METABOLISM OF THE NEUROTOXIN IN MPTP BY HUMAN-LIVER MONOAMINE OXIDASE-B
METABOLISM OF THE NEUROTOXIN IN MPTP BY HUMAN-LIVER MONOAMINE OXIDASE-B
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DOI：
10.1016/0014-5793(85)80713-4
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发表时间：
1985-01-01
期刊：
影响因子：
3.5
通讯作者：
BROSSI, A
中科院分区：
文献类型：
--
作者：
FRITZ, RR;ABELL, CW;BROSSI, A
利用单胺氧化酶B (monoamine oxidase B, MAO B)，包括纯人肝脏MAO B：单克隆抗体复合物，将神经毒素1‐甲基‐4‐苯基‐1,2,3,6‐四氢吡啶（MPTP）氧化为二氢吡啶MPDP+和吡啶MPP+。MPTP和苯胺（MAO B的首选底物）的Km值分别为316 μM和64 μM。4‐苯基‐1,2,3,6‐四氢吡啶（PTP）是MPTP的非衍生物，也是底物（Km,app= 221μM）。MPDP+MPTP和MPP+，而不是PTP，被发现是MAO B的不可逆抑制剂。我们的研究支持这样的假设，即灵长类动物大脑中MPTP被MAO B氧化为MPDP+，然后转化为MPP+，这是黑质中发现的一种主要代谢物。
The neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) was oxidized to dihydropyridine MPDP+and pyridine MPP+by preparations of monoamine oxidase B (MAO B), including pure human liver MAO B:monoclonal antibody complex.Km,appvalues for MPTP and benzylamine, a preferred MAO B substrate, were 316 and 64 μM, respectively. 4‐Phenyl‐1,2,3,6‐tetrahydropyridine (PTP), the nor derivative of MPTP, was also a substrate (Km,app= 221μM). MPDP+MPTP, and MPP+, but not PTP, were found tobe irreversible inhibitors of MAO B. Our studies support the hypothesis that MPTP is oxidized in primate brain by MAO B to MPDP+which is then converted to MPP+a major metabolite found in the substantia nigra.