Drug metabolism by flavin-containing monooxygenases of human and mouse.
Flavin-containing monooxygenases (FMOs) play an important role in drug metabolism. Areas covered: We focus on the role of FMOs in the metabolism of drugs in human and mouse. We describe FMO genes and proteins of human and mouse; the catalytic mechanism of FMOs and their significance for drug metabolism; differences between FMOs and CYPs; factors contributing to potential underestimation of the contribution of FMOs to drug metabolism; the developmental and tissue-specific expression of FMO genes and differences between human and mouse; and factors that induce or inhibit FMOs. We discuss the contribution of FMOs of human and mouse to the metabolism of drugs and how genetic variation of FMOs affects drug metabolism. Finally, we discuss the utility of animal models for FMO-mediated drug metabolism in humans. Expert opinion: The contribution of FMOs to drug metabolism may be underestimated. As FMOs are not readily induced or inhibited and their reactions are generally detoxifications, the design of drugs that are metabolized predominantly by FMOs offers clinical advantages. Fmo1(-/-),Fmo2(-/-),Fmo4(-/-)mice provide a good animal model for FMO-mediated drug metabolism in humans. Identification of roles for FMO1 and FMO5 in endogenous metabolism has implications for drug therapy and initiates an exciting area of research.
a Institute of Structural and Molecular Biology , University College London , London , UK.|b School of Biological and Chemical Sciences , Queen Mary University of London , London , UK.
Ian R
IR
Phillips
a Institute of Structural and Molecular Biology , University College London , London , UK.
Elizabeth A
EA
Shephard
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D051379:Mice; D023421:Models, Animal; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D013045:Species Specificity
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)
Animal model; CYP; FMO; cytochrome P450; drug metabolism; flavin-containing monooxygenase; genetic variant; human; knockout mouse; mouse