Faculty Collaboration Database

Human hepatic flavin-containing monooxygenases 1 (FMO1) and 3 (FMO3) developmental expression. Pediatr Res 2002 Feb;51(2):236-43

Date

01/26/2002

Pubmed ID

11809920

DOI

10.1203/00006450-200202000-00018

Scopus ID

2-s2.0-0036157094 (requires institutional sign-in at Scopus site)   213 Citations

Abstract

The flavin-containing monooxygenases (FMOs) are important for the metabolism of numerous therapeutics and toxicants. Six mammalian FMO genes (FMO1-6) have been identified, each exhibiting developmental and tissue- and species-specific expression patterns. Previous studies demonstrated that human hepatic FMO1 is restricted to the fetus whereas FMO3 is the major adult isoform. These studies failed to describe temporal expression patterns, the precise timing of the FMO1/FMO3 switch, or potential control mechanisms. To address these questions, FMO1 and FMO3 were quantified in microsomal fractions from 240 human liver samples representing ages from 8 wk gestation to 18 y using Western blotting. FMO1 expression was highest in the embryo (8-15 wk gestation; 7.8 +/- 5.3 pmol/mg protein). Low levels of FMO3 expression also were detectable in the embryo, but not in the fetus. FMO1 suppression occurred within 3 d postpartum in a process tightly coupled to birth, but not gestational age. The onset of FMO3 expression was highly variable, with most individuals failing to express this isoform during the neonatal period. FMO3 was detectable in most individuals by 1-2 y of age and was expressed at intermediate levels until 11 y (12.7 +/- 8.0 pmol/mg protein). These data suggest that birth is necessary, but not sufficient for the onset of FMO3 expression. A gender-independent increase in FMO3 expression was observed from 11 to 18 y of age (26.9 +/- 8.6 pmol/mg protein). Finally, 2- to 20-fold interindividual variation in FMO1 and FMO3 protein levels were observed, depending on the age bracket.

Author List

Koukouritaki SB, Simpson P, Yeung CK, Rettie AE, Hines RN

Authors

Sevasti Koukouritaki PhD Research Scientist II in the Pediatrics department at Medical College of Wisconsin
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aging
Child
Child, Preschool
Embryo, Mammalian
Female
Fetus
Gene Expression Regulation, Developmental
Gene Expression Regulation, Enzymologic
Gestational Age
Humans
Infant
Infant, Newborn
Isoenzymes
Liver
Male
Microsomes, Liver
Oxygenases