THE ROLE OF NON-P450 ENZYMES IN DRUG OXIDATION

In addition to cytochrome P450, oxidation of drugs and other xenobioti cs can also be mediated by non-450 enzymes, the most significant of wh ich 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 me tabolism. A brief introduction to each of the non-P450 oxidizing enzym es is given in this review and the oxidative reactions have been illus trated with clinical examples. Drug oxidation catalyzed by enzymes suc h as flavin monooxygenase and monoamine oxidase may often produced the same metabolites as those generated by P450 and thus drug interaction s may be difficult to predict without a clear knowledge of the underly ing enzymology, in contrast, oxidation via aldehyde oxidase and xanthi ne oxidase gives different metabolites to those resulting from P450 hy droxylation. Although oxidation catalyzed by non-P450 enzymes can lead to drug inactivation, oxidation may be essential for the generation o f active metabolite(s). The activation of a number of prodrugs by non- P450 enzymes is thus described. It is concluded that there is still mu ch to learn about factors affecting the non-P450 enzymes in the clinic al situation.