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Studies on the Oxidation of the Dopaminergic Neurotoxin 1‐Methyl‐4‐Phenyl‐1,2,5,6‐Tetrahydropyridine by Monoamine Oxidase B
Author(s) -
Heikkila Richard E.,
Manzino Lawrence,
Cabbat Felicitas S.,
Duvoisin Roger C.
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb05522.x
Subject(s) - mptp , monoamine oxidase , chemistry , monoamine oxidase b , neurotoxin , dopaminergic , in vivo , pharmacology , pargyline , biochemistry , dopamine , endocrinology , enzyme , biology , microbiology and biotechnology
1‐Methyl‐4‐phenyl‐ 1,2,5,6 ‐tetrahydropyridine (MPTP) is a chemical that, after injection into experimental animals, including mice and monkeys, causes a degeneration of the nigrostriatal pathway. We carried out experiments designed to study the in vitro oxidation of MPTP by mouse brain mitochondrial preparations. MPTP was actively oxidized by the mitochondrial preparations, with K m and V max values very similar to those of benzyl amine, a typical substrate for MAO‐B. MPTP was oxidized considerably better than many of its analogs, even those with relatively minor structural changes. Several monoamine oxidase inhibitors (MAOI) were potent inhibitors of MPTP oxidation, and there was a highly significant correlation between the capacity of the MAOI tested to inhibit MPTP oxidation and benzylamine oxidation. There was no correlation between the capacity of the MAOI to inhibit MPTP oxidation and their capacity to inhibit the oxidation of tryptamine, a substrate for MAO‐A. In other experiments, MPTP was an excellent substrate for pure MAO‐B, prepared from bovine liver. All of these data. combined with the fact that MAO‐B inhibitors can protect against MPTP‐induced dopami nergic neurotoxicity in vivo. point to an important role for MAO‐B in MPTP metabolism in vivo.