Which amino acids are involved in the degradation of acetylcholine?

• A. Serine 200 and Histidine 440
• B. Tryptophan and Asparagine 617
• C. Aspartic acid 311 and Serine 200
• D. Histidine 440 and Aspartic acid 311

Answer: (A)

The key concept is how acetylcholinesterase breaks down acetylcholine at the synapse. This enzyme uses a catalytic trio to enable hydrolysis, with serine acting as the nucleophile, histidine serving as a base to activate serine, and a nearby acidic residue stabilizing histidine. In acetylcholinesterase, Serine 200 and Histidine 440 form the essential pair that drives the reaction: Serine 200 attacks the acetylcholine carbonyl carbon to form an acetyl-enzyme intermediate, activated by Histidine 440, which shuttles protons during catalysis. A third residue (glutamate) stabilizes Histidine, completing the triad that enables efficient breakdown of acetylcholine into choline and acetate. Therefore, Serine 200 and Histidine 440 are the amino acids involved in the degradation of acetylcholine.