New HBRI FMO research paper

Dr John Cashman of the Human Biomolecular Research Institute in San Diego is probably the most prolific researcher (of the few researching) of the FMO group of enzymes. This month he has published another research paper. It looks as if it is to do with FMO enzyme sources for research labs, so likely has no direct connection with TMAU other than it may make research on the FMO enzymes easier in the future.

Oligomerization and kinetic characterization of human FMO3 and FMO5 expressed as maltose binding protein fusions.
Reddy RR, Ralph EC, Motika MS, Zhang J, Cashman JR.

1 Human Biomolecular Research Institute;
Abstract
The flavin-containing monooxygenase (FMO) family of enzymes oxygenates nucleophilic xenobiotics and endogenous substances. Human FMO3 and FMO5 are the predominant FMO forms in adult liver. These enzymes are naturally membrane-bound, and recombinant proteins are commercially available as microsomal preparations from insect cells (i.e., Supersome FMO). Alternatively, FMO3 has previously been expressed as a soluble protein, through use of an N-terminal maltose binding protein (MBP) fusion. In the current study, MBP fusions of both human FMO3 and FMO5 were prepared to >90% purity in the presence of detergent, characterized for biochemical and kinetic parameters, and the parameters were compared to those of Supersome FMO samples. Although MBP-FMO enzymes afforded lower rates of turnover compared with the corresponding Supersome FMOs, both types of FMO showed identical substrate dependencies and similar responses to changes in assay conditions. Interestingly, the FMO3 enzymes showed a 2-fold activation of k(cat)/K(m) n the presence of Triton X-100. Oligomeric analysis of MBP-FMO3 also showed disassociation from a high-order oligomeric form to a monomeric status in the presence of Triton X-100. This report serves as the first direct comparison between Supersome FMOs and the corresponding MBP-fusions, and the first report of a detergent-based activation of k(cat)/K(m) that corresponds to changes in oligomerization.

The full paper can be read for free here:
http://dmd.aspetjournals.org/content/34/1/19.long

One interesting note was that FMO5 seems to be quite abundant in the small intestine. It does not seem to be known what role FMO5 plays, although often people with TMAU feel they have mild 'gut issues'. Perhaps FMO5 plays a detoxifying role in the gut, without which the ecology tends to get unfavorably 'out of control'

Update : It now seems it is unlikely FMO5 has an important role in humans. It seems to be very 'substrate specific' and deals with very few substrates, and although the RNA may be found in adult human cells, this does not mean it turns into FMO5 protein.