TCA

• 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


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


  Transient one with very short half-life, immediately converted to Isocitrate
• Isocitrate to α-ketoglutarate


  1. Isocitrate oxalosuccinate -ketoglutarate

  2. Oxidative decarboxylation

  3. Oxalosuccinate is unstable so it undergoes spontaneous decarboxylation
• TCA Cycle


  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
• Amphibolic nature of TCA cycle

  • Supplies intermediates for synthesis of non-essential amino acids, purines, pyrimidines, fatty acids, steroids
  • Oxaloacetate, citrate, α-KG, succinyl CoA are key intermediates
• Anaplerosis

  1. Reactions to replenish intermediates of TCA cycle

  2. Pyruvate + CO2 + ATP oxaloacetate

  3. Pyruvate + CO2 + NADPH + H+ malate
• Inhibitors of TCA cycle enzymes: fluoroacetate, arsenite, malonate
• Regulation of TCA cycle

  • Citrate synthase inhibited by ATP, NADH, acyl CoA, succinyl CoA
  • Isocitrate dehydrogenase inhibited by ATP, NADH, activated by ADP
  • α-KG dehydrogenase inhibited by NADH, succinyl CoA
  • Availability of ADP is important for proceeding the cycle, if not oxidation of NADH and FADH2 through electron transport chain stops