Metabolism of the neurotoxin in MPTP by human liver monoamine oxidase B.
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, Km,app values for MPTP and benzylamine, a preferred MAO B substrate, were 316 and 64 microM, respectively. 4-Phenyl-1,2,3,6-tetrahydropyridine (PTP), the nor derivative of MPTP, was also a substrate (Km,app = 221 microM). MPDP+, MPTP, and MPP+, but not PTP, were found to be 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.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002417:Cattle; D006801:Humans; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology; D008995:Monoamine Oxidase / Q000302:isolation & purification / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors; D009498:Neurotoxins / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism*
D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D009498:Neurotoxins; D011725:Pyridines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase