Metabolism of the neurotoxin in MPTP by human liver monoamine oxidase B
- 8 July 1985
- journal article
- Published by Wiley in FEBS Letters
- Vol. 186 (2) , 224-228
- https://doi.org/10.1016/0014-5793(85)80713-4
Abstract
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. K m,app values 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 (K m,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.Keywords
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