【摘 要】
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As the most active metabolite of heroin,6-monoacetylmorphine(6-MAM)can penetrate into the brain for the rapid onset of heroin effects(Scheme 1).The primary enzymes responsible for the metabolism of 6-
【机 构】
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The College of Chemistry and Molecular Engineering,Center of Computational Chemistry,Zhengzhou Unive
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As the most active metabolite of heroin,6-monoacetylmorphine(6-MAM)can penetrate into the brain for the rapid onset of heroin effects(Scheme 1).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 by performing first-principles quantum mechanical/molecular mechanical free energy calculations.It has been demonstrated that the two enzymatic reaction processes follow the similar catalytic reaction mechanism,and the free energy barriers calculated for the AChE-and BChE-catalyzed reactions are in good agreement with the experimentally derived activation free energies(17.5 and 20.7 kcal/mol for the AChE-and BChE-catalyzed reactions,respectively).The obtained structural and mechanistic insights could be valuable for use in future rational design of a novel therapeutic treatment of heroin abuse.
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