Developmental and tissue-specific expression of human flavin-containing monooxygenases 1 and 3

Abstract

Substantial changes occur in drug and toxicant disposition during early life stages that can impact therapeutic efficacy and adverse reactions to drugs and toxicants. Of the many parameters involved, alterations in drug metabolism are of major importance. Although the cytochrome P450-dependent monooxygenases are accepted as playing a substantial role in drug and toxicant metabolism, the flavin-containing monooxygenases (FMOs) also have an important role. Apparently unique to the human, FMO3 is the most abundant FMO family member in the adult human liver, whereas FMO1 dominates in most animal models. However, early studies documented that FMO1 is the most abundant FMO enzyme in the human fetal liver, whereas FMO3 is essentially absent. This review focuses on recent studies characterising human FMO ontogeny and, in particular, the switch in hepatic FMO enzyme expression. Because it is so closely related, tissue-specific expression patterns also are examined. Finally, a summary of what is known in animal models is presented as a point of comparison.

Keywords::

• developmental pharmacology
• drug metabolism
• flavin-containing monooxygenase
• FMO
• ontogeny
• tissue-specific expression