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Biochemistry Carbohydrate Metabolism

Citric Acid Cycle (Kreb's Cycle or TCA cycle)

Topic overview

Start with the big picture

The cycle occurs mainly in the mitochondrial matrix, with succinate dehydrogenase embedded in the inner membrane as ETC complex II. Acetyl-CoA combines with oxaloacetate to form citrate. For each acetyl-CoA, the cycle produces 3 NADH, 1 FADH₂, 1 GTP, and 2 CO₂, corresponding to approximately 10 ATP equivalents through oxidative phosphorylation. Isocitrate dehydrogenase is the rate-limiting enzyme; ADP and Ca²⁺ activate it, while ATP and NADH inhibit it. Beyond energy metabolism, cycle intermediates support pathways such as gluconeogenesis, amino acid synthesis, heme production, and fatty acid synthesis. Anaplerotic reactions replenish intermediates, and the cycle depends indirectly on oxygen through electron-carrier regeneration by the ETC.

Learning objectives

What you'll learn

  • Identify the cycle’s location and the distinct membrane role of succinate dehydrogenase.
  • Describe acetyl-CoA entry and the products generated per cycle turn.
  • Explain key regulatory signals affecting isocitrate dehydrogenase and other control points.
  • Recognize the cycle’s biosynthetic roles and how anaplerotic reactions replenish intermediates.
  • Summarize its coenzyme requirements, oxygen dependence, and selected inhibitors.
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