Tissue expression and ontogenic development

As with P450, FMO isoforms are ubiquitously distributed in the animal kingdom and in the body where the highest concentrations are generally found in the liver, although certain species have high enzyme concentrations in the lung (rabbit) and kidney (mouse). FMO1 is the major liver form in most experimental animals, but is not detectable in adult human liver, where FMO3 and FMO5 are the major isoforms. FMO1 is relatively abundant in human kidney and present at much lower levels in the intestine and the brain.47 FMO5 and FMO2 are the major isoforms expressed, at the mRNA level, in human small intestine and lung respectively,48 although the functional significance of these two enzymes in these organs is unclear.

Hepatic FMO1 is restricted to the fetus, peaking in the early embryo, and decreasing steadily within 3 days postpartum (Table 4).49 Conversely, hepatic FMO3 protein is not detectable in the fetal state, and its onset of expression after birth can be slow. As noted above, FMO3 is necessary for the conversion of trimethylamine to its nonodoriferous N-oxide metabolite, so delayed onset of expression of this enzyme may contribute to cases of transient childhood trimethylaminuria.50 The temporal switch for these FMO isoforms contrasts with that observed for CYP3A7 and CYP3A4/5, in which the suppression of CYP3A7 expression is accompanied by a simultaneous increase in CYP3A4/5, and the net hepatic CYP3A content remains constant.51 The relatively high expression levels of FMO1 during prenatal development and the embryonic periods, in particular, might argue for a role for FMO1 in the metabolism of endogenous substrates that are important for development, but this remains to be determined.

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