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)

Considerable information is available concerning the oxidation of pteridine derivatives by bovine milk xanthine oxidase, but few investigations have been carried out on the oxidation of such compounds by mammalian liver xanthine oxidase and the related aldehyde oxidase. Xanthine oxidase, obtained from rat liver, oxidizes a variety of substituted amino- and hydroxypteridines in a manner identical to that previously observed for milk xanthine oxidase. For example, 2-aminopteridine and its 4- and 7-hydroxy derivatives were oxidized efficiently to 2-amino-4,7-dihydroxypteridine (isoxanthopterin) by the rat liver enzyme, and 4-aminopteridine and its 2- and 7-hydroxy derivatives were oxidized to 4-amino-2,7-dihydroxypteridine.4-Hydroxypteridine and the isomeric 2- and 7-hydroxypteridines were oxidized by rat liver xanthine oxidase to 2,4,7-trihydroxypteridine. Rabbit liver aldehyde oxidase, but not rat liver xanthine oxidase, was able to catalyze the oxidation in position 7 of 2,4-diaminopteridine and its 6-methyl and 6-hydroxymethyl derivatives. 2-Aminopteridine and 4-aminopteridine were both oxidized to the corresponding 7-hydroxy derivatives in the aldehyde oxidase system; 2-amino-4-hydroxypteridine appeared to be a minor product in the oxidation of 2-aminopteridine by rabbit liver aldehyde oxidase. Both aldehyde oxidase and xanthine oxidase were able to catalyze the oxidation of 2-amino-6,7-disubstituted pteridines to the corresponding 4-hydroxy derivatives; 4-hydroxy-6,7-disubstituted pteridines were oxidized in position 2 by both enzymes. 4-Amino-6,7-disubstituted pteridines were not oxidized by either enzyme. 2-Amino-4-methylpteridine was oxidized in position 7 by aldehyde oxidase but was not an effective substrate for xanthine oxidase; 2-hydroxypteridine and 7-hydroxypteridine were not oxidized to a detectably extent by aldehyde oxidase. All oxidations mediated by xanthine oxidase were strongly inhibited by allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine), and all oxidations mediated by aldehyde oxidase were inhibited by menadione (2-methyl-1,4-naphthoquinone). Rat liver xanthine oxidase and, to a lesser extent, rabbit liver aldehyde oxidase were inhibited by 4-chloro-6,7-dimethylpteridine; 2-amino-3-pyrazinecarboxylic acid inhibited xanthine oxidase but not aldehyde oxidase. The oxidations of 2- and 4-aminopteridines by aldehyde oxidase resulted in concomitant reduction of cytochrome c.
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PMID:Oxidation of selected pteridine derivatives by mamalian liver xanthine oxidase and aldehyde oxidase. 18 53

NADH-lipoamide dehydrogenase mobilized iron from ferritin under aerobic conditions. Superoxide dismutase strongly inhibited this mobilization, indicating that the superoxide radical is generated by the enzymatic reaction and release iron from ferritin. Addition of lipoamide as an electron acceptor to NADH-lipoamide dehydrogenase increased the release of iron from ferritin and this release was partially inhibited by superoxide dismutase. Similarly, addition of menadione (2-methyl-1, 4-naphthoquinone) as an electron acceptor to xanthine-xanthine oxidase promoted the release of iron from ferritin and this release was strongly inhibited by superoxide dismutase. These results suggest that dihydrolipoamide and semiquinone of menadione can react with oxygen to form the superoxide radical that mediates release of iron from ferritin.
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PMID:Superoxide-mediated release of iron from ferritin by some flavoenzymes. 215 90

The cytotoxicity of many xenobiotics is related to their ability to undergo redox reactions and iron dependent free radical reactions. We have measured the ability of a number of redox active compounds to release iron from the cellular iron storage protein, ferritin. Compounds were reduced to their corresponding radicals with xanthine oxidase/hypoxanthine under N2 and the release of Fe2+ was monitored by complexation with ferrozine. Ferritin iron was released by a number of bipyridyl radicals including those derived from diquat and paraquat, the anthracycline radicals of adriamycin, daunorubicin and epirubicin, the semiquinones of anthraquinone-2-sulphonate, 1,5 and 2,6-dihydroxyanthraquinone, 1-hydroxyanthraquinone, purpurin, and plumbagin, and the nitroaromatic radicals of nitrofurantoin and metronidazole. In each case, iron release was more efficient than with an equivalent flux of superoxide. Introduction of air decreased the rate of iron release, presumably because the organic radicals reacted with O2 to form superoxide. In air, iron release was inhibited by superoxide dismutase. Semiquinones of menadione, benzoquinone, duroquinone, anthraquinone 1,5 and 2.6-disulphonate, 1,4 naphthoquinone-2-sulphonate and naphthoquinone, when formed under N2, were unable to release ferrin iron. In air, these systems gave low rates of superoxide dismutase-inhibitible iron release. Of the compounds investigated, those with a single electron reduction potential less than that of ferritin were able to release ferritin iron.
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PMID:Release of iron from ferritin by semiquinone, anthracycline, bipyridyl, and nitroaromatic radicals. 275 90

Phenol and 1-naphthol, products of benzene and naphthalene biotransformation, are metabolized during O2- generation by xanthine oxidase/hypoxanthine and phorbol myristate acetate (PMA)-stimulated human neutrophils. The addition of 1-naphthol to xanthine oxidase/hypoxanthine incubations resulted in the formation of 1,4-naphthoquinone (1,4-NQ) whereas phenol addition yielded only small quantities of hydroquinone, catechol and a unidentified reducible product but not 1,4-benzoquinone. This formation of 1,4-NQ was dependent upon hypoxanthine, xanthine oxidase, and 1-naphthol and was inhibited by the addition of superoxide dismutase (SOD) demonstrating that the conversion was O2-mediated. During O2- generation by PMA-stimulated neutrophils, the addition of phenol interfered with luminol-dependent chemiluminescence and resulted in covalent binding of phenol to protein. Protein binding was 80% inhibited by the addition of azide or catalase to the incubations indicating that bioactivation was peroxidase-mediated. In contrast, the addition of 1-naphthol to PMA-stimulated neutrophils interfered with superoxide-dependent cytochrome c reduction as well as luminol-dependent chemiluminescence and also resulted in protein binding. Protein binding was only partially inhibited by azide or catalase. The addition of SOD in combination with catalase resulted in a significantly greater inhibition of binding when compared to that of catalase alone. The results of these experiments indicate that phenol and 1-naphthol are converted to reactive metabolites during superoxide generating conditions but by different mechanisms. The formation of reactive metabolites from phenol was almost exclusively peroxidase-mediated whereas the bioactivation of 1-naphthol could occur by two different mechanisms, a peroxidase-dependent and a direct superoxide-dependent mechanism.
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PMID:Metabolic activation of 1-naphthol and phenol by a simple superoxide-generating system and human leukocytes. 282 May 96

The addition of 2,3-dichloro-1,4-naphthoquinone (CNQ) to isolated mitochondria supplemented with GSSG resulted in a respiratory burst with the production of O2- and H2O2, and a decrease in the level of measurable disulfide. Superoxide generated by the xanthine oxidase system or by CNQ-treated mitochondria caused the reduction of GSSG to GSH. Both disulfide reductions were partially sensitive to exogeneous SOD. GSSG was also shown to interfere with the epinephrine - adrenochrome superoxide assay system. The findings reported herein support the conclusion that GSSG is capable of scavenging O2- and has the potential to scavenge other free radicals by a similar mechanism.
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PMID:A role for glutathione disulfide as a scavenger of oxygen radicals produced by 2,3-dichloro-1,4-naphthoquinone. 631 84

We have characterized a chemically reactive propranolol (PL) metabolite which binds to proteins in rat liver microsomes. During incubation with rat liver microsomes (1 mg of protein) fortified with an NADPH-generating system, 4-hydroxypropranolol (4-OH-PL) quickly disappeared from the reaction medium, but none of the possible metabolite peaks was detected under the high-performance liquid chromatographic conditions used. The consumption of 4-OH-PL depended on microsomes and NADPH. The reaction was not affected by inhibitors of cytochrome P450 or FAD monooxygenase, but was markedly diminished in the presence of cytosol and ascorbic acid. The effect of cytosol was inhibited by potassium cyanide but not by sodium benzoate or dimethyl sulfoxide, and was also not affected by heating at 60 degrees C for 30 min, suggesting that superoxide (SO) ion was involved in the reaction and that it was blocked by superoxide dismutase (SOD) present in the cytosol. Cu,Zn-SOD, purified from cytosol, effectively mimicked the suppressive effect of cytosol. Incubation of 4-OH-PL in an SO-generating system of xanthine and xanthine oxidase generated 1,4-naphthoquinone (1,4-NQ), which was identified by TLC, HPLC, and GC/MS. 1,4-NQ was also formed in microsomal incubates containing NADPH and small amounts of microsomes (below 0.1 mg of protein). These results indicate that 4-OH-PL is converted by SO, or some reactive oxygen species derived from it, to 1,4-NQ which binds to proteins and is one of the reactive metabolites of PL.
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PMID:Characterization of a chemically reactive propranolol metabolite that binds to microsomal proteins of rat liver. 754 55

Nitroxides stable radicals are unreactive toward most diamagnetic molecules, but readily undergo one-electron redox reactions with paramagnetic species such as free radicals and transition metals, thus serving as cell-permeable antioxidants. The cytotoxicity of juglone (5-hydroxy-1,4-naphthoquinone), like that of other naphthoquinones, requires bioreduction to yield the semiquinone which in turn reduces oxygen to O2.-. Therefore, nitroxides are expected to mitigate cytotoxicity of quinone-based xenobiotics, such as naphthoquinones. In the present study, in vitro scission of isolated DNA was induced upon juglone reduction by glutathione and Fe(II) ions, however, not by xanthine oxidase or cytochrome c reductase. The DNA scission was inhibited by nitroxides, catalase and chelating agents, though not by superoxide dismutase. Juglone was more toxic toward bacterial cells under hypoxia than under air. Nitroxides < or = 2 mM protected bacterial cells from juglone-induced toxicity under both aerobic and hypoxic conditions. The cytoprotective effect of lipophilic nitroxide was greater than that of hydrophilic ones. Catalase and metal chelating agents decreased juglone-induced cell killing, whereas H2O2 increased it. The mechanisms underlying the nitroxides protective effect involve (a) the reoxidation of reduced transition metal ions, (b) the selective radical-radical reaction with juglone semiquinone, and possibly (c) under aerobic condition catalytic removal of extra- and intracellular O2.-. The present results suggest also that the cell membrane rather than DNA is the main target of juglone toxicity.
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PMID:Effects of nitroxide stable radicals on juglone cytotoxicity. 803 50

Both phenylbutazon and mofebutazon inhibit oxidative fragmentation of the methionine derivative, 2-keto-4-methylthio-butyric acid (KMB) by xanthine oxidase--or diaphorase mediated OH radical production. Differentiation of the two non-steroidal antiinflammatory drugs is possible by means of determining oxygen reduction by xanthine oxidase or diaphorase in the presence of the naphthoquinone, juglone, where only mofebutazon shows an inhibitory effect.
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PMID:Antioxidative properties of phenazone derivatives: differentiation between phenylbutazon and mofebutazon. 821 10

Porcine and bovine lens GSTs were compared in the stability against various oxidative stress which is a major factor of cataract formation in order to clarify the role of lens glutathione S-transferase (GST) and its relation to cataractogenesis. Class pi porcine lens GST was inactivated reversibly by biological disulfides, cystine and cystamine, and also inactivated by active oxygen species such as O2- generated through xanthine-xanthine oxidase system and H2O2. On the other hand, class mu bovine lens GST was insensitive to such applied oxidative stress. Furthermore, 1,2-naphthoquinone, which is a metabolite of naphthalene and an actual inducer of naphthalene cataract, strongly inactivated porcine lens GST though it did not affect bovine enzyme. Thus, porcine and bovine lens GSTs had different sensitivity to various oxidative stress which could induce cataract formation. The results suggest that the differential expression of GST isozymes among animals may explain the variation in the cataract formation caused by oxidative stress.
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PMID:Difference in glutathione S-transferase response to oxidative stress between porcine and bovine lens. 847 85

Exposure of mesangial cells to superoxide, generated by the hypoxanthine/xanthine oxidase system or by the redox cycler 2,3-dimethoxy-1,4-naphthoquinone caused a concentration-dependent amplification of interleukin (IL)-1beta-stimulated nitrite production. The effect of superoxide was accompanied by an increase in inducible nitric oxide synthase (iNOS) protein and iNOS mRNA levels. Incubation of mesangial cells with superoxide alone did not induce iNOS expression. To elucidate whether the increase of iNOS expression is due to transcriptional upregulation we fused a 4.5-kb genomic iNOS fragment that contains the transcriptional start site of the rat iNOS gene to a luciferase reporter gene. In transient transfection studies, superoxide caused a 10-fold augmentation of iNOS promoter activity in IL-1beta-challenged mesangial cells. Our data identify superoxide as a co-stimulatory factor amplifying cytokine-induced iNOS gene expression and subsequent nitric oxide (NO) synthesis.
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PMID:Potentiation of nitric oxide synthase expression by superoxide in interleukin 1 beta-stimulated rat mesangial cells. 975 54


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