Theoretical studies on the possible reaction pathway for the deacylation of the AChE-catalyzed reaction

✍ Scribed by Qin Mi Wang; Hua Liang Jiang; Kai Xian Chen; Ru Yun Ji; Yuan-Jie Ye

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 248 KB
• Volume: 74
• Category: Article
• ISSN: 0020-7608
• DOI: 10.1002/(sici)1097-461x(1999)74:3<315::aid-qua4>3.0.co;2-y

✦ Synopsis

Acetylcholinesterase AChE -catalyzed hydrolysis of the Ž . neurotransmitter, acetylcholine ACh , occurs via an acylation and deacylation process. The deacylation process was studied theoretically by the semiempirical quantum chemical method AM1 using the model molecules. To investigate the micro features of the deacylation process, two types of possible reaction mechanisms, the stepwise mechanism and the cooperative mechanism, were proposed and studied. All optimized structures of the model molecules for the possible reactants, intermediates, transition states, and products in the reaction pathway of the two possible mechanisms were obtained. Energy profiles and the structural properties of the transition states indicated that the deacylation process proceeds through the cooperative mechanism, that is, the proton transfer from H O to His440 occurs simultaneously with the nucleophilic attack of the oxygen atom of 2 the H O to the carbonyl carbon of the acylenzyme. Considering the reaction mechanism 2 of acylation, the first process in AChE-catalyzed hydrolysis of ACh, studied in our previous article, we can conclude that both the acylation and deacylation process limit