Human hepatic flavin-containing monooxygenases 1 (FMO1) and 3 (FMO3) developmental expression.
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.
Koukouritaki
Sevasti B
SB
Department of Pediatrics, Birth Defects Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Simpson
Pippa
P
Yeung
Catherine K
CK
Rettie
Allan E
AE
Hines
Ronald N
RN
D000293:Adolescent; D000328:Adult; D000375:Aging; D002648:Child; D002675:Child, Preschool; D004622:Embryo, Mammalian / Q000502:physiology; D005260:Female; D005333:Fetus / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007527:Isoenzymes; D008099:Liver / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)