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Citric Acid Cycle (Steps 2-4)

May 20, 2024

Citric Acid Cycle (Steps 2-4)

Overview

  • Focus on steps 2, 3, and 4 of the Citric Acid Cycle
  • Step 1: Formation of citrate from acetyl group and oxaloacetate
  • Steps 2-4: Preparation and decarboxylation of citrate to extract energy

Step 2: Isomerization of Citrate

  • Objective: Prepare citrate for oxidative decarboxylation (steps 3 and 4)
  • Process: Conversion of citrate to isocitrate
    • Citrate and isocitrate are isomers
    • Difference: Position of hydroxyl group
  • Mechanism
    1. Dehydration: Removal of hydroxyl group and H⁺ to form cis-aconitate
    2. Hydration: Addition of H₂O to cis-aconitate to form isocitrate
  • Enzyme: Aconitase (contains iron-sulfur complex 4Fe-4S)
    • Catalyzes dehydration and hydration reactions
    • Acts by holding citrate within active site

Step 3: Oxidative Decarboxylation of Isocitrate

  • Objective: Produce NADH and CO₂
  • Process: Two-step conversion of isocitrate to alpha-ketoglutarate
    1. Oxidation: Isocitrate reacts with NAD⁺ to form NADH and oxalosuccinate
    2. Decarboxylation: Oxalosuccinate transforms to alpha-ketoglutarate
  • Enzyme: Isocitrate dehydrogenase
    • Reduces NAD⁺ to NADH
    • Catalyzes formation of unstable oxalosuccinate
    • Oxalosuccinate is a beta-keto acid (unstable)
    • High-energy electrons abstracted for use in electron transport chain (ETC)
  • Net Reaction
    • Reactants: Isocitrate, NAD⁺
    • Products: NADH, CO₂, alpha-ketoglutarate

Step 4: Oxidative Decarboxylation of Alpha-Ketoglutarate

  • Objective: Produce another NADH and CO₂, form succinyl-CoA
  • Process: Conversion of alpha-ketoglutarate to succinyl-CoA
    • Requires coenzyme A (CoA)
    • Formation of high-energy thioester bond in succinyl-CoA
  • Enzyme: Alpha-ketoglutarate dehydrogenase complex
    • Similar to enzyme complex in pyruvate decarboxylation
    • Consists of three types of enzymes
      1. E1: Alpha-ketoglutarate dehydrogenase (uses TPP cofactor)
      2. E2: Dihydrolipoyl succinyltransferase (uses lipoic acid derivative)
      3. E3: Dihydrolipoyl dehydrogenase (uses FAD cofactor)
  • Net Reaction
    • Reactants: Alpha-ketoglutarate, NAD⁺, CoA
    • Products: NADH, CO₂, succinyl-CoA
    • High-energy electrons will be used in ETC

Conclusion

  • Steps 2, 3, and 4 crucial for preparing and extracting energy from citrate cycle intermediates
  • Each step involves specific enzymes and cofactors to catalyze reactions
  • Produced NADH and energy intermediates will play a role in ATP synthesis through ETC

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