Tamoxifen (TAM) is an antiestrogen and currently used extensively for breast cancer therapy. FMOs, especially FMO1 can N-oxidze TAM to tamoxifen N-oxide (TNO). TNO can be reduced back to TAM by the P450 system. TNO appears to be just as potent as TAM but with fewer side-effects so this metabolic cycling could play a part in the use of TNO in the treatment of breast cancer.

FMO1:FAD (flavin monooxygenase 1 : FAD complex) catalyzes the reaction of hypotaurine (HTAU) with NADPH + H+ and O2 to form taurine (TAU), NADP+, and water (Veeravalli et al. 2020).

Flavin-containing monooxygenases (FMOs) are the second family of microsomal oxidative enzymes with broad and overlapping specificity. The major reactions FMOs catalyze are nucleophilic hetero-atom compounds such as nitrogen, sulfur or phosphorus as the hetero-atom to form N-oxides, S-oxides or P-oxides respectively. Despite the functional overlap with cytochrome P450s, the mechanism of action differs. FMOs bind and activate molecular oxygen before the substrate binds to the enzyme (picture). They also require flavin adenosine dinucleotide (FAD) as a cofactor. Unlike cytochrome P450 enzymes, FMOs are heat-labile, a useful way to distinguish which enzyme system is at work for researchers studying metabolism. Also, FMOs are not inducible by substrates, unlike the P450 enzymes.\n(1) NADPH binds to the enzyme and reduces the prosthetic group FAD to FADH₂. NADP⁺ remains bound to the enzyme.\n(2) Incorporation of molecular oxygen to form a hydroperoxide.\n(3) A peroxide oxygen is transferred to the substrate.\n(4) Water is released.\n(5) NADP⁺ dissociates returning the enzyme to its initial state.\n\nTo date, there are 6 isozymes of FMO (FMO1-6) in humans, the most prominent and active one being FMO3. The FMO6 gene does not encode for a functional enzyme although it has the greatest sequence similarity with FMO3 (71%), whilst the others range from 50-58% sequence similarity with FMO3. FMO1-3 are the ones that exhibit activity towards nucleophiles, the others are insignificant in this respect (Cashman 2003, Krueger & Williams 2005).