MOLECULAR CLONING OF MOUSE LIVER FLAVIN CONTAINING MONOOXYGENASE (FMO1) cDNA AND CHARACTERIZATION OF THE EXPRESSION PRODUCT : METABOLISM OF THE NEUROTOXIN, 1,2,3,4- TETRAHYDROISOQUINOLINE (TIQ)

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概要

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• A mouse liver cDNA clone, MFMO1, coding for a flavin-containing monooxygenase (FMO) was isolated. This cDNA clone encoded a protein of 532 amino acids. Based upon its predicted amino acid sequence, this clone was assumed to belong to the FMO1 subfamily. The deduced amino acid sequence showed 94, 84, 83, and 83% identity with FMO1s of rats, pigs, rabbits and humans, respectively, while it showed only 50-59% identity with human FMO3 and FMO4, rabbit FMO2, FMO3, FMO4 and FMO5,and guinea-pig FMO2. RNA blot analysis showed that the mouse FMO1 was also expressed in the lung and kidney and to lesser extents in the heart, spleen, testis and brain. Mouse FMO1 expressed in yeast showed activities of thiobenzamide S-oxidation, and NADPH oxidation associated with the S- or N-oxidation of chlorpromazine, N,N-dimethylaniline, N,N-dimethyl-hydrazine, imipramine, nicotine, thioacetamide, thiourea and trimethylamine. Moreover, 1,2,3,4-tetrahydroisoquinoline (TIQ), a substance known to induce a parkinsonism-like syndrome in monkeys, was also metabolized by the mouse FMO1. The Km values for chlorpromazine, imipramine and TIQ were determined to be 2.4, 16.0, 435 mM, respectively. This is the first report to show that an expressed FMO can metabolize a neurotoxin, TIQ.

• 日本トキシコロジー学会の論文
• 1997-02-25

著者

• ITOH Susumu

  Division of Drug Metabolism, Faculty of Pharmaceuti-cal Sciences, Hokkaido University

• KAMATAKI Tetsuya

  Division of Drug Metabolism, Faculty of Pharmaceuti-cal Sciences, Hokkaido University

• Kamataki T

  Hokkaido Univ. Sapporo Jpn

• Kamataki Tetsuya

  Department Of Pharmacology School Of Medicine Keio University:department Of Analytical Biochemistry

• Kamataki Tetsuya

  Division Of Analytical Biochemistry Faculty Of Pharmaceutical Sciences Hokkaido University

• Itoh S

  Division Of Cellular Physiology Faculty Of Pharmaceutical Sciences Osaka University

• Itoh Susumu

  Division Of Drug Metabolism Faculty Of Pharmaceutical Sciences Hokkaido University

• Itoh Kunio

  Division Of Drug Metabolism Faculty Of Pharmaceutical Sciences Hokkaido University

• Nakamura Kaori

  Bozo Research Center Inc.

• NAKAMURA Kaori

  Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University

• KIMURA Teruyuki

  Sandoz Pharmaceuticals Ltd.

• Itoh Susumu

  Division Of Cellular Physiology Faculty Of Pharmaceutical Sciences Osaka University

• Kamataki Tetsuya

  Lab. Drug Metab. Fac. Pharm. Sci. Hokkaido University

• Kimura T

  Sankyo Co. Ltd. Shizuoka Jpn

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