<p>Flavin-containing monooxygenases (FMOs) constitute a family of xenobiotic-metabolising enzymes [<cite idref="PUB00000158"/>]. Using an NADPH cofactor and FAD prosthetic group,these microsomal proteins catalyse the oxygenation of nucleophilic nitrogen,sulphur, phosphorous and selenium atoms in a range of structurally diversecompounds. Five mammalian forms of FMO are now known and have been designatedFMO1-FMO5 [<cite idref="PUB00002642"/>, <cite idref="PUB00002611"/>, <cite idref="PUB00004772"/>, <cite idref="PUB00000516"/>, <cite idref="PUB00002834"/>].</p><p>The mRNA encoding FMO3 is abundant in adult liver and is also present, inlow abundance, in some foetal tissues. Thus, like FMO1, FMO3 is subjectto developmental and tissue-specific regulation, with a developmental switchin the expression of the genes taking place in the liver [<cite idref="PUB00001464"/>]. The deduced amino acid sequence of human FM03 includes the putative FAD-(GxGxxG) and NADP⁺ pyrophosphate-binding (GxGxxA) sites characteristic ofmammalian FMOs [<cite idref="PUB00000166"/>], a 'FATGY' motif that has also been observed in a rangeof siderphore biosynthetic enzymes [<cite idref="PUB00005489"/>], and a C-terminal hydrophobic segment that is believed to anchor the monooxygenase to the microsomal membrane [<cite idref="PUB00002549"/>].Mutations in human FMO3 impair N-oxygenation of xenobiotics and are responsible for the trimethylaminuria phenotype [<cite idref="PUB00002004"/>]. Three disease-causingmutations have been identified. Nonsense and missense mutations are associated with a severe phenotype and are also implicated in impairedmetabolism of other nitrogen- and sulphur-containing substrates, includingbiogenic amines, both clinically and when mutated proteins expressed fromcDNA are studied in vitro [<cite idref="PUB00002004"/>]. Human FMO3 thus plays a critical role in themetabolism of xenobiotic substrates and endogenous amines.</p> Flavin monooxygenase (FMO) 3