New FMO3 paper involving Dr John Cashman

Readers will know that Dr John Cashman of HBRI in San Diego has been at the forefront of FMO3/TMAU research for over a decade now, although overall there is little FMO3 research in general. Nowadays there is very little research seeming to be published on the subject other than by Dr Cashman.

For this new paper he has teamed up with a Japanese researcher who also has a history in TMAU/FMO3 research and with whom Dr Cashman has worked before. Reading the Abstract, this study seems to have been to largely find out the degree of FMO3 activity in childhood and involved testing 77 children ? The conclusions seem to be that trimethylamine in children seems to largely carried out by FMO3 and no part is played by FMO1 or FMO5. It needs clarifying, but it seems to suggest that children with just one 'flawed' copy of an FMO3 gene appeared to have variations in FMO3 development, at least in childhood ?

Developmental variations in metabolic capacity of flavin-containing mono-oxygenase 3 in childhood.
Shimizu M, Denton T, Kozono M, Cashman JR, Leeder JS, Yamazaki H.

Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan Human BioMolecular Research Institute, San Diego, CA 92121 Children's Mercy Hospital, Kansas City, MO 64108, USA.

Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The function of the human flavin-containing mono-oxygenase (FMO) has been shown to have large inter-individual variation related to trimethylaminuria. WHAT THIS STUDY ADDS • The study suggests that a developmental variation in functional metabolic capacity of FMO3 is occurring in childhood on the basis of in vivo phenotyping tests and in vitro liver microsomal determinations. AIM The aim of this study was to investigate intra- and inter-individual variations of functional metabolic capacity of flavin-containing mono-oxygenase (FMO) during childhood using trimethylamine N-oxygenation as a probe reaction. METHODS Trimethylamine N-oxygenation functional activity and presence of FMO1 (fetal form), FMO3 (adult form), and FMO5 (endogenous form) were immunochemically determined and compared in human liver microsomes obtained from children at various ages. As a control, the same parameters were studied with recombinant FMO1, FMO3 and FMO5 proteins as enzyme sources. Developmental variation in functional metabolic capacity of FMO was estimated by measuring urinary trimethylamine and its N-oxide in several individuals at different ages and in a group of 77 subjects in childhood. RESULTS There was a significant correlation between trimethylamine N-oxygenation functional activity and FMO3 expression levels in human liver microsomes (r= 0.71, P < 0.05, n= 9). Trimethylamine N-oxygenation was catalyzed largely by FMO3 and not by FMO1 or FMO5. On the basis of analysis of intra-individual observations and collective urine samples under daily dietary conditions it was possible that neonates or infants harbouring at least one non-inactive-allele of the FMO3 gene could have developmental FMO3 metabolic capacity in childhood. CONCLUSIONS Developmental variations in functional metabolic capacity of FMO3 in childhood were shown both on the basis of in vivo phenotyping tests and in in vitro liver microsomal determinations. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Abstract on Pubmed

Article on FMO3
Article on TMAU