Role of FMO3 Gene

The flavin-containing monooxygenase 3 (FMO3) gene encodes the enzyme FMO3, pivotal in the biotransformation of numerous endogenous and exogenous compounds, including trimethylamine (TMA) and xenobiotics.

FMO3 is predominantly expressed in the liver, where it facilitates the conversion of TMA to its non-odorous metabolite, trimethylamine N-oxide (TMAO), via N-oxygenation. This enzymatic process entails the transfer of an oxygen atom from molecular oxygen (O2) to the substrate molecule, catalyzed by the flavin adenine dinucleotide (FAD) cofactor.

Consequently, TMA undergoes oxidation, forming TMAO, essential for eliminating excess TMA and preventing the malodor associated with Trimethylaminuria (TMAU).

Beyond TMA, FMO3 exhibits broad substrate specificity, metabolizing various xenobiotics such as drugs, environmental toxins, and dietary constituents. For instance, tamoxifen, a widely used breast cancer medication, undergoes FMO3-mediated oxidation to produce its active metabolite, endoxifen.

Additionally, benzydamine, a nonsteroidal anti-inflammatory drug (NSAID), is metabolized by FMO3 to generate its active metabolite, N-oxide benzydamine.

Furthermore, FMO3 catalyzes S-oxygenation, a process where sulfur-containing compounds are oxidized, exemplified by the conversion of thioethers into sulfoxides.

This detoxification mechanism enhances water solubility and promotes the excretion of xenobiotics, significantly contributing to the metabolism and clearance of drugs and xenobiotics.

Last updated : March 2024