FMO2

FMO2, or flavin-containing monooxygenase 2, is an enzyme that belongs to the flavin-containing monooxygenase (FMO) family. Like other FMOs, FMO2 catalyzes the NADPH-dependent oxygenation of soft nucleophiles, such as nitrogen, sulfur, and phosphorus-containing compounds, to form more polar products that can be more readily excreted. The reaction typically uses flavin adenine dinucleotide (FAD) as a cofactor and occurs in the endoplasmic reticulum of cells.

In humans, FMO2 expression is enriched in lung tissue, with lower levels detected in other tissues. This lung-dominant distribution suggests a role in the metabolism of inhaled xenobiotics and certain systemic compounds, contributing to the detoxification of a range of environmental chemicals and pharmaceuticals.

Genetics and variation: The FMO2 gene exhibits notable human genetic variation. A common loss-of-function mutation truncates the protein in many individuals, resulting in little or no functional FMO2 activity. An active form, often referred to as FMO2.1, is relatively more prevalent in people of African ancestry, while functional activity is less common in many other populations. Several additional alleles with altered activity have been described, reflecting a spectrum of enzymatic capability among individuals.

Clinical and research relevance: Variation in FMO2 activity can influence the capacity to metabolize certain xenobiotics in the lungs, potentially affecting responses to inhaled drugs or environmental chemicals and possibly modulating susceptibility to some toxicants. The precise substrates and the full physiological significance of FMO2 are the subjects of ongoing research, with attention to how genetic diversity shapes metabolism, pharmacology, and health outcomes.