Mutation, polymorphism and perspectives for the future of human flavin-containing monooxygenase 3.
Flavin-containing monooxygenases (FMOs) catalyze NADPH-dependent monooxygenation of soft-nucleophilic nitrogen, sulfur, and phosphorous atoms contained within various drugs, pesticides, and xenobiotics. Flavin-containing monooxygenase 3 (FMO3) is responsible for the majority of FMO-mediated xenobiotic metabolism in the adult human liver. Mutations in the FMO3 gene can result in defective trimethylamine (TMA) N-oxygenation, which gives rise to the disorder known as trimethylaminuria (TMAU) or "fish-odour syndrome". To date 18 mutations of FMO3 gene have been reported that cause TMAU, and polymorphic variants of the gene have also been identified. Interindividual variability in the expression of FMO3 may affect drug and foreign chemical metabolism in the liver and other tissues. It is important therefore to study how base sequence variation of the FMO3 gene might affect the ability of individuals and different ethnic population groups to deal with the variety of environmental chemicals and pharmaceutical products that are substrates for FMO3.
Zhou
Jianhua
J
Department of Occupational and Environmental Health, Soochow University, 462# Zhuhui Road, Suzhou 215007, China. Electronic address: zjh_55@163.com.
Shephard
Elizabeth A
EA
Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom. Electronic address: e.shephard@ucl.ac.uk.
D000328:Adult; D002648:Child; D002675:Child, Preschool; D006801:Humans; D008099:Liver / Q000201:enzymology; D008744:Methylamines / Q000378:metabolism* / Q000652:urine; D009154:Mutation; D009812:Odorants; D010105:Oxygenases / Q000235:genetics*; D011110:Polymorphism, Genetic
D008744:Methylamines; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); C023336:trimethylamine