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Sunday, January 16, 2011

New FMO3 paper in pubmed by Italian researchers

Flavin-containing monooxygenase 3 (FMO3) is the gene repsonsible for genetic trimethylaminuria (due to deficiency of), so is of great interest to this blog. New medical research papers about FMO3 are surprisingly rare, given that it metabolizes hundreds of compounds in humans and is regarded as one of the 'drug metabolizing enzymes' and hence deficiency may cause adverse drug reactions.

In this case a new paper is published by a group Italian researchers and is probably only of indirect interest to genetic TMAU cases. It seems that the researchers have come up with a way to test FMO3 reactions in bovine cells in the laboratory. Whether this is a major step or similar methods are already used is not known. It would most likely be used to test if drugs are FMO3 substrates in any way.

Only the abstract is available to view for free.

Electro-catalysis by immobilised human flavin-containing monooxygenase isoform 3 (hFMO3).
Castrignanò S, Sadeghi SJ, Gilardi G.
Department of Human and Animal Biology, University of Torino, via Accademia Albertina, 13, 10123, Torino, Italy.
Abstract
Human flavin-containing monooxygenases are the second most important class of drug-metabolizing enzymes after cytochromes P450. Here we report a simple but functional and stable enzyme-electrode system based on a glassy carbon (GC) electrode with human flavin-containing monooxygenase isoform 3 (hFMO3) entrapped in a gel cross-linked with bovine serum albumin (BSA) by glutaraldehyde. The enzymatic electrochemical responsiveness is characterised by using well-known substrates: trimethylamine (TMA), ammonia (NH(3)), triethylamine (TEA), and benzydamine (BZD). The apparent Michaelis-Menten constant (K'(M)) and apparent maximum current (I'(max)) are calculated by fitting the current signal to the Michaelis-Menten equation for each substrate. The enzyme-electrode has good characteristics: the calculated sensitivity was 40.9 +/- 0.5 mA mol(-1) L cm(-2) for TMA, 43.3 +/- 0.1 mA mol(-1) L cm(-2) for NH(3), 45.2 +/- 2.2 mA mol(-1) L cm(-2) for TEA, and 39.3 +/- 0.6 mA mol(-1) L cm(-2) for BZD. The stability was constant for 3 days and the inter-electrode reproducibility was 12.5%. This is a novel electrochemical tool that can be used to investigate new potential drugs against the catalytic activity of hFMO3.

pubmed FMO3 abstract paper

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