Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic ethanol oxidation increases according to its concentration and is raised to near-saturation levels of alcohol dehydrogenase (ADH); therefore, re-oxidation of NADH becomes rate limiting in ethanol metabolism by the liver. Adenosine is able to increase liver ethanol oxidation in both in vivo and in vitro conditions; the enhancement being related with the capacity of the nucleoside to accelerate the transport of cytoplasmic reducing equivalents to mitochondria, by modifying the subcellular distribution of the malate-aspartate shuttle components. In the present study, we explored the putative effects of adenosine and other purines on liver ethanol oxidation mediated by non-ADH pathways. Using the model of high precision-cut rat liver slices, a pronounced increase of ethanol oxidation was found in liver slices incubated with various intermediates of the purine degradation pathway, from adenosine to uric acid (175-230%, over controls). Of these, urate had the strongest (230%), whereas xanthine had the less pronounced effect (178% over controls). The enhancement was not abolished by 4-methylpyrazole, indicating that the effect was independent of alcohol dehydrogenase. Conversely, aminotriazole, a catalase inhibitor, completely abolished the effect, pointing out that this enhanced ethanol oxidation is mediated by catalase activity. It is concluded that the H2O2 needed for catalase activity is derived from the oxidation of (hypo)xanthine by xanthine oxidase and the oxidation of urate by uricase. The present and previous data led us to propose that, depending on the metabolic conditions, adenosine might be able to stimulate the metabolism of ethanol through different pathways.
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PMID:Catalase increases ethanol oxidation through the purine catabolism in rat liver. 2852 16

The major non-P450 enzymes involved in the oxidative metabolism of drugs are: the flavin- containing monooxygenase (FMO), the monoamine oxidase (MAO), the aldehyde oxidase (AO), the xanthine oxidase (XO), the alcohol dehydrogenase (ADH) and the aldehyde dehydrogenase (ALDH). In recent years, the role of non-P450 enzymes in drug oxidative metabolism has garnered increasing attention. However, the contribution of non-P450 enzymes to the drug oxidative metabolism is possibly underestimated in many cases, as most metabolism studies in drug discovery and lead optimization are conducted using in vitro test systems related to P450 enzymes. In this article, these non-P450 enzymes in terms of catalyzed reaction types, common substrates, gene polymorphism and drug interaction are reviewed, and the in vitro models and factors for non-P450-mediated oxidative metabolism are summarized. Similar to P450 enzymes, non-P450 enzymes can directly catalyze the oxidation of drugs, yielding therapeutically active metabolites or toxic metabolites. These enzymes can also oxidize the toxic metabolites, generated from P450-catalyzed reaction, to nontoxic metabolites. In general, most non-P450 enzymes (such as FMO and MAO) appear to be much less inducible than P450 enzymes.
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PMID:[Research advances in non-P450-mediated drug oxidative metabolism]. 2991 69


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