply: Provides key intermediates for biosynthesis of various compounds:
  • Oxaloacetate: For gluconeogenesis.
  • α-Ketoglutarate and Oxaloacetate: For amino acid synthesis.
  • Citrate: Exported to cytosol for fatty acid and cholesterol synthesis.
  • Flexibility in Function: While predominantly catabolic, it facilitates anabolic reactions by providing necessary intermediates.

Chemical Reactions in the Citric Acid Cycle

1. Conversion Steps and Key Enzymes

  • Acetyl-CoA + Oxaloacetate → Citrate: Catalyzed by citrate synthase.
  • Citrate Isomerization to Isocitrate: Via aconitase.
  • Oxidative Decarboxylations: Conversion of isocitrate through α-ketoglutarate to succinyl-CoA, generating NADH, catalyzed by isocitrate dehydrogenase and α-ketoglutarate dehydrogenase.
  • Substrate-Level Phosphorylation: Succinyl-CoA to succinate, producing GTP or ATP, via succinyl-CoA synthetase.
  • Oxidation and Regeneration of Oxaloacetate: Via succinate dehydrogenase and fumarase, ending with malate dehydrogenase.

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