Like P450s, flavin monooxygenases (FMO, EC 18.104.22.168) are NADPH-dependent enzymes that couple a two-electron reduction of oxygen to water with two-electron oxidation of its substrates. With FMO, this chemistry occurs at the noncovalently bound flavin center of the molecule. During catalysis, the FAD prosthetic group is activated to a C4a-hydroperoxo species that carries out oxidative reactions on nucleophilic centers. FMOs have a restricted portfolio of reactions that they can catalyze because the activated FAD is a weaker oxidant than the activated perferryl species of P450. Consequently, their role in oxidative drug metabolism is much less pronounced than that of the P450s. FMOs typically form mostly N-oxide and S-oxide metabolites39 from xenobiotics and also serve an important physiological function in converting trimethylamine to trimethylamine N-oxide.40
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