2006 paper : FMO3 'in action'

FMO3 is always of great interest to the blog, since it is one of the group of 'xenobiotic metabolizing enzymes' that deal with both external (xenobiotic) and internal compounds, either to neutralize for excretion or to 'activate' if needed in the main circulation. All the xenobiotic metabolizing enzymes are suspects in metabolic body odor, but FMO3 in particular since it is known to cause trimethylaminuria and also deals with 1,000s of smelly sulfide, amine and phosporous containing compounds.

In this 2006 paper, it looks as if this was the first time that FMO3 was finally 'seen in action' (i.e. it is finally demonstrated how it oxidizes a compound ... the reaction). Most readers know that the enzyme is dependent on vitamin B2 (riboflavin, as part of the FAD), but this paper explains in depth that it is also dependent on NADPH which itself uses niacin (vitamin B3) as a cofactor. This does not mean that niacin is likely to be of any benefit, and niacin itself can cause quite an undesirable symptom when taken as a supplement (the niacin flush, as well as a feeling of unease). There has been mention of cases where the FMO3 enzyme 'failure' is at the NADPH stage, but for the moment it is not known if this is of any significance.

Full paper 2006 : Mechanism of action of a flavin-containing monooxygenase

Interesting quotes from the paper :

Elimination of nonnutritional and insoluble compounds is a critical task for any living organism. Flavin-containing monooxygenases (FMOs) attach an oxygen atom to the insoluble nucleophilic compounds to increase solubility and thereby increase excretion...

... Flavin-containing monooxygenases (FMOs) and cytochromes P450 are two important microsomal (i.e. liver) proteins involved in the process of nonnutritional foreign compounds metabolism known as xenobiotics. Their main function is to add molecular oxygen to lipophilic compounds, making them soluble to ensure rapid excretion. FMOs oxygenate nucleophilic O, N, S, and Se atoms of a wide range of substrates, such as amines, amides, thiols, and sulfides...

...The mammalian FMO gene family contains five similar genes (FMO1 through FMO5). FMO1 and FMO3 are prominent isoforms expressed mainly in liver microsomes and in other tissues. FMO1 expression is higher in fetal liver, whereas FMO3 is more abundant in adult human. FMO2 is expressed in the lungs of nonhuman primates; FMO4 and FMO5 represent scarce isoforms (5, 6). Individuals with defective FMOs exhibit “fish odor syndrome” caused by excretion of trimethylamine instead of its oxygenated form, trimethylamine N-oxide in urine, sweat, and breath...

...Cytochrome P450s contain heme as a prosthetic group, whereas FMOs use FAD. These proteins need a cofactor NADPH in addition to the prosthetic group to accomplish their functional goal...

Scientists at the U.S. Department of Energy's Brookhaven National Laboratory, the New York Structural Biology Center, and SGX Pharmaceuticals, Inc., have determined the atomic crystal structure and functional mechanism of an enzyme essential for eliminating unwanted, non-nutritional compounds such as drugs, industrial chemicals, and toxic compounds from the body...

..."For FMOs, the end result -- that an oxygen atom gets added to make these compounds soluble -- is simple," Swaminathan says...

...People with defective FMOs might also suffer additional side effects from drugs, industrial compounds, or other chemicals.

http://www.physorg.com/news69420825.html