TCA Cycle 24

• Tricarboxylic acid cycle (TCA Cycle)


  Also known as Kreb's cycle or Citric acid cycle
• TCA Cycle


  • Is the final common oxidative pathway for carbohydrates, fats and amino acids
  • Along with energy, cycle supplies many intermediates required for the synthesis of amino acids, glucose, heme etc.
  • Site: mitochondrial matrix
  • Oxidation of acetyl CoA to CO2 and H2O
  • Occurs in a cyclic manner, generates ATP
• TCA Cycle


  Carbon, acetyl CoA + 4 carbon, Oxaloacetate = 6 carbon tricarboxylic acid, citrate
• Cis-aconitate


  Transient one with very short half-life, immediate H2O added to it and forms Isocitrate
• Isocitrate to α-ketoglutarate


  1. Isocitrate oxalosuccinate -ketoglutatrate

  2. Oxalosuccinate is unstable so it undergoes spontaneous decarboxylation to form α-KG
• TCA Cycle


  Is both catabolic and anabolic - amphibolic
• Steps 4, 6, 10 of TCA Cycle produce 3 NADH
• 1 NADH = 3 ATP
• Step 8 of TCA Cycle produces 1 FADH2
• 1 FADH2 = 2 ATP
• Step 7 of TCA Cycle produces 1 GTP
• 1 GTP = 1 ATP
• TCA Cycle


  • Is amphibolic - both catabolic and anabolic
• Products of TCA Cycle

  • Non essential amino acids
  • Aspartate
  • Acetyl CoA
  • Purines
  • Pyrimidines
  • Oxaloacetate
  • Citrate
  • Acetyl CoA
  • Fatty acids
  • Steroids
  • Pyruvate
  • Malate
  • α-KG
  • Succinyl CoA
  • Glutamate
  • Heme
• Anaplerosis


  The reactions concerned to replenish the intermediates of TCA cycle
• Anaplerotic reactions


  1. Pyruvate +CO2 + ATP carboxylase oxaloacetate + ADP + Pi

  2. Pyruvate +CO2 + NADPH + H + Malic enzyme Malate
• Inhibitors of TCA Cycle enzymes

  • Aconitase - fluoroacetate
  • α-Ketoglutarate DH - Arsenite (non-competitive)
  • Succinate DH - Malonate (competitive)
• Regulation of TCA Cycle

  • Citrate synthase: inhibited by ATP, NADH, acyl CoA and succinyl CoA
  • Isocitrate dehydrogenase: Inhibited by ATP and NADH, activated by ADP
  • α-KG dehydrogenase inhibited by NADH & succinyl CoA
  • Availability of ADP is important for proceeding the TCA cycle