Studies on the molecular mechanism of bioactivation of the selective nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Studies on the molecular mechanism of bioactivation of the selective nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
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发表时间：
1985-05
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影响因子：
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通讯作者：
K. Chiba;Lisa A. Peterson;K. Castagnoli;Anthony Trevor;N. Castagnoli
中科院分区：
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作者：
K. Chiba;Lisa A. Peterson;K. Castagnoli;Anthony Trevor;N. Castagnoli
研究了单胺氧化酶b在大鼠脑线粒体制剂中对黑纹状体毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的生物活化作用。在H2O和D2O中培养的分离物显示出1-甲基-4-苯基-2,3-二氢吡啶物种MPDP+的化学电离质谱特征，MPDP+是MPTP向1-甲基-4-苯基吡啶代谢物（MPP+）生物转化的中间体，之前在体外和体内实验中都有表征。通过将代谢产物与合成的MPDP+高氯酸盐（CIO4-）的二极管阵列紫外光谱图进行比较，并从MPTP和氰化钠的线粒体共孵育混合物中分离出氰基加合物，进一步表征了MPDP+。MPDP+ CIO4-被证明会歧化为MPP+和MPTP，这一反应表明该分子可能参与与多巴胺的氧化还原反应，从而导致神经毒性氧化产物。
Detailed studies have been carried out on the monoamine oxidase B-catalyzed bioactivation of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by rat brain mitochondrial preparations. Isolates of incubation mixtures run in H2O and D2O displayed chemical ionization mass spectral characteristics expected for the 1-methyl-4-phenyl-2,3-dihydropyridinium species MPDP+, a proposed intermediate in the biotransformation of MPTP to the 1-methyl-4-phenylpyridinium metabolite (MPP+) previously characterized in both in vitro and in vivo experiments. Further characterization of MPDP+ was achieved by comparison of the diode array UV spectral tracings of the metabolite with synthetic MPDP+ perchlorate (CIO4-) and by the isolation of a cyano adduct from mitochondrial coincubation mixtures of MPTP and sodium cyanide. MPDP+ CIO4- was shown to undergo disproportionation to MPP+ and MPTP, a reaction which suggests that this molecule may participate in redox reactions with dopamine that could lead to neurotoxic oxidation products.