Oxidation of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by monoamine oxidases A and B and suicide inactivation of the enzymes by MPTP.
Oxidation of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by monoamine oxidases A and B and suicide inactivation of the enzymes by MPTP.
复制标题
单胺氧化酶 A 和 B 氧化神经毒性胺 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP)，并通过 MPTP 自杀灭活酶。
DOI：
10.1016/0006-291x(84)90614-4
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发表时间：
1984
影响因子：
3.1
通讯作者：
Trevor,A
中科院分区：
文献类型：
--
作者：
Salach,JI;Singer,TP;CastagnoliJr,N;Trevor,A
1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）是一种类似哌替啶的麻醉剂的热分解产物，被药物滥用者用作合成海洛因，导致人类帕金森病症状和猴子黑质变性。MPTP被脑线粒体制备物氧化的过程被丙炔苯丙胺和帕吉林阻断，这意味着单胺氧化酶B的催化作用。本文证明，从牛肝中分离的纯MAO B氧化MPTP的速度为苄胺的38%，具有相当的Km值。此外，从人胎盘中分离的MAO A以犬尿胺的约12%的速率将MPTP氧化成相同的产物，同样具有相当的Km值。后一反应被氯吉林阻断。两种形式的MAO通过遵循一级动力学的过程被MPTP逐渐灭活。这种渐进的失活以及在凝胶排阻色谱后MAO B的活性没有显著再生的事实表明与酶形成共价加合物。因此，MPTP似乎是MAO的自杀灭活剂。
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a thermal breakdown product of a meperidine-like narcotic analgetic used by drug abusers as a synthetic heroin, causes Parkinsonian symptoms in humans and degeneration of the substantia nigra in monkeys. MPTP is oxidized by brain mitochondrial preparations in a process which is blocked by deprenyl and pargyline, implying catalysis by monoamine oxidase B. The present paper demonstrates that pure MAO B isolated from beef liver oxidizes MPTP 38% as fast as benzylamine with a comparable Kmvalue. Additionally, MAO A, isolated from human placenta, oxidizes MPTP to the same product at about 12% of the rate of kynuramine, again with a comparable Kmvalue. The latter reaction is blocked by clorgyline. Both forms of MAO are progressively inactivated by MPTP by a process which follows first order kinetics. This progressive inactivation and the fact that the activity of MAO B is not significantly regenerated following gel exclusion chromatography suggest the formation of a covalent adduct with enzyme. Thus, MPTP appears to be a suicide inactivator of MAO.