Metabolism of the neurotoxin in MPTP by human liver monoamine oxidase B

FEBS Lett. 1985 Jul 8;186(2):224-8. doi: 10.1016/0014-5793(85)80713-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Cattle
  • Humans
  • Isoenzymes / isolation & purification
  • Isoenzymes / metabolism*
  • Kinetics
  • Liver / enzymology*
  • Mitochondria, Liver / enzymology
  • Monoamine Oxidase / isolation & purification
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors
  • Neurotoxins / metabolism*
  • Pyridines / metabolism*

Substances

  • Isoenzymes
  • Monoamine Oxidase Inhibitors
  • Neurotoxins
  • Pyridines
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Monoamine Oxidase