Flavin-containing monooxygenases: mutations, disease and drug response

Flavin-containing monooxygenases (FMOs) metabolize numerous foreign chemicals, including drugs, pesticides and dietary components and, thus, mediate interactions between humans and their chemical environment. We describe the mechanism of action of FMOs and insights gained from the structure of yeast...

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Bibliographic Details
Published in:Trends in pharmacological sciences (Regular ed.) 2008-06, Vol.29 (6), p.294-301
Main Authors: Phillips, Ian R, Shephard, Elizabeth A
Format: Article
Language:English
Subjects:
Advanced Basic Science
Humans
Mutation
Oxygenases - genetics
Oxygenases - metabolism
Pharmaceutical Preparations - metabolism
Polymorphism, Genetic
Schizosaccharomyces - enzymology
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Summary:Flavin-containing monooxygenases (FMOs) metabolize numerous foreign chemicals, including drugs, pesticides and dietary components and, thus, mediate interactions between humans and their chemical environment. We describe the mechanism of action of FMOs and insights gained from the structure of yeast FMO. We then concentrate on the three FMOs (FMOs 1, 2 and 3) that are most important for metabolism of foreign chemicals in humans, focusing on the role of the FMOs and their genetic variants in disease and drug response. Loss-of-function mutations of FMO3 cause the disorder trimethylaminuria. More common variants that decrease enzyme activity are associated with increased drug efficacy. Most humans are homozygous for a nonsense mutation that inactivates FMO2. But a substantial proportion of sub-Saharan Africans express functional FMO2 and, thus, are predicted to respond differently to drugs and other foreign chemicals.
ISSN:0165-6147
1873-3735
DOI:10.1016/j.tips.2008.03.004