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Oxidation of Analogs of l ‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine by Monoamine Oxidases A and B and the Inhibition of Monoamine Oxidases by the Oxidation Products
Author(s) -
Youngster Stephen K.,
McKeown Kathleen A.,
Jin YuanZhen,
Ramsay Rona R.,
Heikkila Richard E.,
Singer Thomas P.
Publication year - 1989
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.1471-4159.1989.tb09250.x
Subject(s) - mptp , monoamine oxidase , monoamine oxidase b , chemistry , monoamine neurotransmitter , pyridinium , benzylamine , monoamine oxidase a , enzyme , stereochemistry , biochemistry , dopamine , medicinal chemistry , serotonin , endocrinology , biology , receptor , dopaminergic
Twenty analogs of l ‐methyl‐4‐phenyl‐l,2,3,6‐tet‐rahydropyridine (MPTP) were tested for their capacity to be xidized by pure monoamine oxidase‐A (MAO‐A) prepared from human placenta and pure monoamine oxidase‐B (MAO‐B) prepared from beef liver. Several of the MPTP analogs were very good substrates for MAO‐A, for MAO‐B, or for both and had low K m values and high turnover numbers. These values were similar to or even better than those of kynuramine and benzylamine, good substrates for MAO‐A and MAO‐B, respectively. MPTP had relatively low K m values for oxidation by both MAO‐A and MAO‐B. In contrast, the turnover number for MPTP oxidation by MAO‐B was considerably higher than the value for MAO‐A. The corresponding pyridinium species of MPTP and several of the MPTP analogs inhibited MAO‐A competitively with K i values at micromolar concentrations; in contrast the pyridinium species inhibited MAO‐B competitively at considerably higher concentrations (i.e., 100 μ M or greater K i values). The data provide information concerning the structural requirements for the oxidation of tetrahydropyridines by MAO‐A and MAO‐B and the inhibition of these enzymes by pyridini‐ums