The role of the flavin-containing monooxygenase (EC 1.14.13.8) in the metabolism and mode of action of agricultural chemicals

Abstract

1. The flavin-containing monooxygenase (FMO) (EC 1.14.13.8) is a versatile enzyme that catalyses the monooxygenation of a large number of xenobiotic soft nucleophiles ranging from inorganic ions to organic compounds with nitrogen, sulphur, phosphorus or selenium heteroatoms.

2. The substrate specificity relative to agricultural chemicals is discussed and compared with that of the cytochrome P-450-dependent monooxygenase system. The relative activity of these two enzymes towards common substrates varies from substrate to substrate and from tissue to tissue as is shown in the case of the insecticide, phorate and the hepatotoxicant, thiobenzamide.

3. The products of FMO action may be chemically different (e.g. nicotine) to those from P-450, or the two enzymes may produce different isomers of the same product (e.g. phorate).

4. Recent studies have demonstrated that, in the rabbit, the FMOs from liver and lung are different gene products which differ not only in primary sequence but also in physical, catalytic and immunochemical properties. These studies are being extended to include other tissues such as skin and brain.

5. Immunocytochemical localization of FMO in lung and skin correlates well with measurements of the oxidation of methimazole, a specific FMO substrate.