Enzymological Aspects of the Actions of the Parkinsonism-Inducing Neurotoxin MPTP
The role of the B-form of monoamine oxidase (MAO-B) in converting the compound MPTP (1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine) to neurotoxic metabolites is well-established from studies on the protection afforded by selective inhibitors of that enzyme (for reviews see Singer et al., 1987; Kinemuchi et al., 1987). The neurotoxic metabolite appears to be the 4-electron oxidation product, the 4-phenylpyridinium ion (MPP(+)). It has been proposed that the action of this compound as an inhibitor of mitochondrial oxidative phosphorylation from NADH may account for its neurotoxicity (Nicklas et al., 1985; Ramsay et al., 1986).
KeywordsMonoamine Oxidase Brain Mitochondrion Mitochondrial Oxidative Phosphorylation Partition Ratio Deuterium Isotope Effect
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