New review of FAD-dependent enzymes including FMO3

Readers will know that published TMAU papers are very rare but it seems there is slightly more interest in the enzyme that causes genetic TMAU, that is enzyme FMO3. FMO3 is probably involved in many drug metabolizing processes, but currently seems to be overlooked by the pharma industry. This new review is written by a researcher at a smaller pharma company based in Belgium. Only the abstract is free to view. FMO3 is dependent on flavin adenine dinucleotide (FAD), which it gets from modifying riboflavin (vitamin B2). This is why taking B2 is sometimes suggested for those with genetic TMAU to see if it can stimulate any residual FMO3. Whether it is effective in any cases or at all is not known.

There are quite a few FAD dependent enzymes that oxidize compounds, which this article elaborates on. Most of these articles are greatly involved in detoxifying or activating compounds in the body and are especially present in the liver. The group of CYP enzymes (which are not FAD dependent, and depend on a niacin derivative)are usually regarded the important toxin/activation oxidizing 'players', so it is nice to see FMO3 get a mention.

Ann Pharm Fr. 2011
FAD-dependent enzymes involved in the metabolic oxidation of xenobiotics.
Strolin Benedetti M.

UCB Pharma SA, 420, rue d'Estienne-d'Orves, 92705 Colombes, France.
Abstract

Although the majority of oxidative metabolic reactions are mediated by the CYP superfamily of enzymes, non-CYP-mediated oxidative reactions can play an important role in the metabolism of xenobiotics. Among the major oxidative enzymes, other than CYPs, involved in the oxidative metabolism of drugs and other xenobiotics, the flavin-containing monooxygenases (FMOs), the molybdenum hydroxylases [aldehyde oxidase (AO) and xanthine oxidase (XO)] and the FAD-dependent amine oxidases [monoamine oxidases (MAOs) and polyamine oxidases (PAOs)] are discussed in this minireview. In a similar manner to CYPs, these oxidative enzymes can also produce therapeutically active metabolites and reactive/toxic metabolites, modulate the efficacy of therapeutically active drugs or contribute to detoxification. Many of them have been shown to be important in endobiotic metabolism (e.g. XO, MAOs), and, consequently, interactions between drugs and endogenous compounds might occur when they are involved in drug metabolism. In general, most non-CYP oxidative enzymes (e.g. FMOs, MAOs) appear to be noninducible or much less inducible than the CYP system. Some of these oxidative enzymes exhibit polymorphic expression, as do some CYPs (e.g. FMO3). It is possible that the contribution of non-CYP oxidative enzymes to the overall metabolism of xenobiotics is underestimated, as most investigations of drug metabolism have been performed using experimental conditions optimised for CYP activity, although in some cases the involvement of non-CYP oxidative enzymes in xenobiotic metabolism has been inferred from not sufficient experimental evidence.

Abstract on Pubmed