FMO4

Flavin-containing monooxygenase 4 (FMO4) is a member of the flavin-containing monooxygenase (FMO) family of phase I metabolic enzymes. Like other FMOs, FMO4 catalyzes the NADPH- and O2-dependent oxidation of soft nucleophiles, aiding in the detoxification and metabolism of xenobiotics and some endogenous compounds. FMOs are typically localized in the endoplasmic reticulum and rely on a flavin adenine dinucleotide (FAD) cofactor to form a C4a-hydroperoxyflavin intermediate that inserts an oxygen atom into substrates.

FMO4 is one of several FMO isoforms encoded in mammalian genomes. Compared with FMO1–3, FMO4 has received relatively little study, and its tissue distribution, substrate range, and catalytic efficiency appear more limited or variable depending on species. In humans, FMO4 expression appears to be lower in liver relative to FMO3, with transcripts detected in several tissues in some studies, indicating a more tissue-restricted role. In vitro assays have shown that FMO4 can oxidize certain sulfur- and nitrogen-containing compounds, but the full spectrum of physiologically relevant substrates remains unclear.

Genetic variation in FMO4 has not been as extensively linked to disease or drug response as polymorphisms in FMO3. Nevertheless, as with other FMOs, interindividual differences in FMO4 expression or activity could influence disposition of xenobiotics in individuals who express functional enzyme.

Further research aims to define substrate specificity, tissue distribution, regulation, and clinical relevance of FMO4, as well as its evolutionary relationship to other FMOs.