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 has been devoted to the role of the microsomal cytochrome P-450 system and to establish the basis for classifying and naming P450 enzymes. The contribution of amine oxidases to the metabo
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Department of Preclinical Development and Human Pharmacology, Zambon Group, Bresso, Italy 2 Department of Biochemistry, Trinity College, Dublin, Ireland
Summary. To date most of the interest in oxidative metabolism of xenobioties has been devoted to the role of the mierosomal eytoehrome P-450 system and to establish the basis for dassifying and naming P450 enzymes. The eontribution of amine oxidases to the metabolism of xenobioties has been largely negleeted, with the exeeption of the eontribution of monoamine oxidases (MAOs) to the metabolism of exogenous tyramine and the studies of the "eheese effeet" produeed as the result of ingestion of large amounts of tyramine-containing foods under partieular eonditions. A review of the involvement of the mitoehondrial MAOs in drug metabolism was published in 1988. Sinee that time, eonsiderable additional evidenee 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 seeond review on the eontribution of amine oxidases to the metabolism of xenobioties was therefore published in 1994. On an arbitrary basis, the heterogeneous dass of amine oxidases ean be divided into two types aeeording to their prosthetie group: the ftavineadenine dinudeotide (FAD)-dependent amine oxidases (Monoamine Oxidase and Polyamine Oxidase) and the amine oxidases not eontaining FAD (Semiearbazide-sensitive amine oxidases). In this overview, the eontributions of these two types in xenobiotie metabolism are eonsidered separately.
1. Introduction The metabolie reaetions of foreign compounds may be dassified very broadly into four types oeeurring in two distinet phases. The first phase of metabolism involves either oxidation, reduetion or hydrolysis. This is followed by the seeond phase in whieh the original eompound or metabolite is linked with an endogenous moleeule in a synthetie or eonjugation reaetion. To date most of the interest in oxidative metabolism of xenobioties has been devoted to the role of the mierosomal eytoehrome P-450 system. Inereasing attention, however, is being given to the involvement of the eytosolie and J. P. M. Finberg et al. (eds.), MAO — The Mother of all Amine Oxidases © Springer-Verlag Wien 1998
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M. Strolin Benedetti and K. F. Tipton
mitochondrial enzymes known as the molybdenum hydroxylases (Beedham, 1985) and to the flavin-containing microsomal oxidases (Ziegler, 1988) in the metabolism of xenobiotics. In contrast, the contribution of amine oxidases to the metabolism of xenobiotics has been largely neglected, with the exception of the contribution of monoamine oxidases (MAOs) to the metabolism of exogenous tyramine and the studies of the "cheese effect" produced as the result of ingestion of large amounts of tyramine-containing foods under particular conditions. A review of the involvement of the mitochondrial MAOs in drug metabolism was published in 1988 (Strolin Benedetti et al., 1988). Since that time, considerable
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