Citric Acid Cycle: Step 1

Key Points

• High-Energy Thioester Bond: The cleavage of the high-energy thioester bond between sulfur and carbon is crucial.
• Role of Histidine 274 (His 274): Acts as an H+ ion donor:
  • Initially, His 274 donates an H ion to promote hydrolysis.
  • In the final step, His 274 donates an H ion to the oxygen of the carbonyl group.
• Hydrolysis Process:
  • Water molecule cleaves the thioester bond.
  • His 274 promotes the hydrolysis of the citryl-CoA complex.
• Formation and Stability:
  • The citryl-CoA complex is stabilized via interactions in a specific region.
  • Hydrolysis of citryl-CoA results in the formation of citrate and release of coenzyme A.

Summary

• Final Step: Involves His 274 acting as an H+ donor to stimulate the hydrolysis of the citryl-CoA, forming citrate and releasing coenzyme A.
• Outcome: Step 1 of the citric acid cycle leads to the formation of citrate, with His 274 playing a crucial role in the hydrolysis mechanism.