The flavin-containing monooxygenase (FMO) protein family specializes in the oxidation of xeno-substrates in order to facilitate the excretion of these compounds from living organisms.

[1] These enzymes can oxidize a wide array of heteroatoms, particularly soft nucleophiles, such as amines, sulfides, and phosphites.

[5] These monooxygenases are often misclassified because they share activity profiles similar to those of cytochrome P450 (CYP450), which is the major contributor to oxidative xenobiotic metabolism.

However, in the early 1970s, Dr. Daniel Ziegler from the University of Texas at Austin discovered a hepatic flavoprotein isolated from pig liver that was found to oxidize a vast array of various amines to their corresponding nitro state.

However, a group of researchers found a sixth FMO gene located on human chromosome 1.

[11][12] Developmental and tissue specific expression has been studied in several mammalian species, including humans, mice, rats, and rabbits.

[17] Unlike mammals, yeast (Saccharomyces cerevisiae) do not have several isoforms of FMO, but instead only have one called yFMO.

Instead, yFMO helps to fold proteins that contain disulfide bonds by catalyzing O2 and NADPH-dependent oxidations of biological thiols, just like mammalian FMO's.

yFMO is localized in the cytoplasm in order to maintain the optimum redox buffer ratio necessary for proteins containing disulfide bonds to fold properly.

FMOs have been implicated in the metabolism of a number of pharmaceuticals, pesticides and toxicants, by converting the lipophilic xenobiotics into polar, oxygenated, and readily excreted metabolites.

While FMO1-5 can be found in the brain, liver, kidneys, lungs, and small intestine, the distribution of each type of FMO differs depending on the tissue and the developmental stage of the person.

The degradation rate of these new drugs in an organism's system determines the duration and intensity of their pharmacological action.

However, recent efforts have been directed towards the development of drug candidates that incorporate functional groups that can be metabolized by FMOs.

In order to successfully screen hFMO3 in a high throughput fashion hFMO3 was successfully fixed to graphene oxide chips in order to measure the change in electrical potential generated as a result of the drug being oxidized when it interacts with the enzyme.

Some studies indicate that hypertension can develop when there are no organic osmolytes (i.e. TMAO) that can counteract an increase in osmotic pressure and peripheral resistance.

[33] The trimethylaminuria disorder, also known as fish odor syndrome, causes abnormal FMO3-mediated metabolism or a deficiency of this enzyme in an individual.

A person with this disorder has a low capacity to oxidize the trimethylamine (TMA) that comes from their diet to its odourless metabolite TMAO.

[34] When this happens, large amounts of TMA are excreted through the individual's urine, sweat, and breath, with a strong fish-like odor.

However, doctors recommend patients to avoid foods containing choline, carnitine, nitrogen, sulfur and lecithin.

[35][36] Yet, additional studies are imperative to elucidate what is the relationship between FMO function and these diseases, as well as to define these enzymes’ clinical relevance.