Reversible inhibition and mechanism-based irreversible inactivation of monoamine oxidases by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
Reversible inhibition and mechanism-based irreversible inactivation of monoamine oxidases by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
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1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 对单胺氧化酶的可逆抑制和基于机制的不可逆失活。
DOI：
10.1016/s0006-291x(85)80219-9
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发表时间：
1985
影响因子：
3.1
通讯作者：
D. Crabtree
中科院分区：
文献类型：
--
作者：
T. Singer;J. Salach;D. Crabtree
已经提出（Chibaet al.，生物化学、生物物理Res. Communs.（1984）120，574），MPTP（1-甲基-4-苯基-1，2，3，6-四氢吡啶）的神经毒性作用（其在人类和其它灵长类动物中引起帕金森病症状）是由于MPTP被脑中的单胺氧化酶B氧化而产生的化合物。我们最近报道，单胺氧化酶A和B都将MPTP氧化为MPDP+，即2，3-二氢吡啶鎓形式，并且该反应伴随着酶的时间依赖性不可逆失活。在两种形式的单胺氧化酶中，B酶氧化MPTP更快，并且对失活也更敏感。我们现在希望报告MPTP及其氧化产物MPDP+和MPP+（4-苯基吡啶鎓形式）也是单胺氧化酶A和B（尤其是前者）的有效可逆竞争性抑制剂，并且对A酶的抑制顺序为MPDP+> MPP+> MPTP，而对B酶的抑制顺序为MPTP > MPDP+> MPP+。我们进一步报告的光谱变化和同位素掺入伴随着不可逆的失活。
It has been suggested (Chibaet al., Biochem. Biophys. Res. Communs. (1984) 120, 574) that the neurotoxic effects of MPTP (l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), which causes Parkinsonian symptoms in humans and other primates, are due to compounds resulting from the oxidation of MPTP by monoamine oxidase B in the brain. We reported recently that both monoamine oxidase A and B oxidize MPTP to MPDP+, the 2,3-dihydropyridinium form and that the reaction is accompanied by time-dependent, irreversible inactivation of the enzymes. Of the two forms of monoamine oxidase, the B enzyme oxidizes MPTP more rapidly and is also more sensitive to inactivation. We now wish to report that MPTP, as well as its oxidation products, MPDP+and MPP+, the 4-phenylpyridinium form, are also potent reversible, competitive inhibitors of both monoamine oxidase A and B, particularly the former, and that the order of inhibition for the A enzyme is MPDP+> MPP+> MPTP, while for the B enzyme MPTP > MPDP+> MPP+. We further report on the spectral changes and isotope incorporation accompanying the irreversible inactivation.
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
发表时间：
1984
影响因子：
3.1
作者：
Salach,JI;Singer,TP;CastagnoliJr,N;Trevor,A
通讯作者：
Trevor,A