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N-oxygenation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by the rat liver flavin-containing monooxygenase expressed in yeast cells.

Authors
  • Chiba, K
  • Kobayashi, K
  • Itoh, K
  • Itoh, S
  • Chiba, T
  • Ishizaki, T
  • Kamataki, T
Type
Published Article
Journal
European Journal of Pharmacology
Publisher
Elsevier
Publication Date
May 26, 1995
Volume
293
Issue
1
Pages
97–100
Identifiers
PMID: 7672012
Source
Medline
License
Unknown

Abstract

N-oxygenation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a dopaminergic neurotoxin, was studied using recombinant rat liver flavin-containing monooxygenase (FMO), FMO1A1, expressed in yeast cells. The mean (+/- S.D.) kinetic parameters of MPTP N-oxygenation were: Km = 1.8 +/- 0.5 microM, Vmax = 9.5 +/- 1.6 nmol/mg per min, and Vmax/Km = 4.6 +/- 0.5 ml/mg per min. n-Octylamine, an activator of FMO, enhanced the MPTP N-oxygenation activity by 51%, while methimazole, thiobenzamide and alpha-naphthylthiourea, alternate substrates of FMO, inhibited it by 27.4, 68.0 and 59.2%, respectively. The results indicate that MPTP is efficiently N-oxygenated by the recombinant rat liver FMO1A1, and that the responses to the modulators of FMO activity found in the recombinant rat liver FMO1A1 resemble those of mouse and rat liver microsomes as reported previously. The findings suggest that the recombinant FMO expressed in yeast cells is considered as a useful tool to study an involvement of FMO in the metabolism of environmental toxins or chemicals. In addition, FMO1A1 appears to be one of the predominant enzymes responsible for the N-oxygenation of MPTP at least in rat liver.

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