Flavin-containing monooxygenase 3 (FMO3)

Flavin-containing monooxygenase 3 (FMO3) is a hepatic microsomal enzyme chiefly responsible for the N-oxidation of a broad range of xenobiotics, including drugs and environmental chemicals, and for converting trimethylamine to trimethylamine N-oxide in humans[1][2][3]. FMO3 is highly expressed in the adult human liver and contributes notably to phase I drug metabolism, catalyzing the oxygenation of soft nucleophile-containing substrates (e.g., those with nitrogen or sulfur). Genetic variants can radically impair or abolish its enzymatic activity, causing the metabolic disorder trimethylaminuria and leading to pronounced inter-individual variation in drug response and toxicity[2][3][1]. FMO3 also plays roles in liver aging processes and autophagy, and its expression or function may be modulated as part of hepatic adaptation to drugs, diet, or disease[5]. FMO3 activity is of pharmacological significance for the metabolism and clearance of several clinically important drugs, and is considered both a target and a critical determinant in pharmacogenomics and personalized medicine[2][4][1].

Other names

Dimethylaniline monooxygenase [N-oxide-forming] 3Trimethylamine monooxygenaseFMO 3FMOIIDimethylaniline oxidase 3FMO IIFMO form 2Hepatic flavin-containing monooxygenase 3TMAU

Substrate (drug/xenobiotic) N- or S-oxidation (main metabolic deactivation or activation pathway), Alteration of drug pharmacokinetics and clearance, Drug-drug interaction via enzymatic competition or inhibition