Introduction to Biotransformation (Metabolism) - Pesticide Biotransformation and Disposition - page 63

Figure 4.3 The catalytic cycle for flavin-containing monooxygenase-catalyzed monooxygenase
reactions.
Recent studies have identified five forms of FMO (FMO1-FMO5), which are
differentially expressed with respect to species and tissue ( Lawton and Philpot, 1995;
Lawton et al., 1994 ). Each species that has been examined by analysis of genomic
DNA appears to contain the same set of FMO genes ( Lawton et al., 1994 ). Although
the FMO family possesses multiple isoforms, the number of such forms is small com-
pared to that of the CYP superfamily. While the FMO isoforms all have the same cata-
lytic mechanism, marked differences exist in substrate specificity.
The importance of the FMO in pesticide metabolism was established when it
was discovered that the FMO oxidizes a variety of thioether-containing pesticides
( Cherrington et al., 1998a,b; Hajjar and Hodgson, 1980, 1982a,b; Levi and Hodgson,
1992; Smyser et al., 1985; Tynes and Hodgson, 1985 ). It has since been shown that
the FMO is capable of oxidative desulfuration (oxon formation) of certain phos-
phonate insecticides, such as fonofos, through a mechanism distinct from that of