Oxidation of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by monoamine oxidases A and B and suicide inactivation of the enzymes by MPTP.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a thermal breakdown product of a meperidine-like narcotic analgetic used by drug abusers as a synthetic heroin, causes Parkinsonian symptoms in humans and degeneration of the substantia nigra in monkeys. MPTP is oxidized by brain mitochondrial preparations in a process which is blocked by deprenyl and pargyline, implying catalysis by monoamine oxidase B. The present paper demonstrates that pure MAO B isolated from beef liver oxidizes MPTP 38% as fast as benzylamine with a comparable Km value. Additionally, MAO A, isolated from human placenta, oxidizes MPTP to the same product at about 12% of the rate of kynuramine, again with a comparable Km value. The latter reaction is blocked by clorgyline. Both forms of MAO are progressively inactivated by MPTP by a process which follows first order kinetics. This progressive inactivation and the fact that the activity of MAO B is not significantly regenerated following gel exclusion chromatography suggest the formation of a covalent adduct with enzyme. Thus, MPTP appears to be a suicide inactivator of MAO.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors; D010084:Oxidation-Reduction; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011725:Pyridines / Q000378:metabolism*
D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D011725:Pyridines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase