Developmental variations in metabolic capacity of flavin-containing mono-oxygenase 3 in childhood

Br J Clin Pharmacol. 2011 Apr;71(4):585-91. doi: 10.1111/j.1365-2125.2010.03876.x.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Antioxidants / metabolism*
  • Child Development
  • Female
  • Gene Expression / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Metabolism, Inborn Errors / metabolism
  • Methylamines / metabolism
  • Methylamines / urine
  • Microsomes, Liver / metabolism*
  • Oxygenases / genetics
  • Oxygenases / metabolism*
  • Polymorphism, Genetic / genetics
  • Regression Analysis

Substances

  • Antioxidants
  • Methylamines
  • Oxygenases
  • dimethylaniline monooxygenase (N-oxide forming)
  • trimethylamine

Supplementary concepts

  • Trimethylaminuria