Citric Acid Cycle: Steps 5 to 8

Step 5: Conversion of Succinyl-CoA to Succinate

• Reactant: Succinyl-CoA
• Product: Succinate, GTP, and Coenzyme A
• Enzyme: Succinyl-CoA Synthetase
• Key Point: This is the only step where a high-energy GTP molecule is generated.
• Process:
  • Cleavage of the high-energy thioester bond in Succinyl-CoA releases energy.
  • This energy is used to attach a phosphate group to GDP, forming GTP.
  • Releases Coenzyme A and forms the four-carbon succinate molecule.
  • GTP can be used in G-protein-related processes or converted to ATP via nucleotide diphosphokinase.
• Detailed Mechanism:
  • Inorganic orthophosphate attacks the carbonyl carbon in Succinyl-CoA, releasing Coenzyme A and forming a succinyl-phosphate intermediate.
  • This intermediate is then attacked by a catalytic histidine residue, forming phosphohistidine and releasing succinate.
  • Phosphohistidine transfers the phosphate group to GDP, forming GTP.

Step 6: Conversion of Succinate to Fumarate

• Reactant: Succinate
• Product: Fumarate
• Enzyme: Succinate Dehydrogenase
• Key Point: This step is an oxidation-reduction reaction.
• Process:
  • Dehydrogenation of succinate removes two hydrogen atoms, forming fumarate.
  • The two hydrogen atoms are transferred to FAD, forming FADH2.
  • Succinate dehydrogenase is part of the inner mitochondrial membrane and the electron transport chain.
  • FADH2 donates electrons to the electron transport chain, aiding in ATP generation.

Step 7: Conversion of Fumarate to Malate

• Reactant: Fumarate
• Product: Malate
• Enzyme: Fumarase
• Key Point: This is a hydration reaction.
• Process:
  • Addition of water to fumarate.
  • Forms the L-isomer of malate.

Step 8: Conversion of Malate to Oxaloacetate

• Reactant: Malate
• Product: Oxaloacetate
• Enzyme: Malate Dehydrogenase
• Key Point: This step regenerates oxaloacetate to continue the cycle.
• Process:
  • Oxidation of malate.
  • NAD+ is reduced to NADH in the process by accepting a hydride ion.
  • This step is endergonic and is driven forward by coupling with other exergonic processes in the cycle and the electron transport chain.

Linking Steps

• Substrate-Level Phosphorylation: GTP generation in Step 5 is an example of substrate-level phosphorylation.
• Oxidative Phosphorylation Link: Generation of FADH2 in Step 6 links citric acid cycle to oxidative phosphorylation.

Summary

• The citric acid cycle is a sequence of enzymatic reactions that fully oxidize acetyl-CoA to CO2, with the production of high-energy intermediates.
• Each step is precisely controlled and has a specific role in energy metabolism and the overall production of ATP.