Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In addition to cytochrome P450, oxidation of drugs and other xenobiotics can also be mediated by non-P450 enzymes, the most significant of which are flavin monooxygenase, monoamine oxidase, alcohol dehydrogenase, aldehyde dehydrogenase, aldehyde oxidase and xanthine oxidase. This article highlights the importance of these non-P450 enzymes in drug metabolism. A brief introduction to each of the non-P450 oxidizing enzymes is given in this review and the oxidative reactions have been illustrated with clinical examples. Drug oxidation catalyzed by enzymes such as flavin monooxygenase and monoamine oxidase may often produce the same metablolites as those generated by P450 adn thus drug interactions may be difficult to predict without a clear knowledge of the underlying enzymology. In contrast, oxidation via aldehyde oxidase and xanthine oxidase gives different metabolites to those resulting from P450 hydroxylation. Although oxidation catalyzed by non-P450 enzymes can lead to drug inactivation, oxidation may be essential for the generation of active metabolite(s). The activation of a number of prodrugs by non-P450 enzymes is thus described. It is concluded that there is still much to learn about factors affecting the non-P450 enzymes in the clinical situation.
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PMID:The role of non-P450 enzymes in drug oxidation. 944 66

Although the majority of oxidative metabolic reactions are mediated by the CYP superfamily of enzymes, non-CYP-mediated oxidative reactions can play an important role in the metabolism of xenobiotics. Among the major oxidative enzymes, other than CYPs, involved in the oxidative metabolism of drugs and other xenobiotics, the flavin-containing monooxygenases (FMOs), the molybdenum hydroxylases [aldehyde oxidase (AO) and xanthine oxidase (XO)] and the FAD-dependent amine oxidases [monoamine oxidases (MAOs) and polyamine oxidases (PAOs)] are discussed in this minireview. In a similar manner to CYPs, these oxidative enzymes can also produce therapeutically active metabolites and reactive/toxic metabolites, modulate the efficacy of therapeutically active drugs or contribute to detoxification. Many of them have been shown to be important in endobiotic metabolism (e.g. XO, MAOs), and, consequently, interactions between drugs and endogenous compounds might occur when they are involved in drug metabolism. In general, most non-CYP oxidative enzymes (e.g. FMOs, MAOs) appear to be noninducible or much less inducible than the CYP system. Some of these oxidative enzymes exhibit polymorphic expression, as do some CYPs (e.g. FMO3). It is possible that the contribution of non-CYP oxidative enzymes to the overall metabolism of xenobiotics is underestimated, as most investigations of drug metabolism have been performed using experimental conditions optimised for CYP activity, although in some cases the involvement of non-CYP oxidative enzymes in xenobiotic metabolism has been inferred from not sufficient experimental evidence.
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PMID:FAD-dependent enzymes involved in the metabolic oxidation of xenobiotics. 2129 17