MONOAMINE OXIDASES AND RELATED AMINE OXIDASES AS PHASE-I ENZYMES IN THE METABOLISM OF XENOBIOTICS

To date most of the interest in oxidative metabolism of xenobiotics ha s been devoted to the role of the microsomal cytochrome P-450 system a nd to establish the basis for classifying and naming P450 enzymes. The contribution of amine oxidases to the metabolism of xenobiotics has b een largely neglected, with the exception of the contribution of monoa mine oxidases (MAOs) to the metabolism of exogenous tyramine and the s tudies of the ''cheese effect'' produced as the result of ingestion of large amounts of tyramine-containing foods under particular condition s. A review of the involvement of the mitochondrial MAOs in drug metab olism was published in 1988. Since that time, considerable additional evidence has appeared in the literature to support the contribution of MAOs to drug metabolism. In addition, the involvement of other amine oxidases in the metabolism of foreign compounds has been established. A second review on the contribution of amine oxidases to the metabolis m of xenobiotics was therefore published in 1994. On an arbitrary basi s, the heterogeneous class of amine oxidases can be divided into two t ypes according to their prosthetic group: the flavine-adenine dinucleo tide (FAD)-dependent amine oxidases (Monoamine Oxidase and Polyamine O xidase) and the amine oxidases not containing FAD (Semicarbazide-sensi tive amine oxidases). In this overview, the contributions of these two types in xenobiotic metabolism are considered separately.