Reaction pathways and free energy profiles for cholinesterase-catalyzed hydrolysis of 6-monoacetylmorphine.

ABSTRACT: As the most active metabolite of heroin, 6-monoacetylmorphine (6-MAM) can penetrate into the brain for the rapid onset of heroin effects. The primary enzymes responsible for the metabolism of 6-MAM to the less potent morphine in humans are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The detailed reaction pathways for AChE- and BChE-catalyzed hydrolysis of 6-MAM to morphine have been explored, for the first time, in the present study by performing first-principles quantum mechanical/molecular mechanical free energy calculations. It has been demonstrated that the two enzymatic reaction processes follow similar catalytic reaction mechanisms, and the whole catalytic reaction pathway for each enzyme consists of four reaction steps. According to the calculated results, the seco

SUBMITTER: Qiao Y 

PROVIDER: S-EPMC4040391 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature