Fundamental reaction pathway and free energy profile for butyrylcholinesterase-catalyzed hydrolysis of heroin.

ABSTRACT: The pharmacological function of heroin requires an activation process that transforms heroin into 6-monoacetylmorphine (6-MAM), which is the most active form. The primary enzyme responsible for this activation process in human plasma is butyrylcholinesterase (BChE). The detailed reaction pathway of the activation process via BChE-catalyzed hydrolysis has been explored computationally, for the first time, in this study via molecular dynamics simulation and first-principles quantum mechanical/molecular mechanical free energy calculations. It has been demonstrated that the whole reaction process includes acylation and deacylation stages. The acylation consists of two reaction steps, i.e., the nucleophilic attack on the carbonyl carbon of the 3-acetyl group of heroin by the hydroxyl oxygen of

SUBMITTER: Qiao Y 

PROVIDER: S-EPMC3812942 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature