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)

Reduced nicotinamide adenine dinucleotide (NADH):ferricyanide reductase and DT-diaphorase specific activity in total homogenates of rat liver are markedly decreased as a very early biochemical event of hepatocarcinogenesis induced by the carcinogen 2-acetylaminofluorene (AAF). A 50 to 75% decrease in NADH:ferricyanide reductase was observed after 1 day of AAF (0.025% in the diet) feeding and persisted throughout a 7-week continuum of AAF administration. Carcinogen added directly to cell extracts had no effect. Similar results were obtained with single injections of either AAF or diethylnitrosamine. Xanthine dehydrogenase was also reduced in liver following AAF administration to nearly the same extent as NADH:ferricyanide reductase and DT-diaphorase. Total NADH-cytochrome c reductase and mitochondrial activity as estimated from succinic dehydrogenase were not affected by carcinogen administration relative to basal dietary controls. The reduced nicotinamide adenine dinucleotide phosphate:cytochrome c reductase that functions in drug detoxification was elevated. With livers of animals fed 4-acetamidophenol, a hepatotoxin chemically related to AAF, small decreases were noted in NADH:ferricyanide reductase, but not in xanthine dehydrogenase nor in DT-diaphorase. Initial lowering of these activities in the livers of the carcinogen-treated animals is preceded by or concomitant with a reduction in the levels of extramitochondrial pyridine nucleotides known from other studies to result from DNA damage.
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PMID:Decreased NADH-oxidoreductase activities as an early response in rat liver to the carcinogen 2-acetylaminofluorene. 396 29

Recent evidence suggests that oxygen free radicals are largely responsible for the increased vascular permeability and early mucosal lesions associated with partial intestinal ischemia. It is postulated that oxygen radicals are produced by the reaction of the enzyme xanthine oxidase with hypoxanthine and molecular oxygen. In normal healthy cells, xanthine oxidase exists as a nicotinamide adenine dinucleotide-reducing dehydrogenase and not the oxygen radical-producing oxidase. In the intestine, dehydrogenase-to-oxidase conversion is nearly complete with less than 1 min of ischemia. Biochemical evidence from the intestine and liver indicate that ischemia-induced conversion of xanthine dehydrogenase to xanthine oxidase can be prevented by administration of protease inhibitors such as soybean trypsin inhibitor. In order to assess the role of proteases in oxygen radical-mediated ischemic injury to the small bowel, quantitative analyses of mucosal lesion development and vascular permeability were performed in autoperfused segments of cat ileum subjected to 1 or 3 h of ischemia and pretreated with 15 mg/kg (i.v.) soybean trypsin inhibitor. One hour of ischemia produced a significant increase in intestinal vascular permeability. The ischemia-induced increase in vascular permeability was significantly attenuated by soybean trypsin inhibitor pretreatment. Three hours of ischemia led to the development of mucosal lesions in untreated animals. Pretreatment with soybean trypsin inhibitor largely prevented the development of the mucosal lesions. The findings of our study are consistent with biochemical evidence that, during ischemia, proteases trigger the conversion of xanthine dehydrogenase to xanthine oxidase and thereby lead to oxygen radical production and subsequent tissue injury.
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PMID:Soybean trypsin inhibitor attenuates ischemic injury to the feline small intestine. 400 13

Cell-free particles from Pseudomonas rubescens have been shown to reduce hydroxocobalamin to vitamin B(12r). The particles are unable to reduce the B(12r) to B(12s). The reduction of hydroxocobalamin is dependent upon reduced nicotinamide adenine dinucleotide and is stimulated by flavin adenine dinucleotide. Cobinamide and diaquocobinamide were reduced at 25 and 10%, respectively, of the rate of hydroxocobalamin. Cyanocobalamin, coenzyme B(12), pseudovitamin B(12), and diaquopseudocobalamin were not reduced. Reduced nicotinamide adenine dinucleotide phosphate and flavin mononucleotide were not active. Diaphorase and xanthine oxidase activity were not present in the particulate fraction.
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PMID:Microbial degradation of corrinoids. VI. Reduction of hydroxocobalamin by cell-free particles from Pseudomonas rubescens. 438 87

In vitro assembly or complementation of a hybrid assimilatory nitrate reductase was attained by mixing a preparation of nitrate-induced N. crassa mutant nit-1 specifically with acid-treated (pH 2.5) bovine milk or intestinal xanthine oxidase, rabbit liver aldehyde oxidase, or chicken liver xanthine dehydrogenase. The complementation reaction specifically required induced nit-1, the only nitrate reductase mutant of Neurospora that lacked xanthine dehydrogenase and was unable to use hypoxathine or nitrate as a sole nitrogen source. The complementing activities of the above acid-treated enzymes correspond to their xanthine or aldehyde oxidizing activity profiles on sucrose density gradients. The resulting soluble, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-nitrate reductases are the same as the Neurospora wild type enzyme in sucrose density gradient profile, molecular weight, substrate affinities, and sensitivity to inhibitors and temperature. By analogy to a similar in vitro complementation of nitrate reductase in mixtures of induced nit-1 and individual nonalleic Neurospora mutants, or uninduced wild type, the complemented nitrate apparently consists of an inducible protein subunit (possessing inducible NADPH-cytochrome c reductase) furnished by nit-1 and a subunit from the acid-treated xanthine or aldehyde oxidizing system which can substitute for the constitutive component furnished by the other mutants or uninduced wild type. The data suggest that Neurospora nitrate reductase and the xanthine oxidizing system and aldehyde oxidase of animals, all of which are molybdenum-containing enzymes catalyzing the reduction of nitrate to nitrite, share a highly similar protein subunit.
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PMID:In vitro assembly of Neurospora assimilatory nitrate reductase from protein subunits of a Neurospora mutant and the xanthine oxidizing or aldehyde oxidase systems of higher animals. 439 66

Vanadate or molybdate strongly accelerate the cooxidation of NADH, or of reduced nicotinamide mononucleotide, by the xanthine oxidase plus xanthine reaction. Superoxide dismutase eliminated the effect of vanadate or molybdate, while catalase was without effect. It follows that vanadate or molybdate accelerate the oxidation of dihydropyridines by O-2. A stoichiometry of 4 NADH oxidized per O-2 introduced suggests a chain reaction for which a mechanism is proposed. These results provide an explanation for the reported stimulation, by vanadate, of NADH oxidation by biological membranes.
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PMID:Vanadate and molybdate stimulate the oxidation of NADH by superoxide radical. 608 31

The present paper describes that mammalian liver aldehyde oxidase is involved in the reduction of nicotinamide N-oxide to nicotinamide. Rabbit liver aldehyde oxidase supplemented with its electron donor exhibited a significant nicotinamide N-oxide reductase activity under anaerobic conditions. Liver cytosols from rabbits, hogs, guinea pigs, hamsters, rats and mice, all of them, similarly exhibited the N-oxide reductase activity in the presence of an electron donor of aldehyde oxidase, but not xanthine oxidase. The cytosolic N-oxide reductase activity was almost completely inhibited by menadione, an inhibitor of aldehyde oxidase.
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PMID:Involvement of liver aldehyde oxidase in the reduction of nicotinamide N-oxide. 623 71

To further delineate the mechanism responsible for the differences in xanthine oxidase activity in male and female Sprague-Dawley rats, a sensitive and specific radioimmunoassay (RIA) was developed for the measurement of hepatic xanthine oxidase. The RIA could detect as little as 5 mg of liver enzyme. Specificity of the RIA was confirmed by 1) Ouchterlony double immuno-diffusion in which a single precipitin band exhibited xanthine oxidase activity, when crude liver homogenate and an enzyme-specific stain were used; 2) parallelism between purified 125I-labeled xanthine oxidase and serial dilutions of crude liver homogenate; 3) a linear correlation between xanthine oxidase activity and the level of enzyme protein; and 4) a single protein band coincident with purified xanthine oxidase, when an immunoprecipitate prepared from antisera and crude liver homogenate was analyzed on sodium dodecyl sulfate (SDS) polyacrylamide gels. Whether xanthine oxidase activity was assayed in the absence of nicotinamide adenine dinucleotide (NAD+) (oxidase form) or in the presence of NAD+ (dehydrogenase), male values were consistently higher, and both forms of the enzyme correlated significantly with each other. When purified to homogeneity, neither form of the enzyme was appreciably affected by 17 beta-estradiol or testosterone propionate. When the RIA was employed, levels of hepatic xanthine oxidase were significantly greater in male than in female rats. We concluded from these data that increased xanthine oxidase activity in the male corresponds to a greater quantitative complement of xanthine oxidase protein. Furthermore, lower xanthine oxidase activity in the female cannot be explained by immunologically cross-reactive material without enzyme activity nor by a direct sex-steroid enzyme interaction.
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PMID:Quantitation of rat liver xanthine oxidase by radioimmunoassay. A mechanism for sex-specific differences. 689 96

The conversion of xanthine dehydrogenase to xanthine oxidase that produces oxygen radicals has been implicated in the ischemic injury to the myocardium and to the kidney. Xanthine dehydrogenase uses NAD as the electron acceptor to catalyze a reaction which does not produce any oxygen free radicals and may depress the conversion of xanthine dehydrogenase to xanthine oxidase. Nicotinamide is the preferred precursor for NAD. This study was conducted to examine the effect of an 18% casein diet supplemented with 0.5% nicotinamide on the activity of oxidoreductase and its two enzyme forms, xanthine dehydrogenase and xanthine oxidase, in kidney, heart and liver of female obese Zucker rats that spontaneously develop glomerulosclerosis, cardiomegaly and fatty liver. Lean litter mates were used as controls. Nicotinamide supplementation had no effect on the activities of these enzyme forms in the liver of either obese rats or lean rats. Obese rats fed the nicotinamide supplemented diet had higher activities of these enzyme forms in kidneys and hearts than unsupplemented diet fed obese rats, but this difference was not observed in lean rats. In unsupplemented rats, xanthine oxidase activity in the kidney was greater in lean rats than obese rats. Thus, the abnormalities observed in obese rats are unlikely attributable to the xanthine oxidase-mediated oxidant stress.
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PMID:Dietary nicotinamide supplementation increases xanthine oxidoreductase activity in the kidney and heart but not liver of obese Zucker rats. 761 99

The ability of O2 metabolites derived from the xanthine-xanthine oxidase system to inhibit mitochondrial function was examined using freshly isolated rat liver mitochondria. Under 2,4-dinitrophenol-uncoupled conditions, mitochondria exposed to free radicals exhibited a significant decrease in O2 consumption supported by NAD(+)-linked substrates, but showed almost no change in O2 consumption in the presence of succinate and ascorbate. Oxidative stress caused the loss of intramitochondrial nicotinamide nucleotides, and addition of NAD+ fully prevented any fall in O2 consumption with NAD(+)-linked substrates. The activity of electron-transfer complex I (NADH oxidase and NADH-cytochrome c oxidoreductase) and the energy-dependent reduction of NAD+ by succinate were unaltered by oxidative stress. Exposure to free radicals also had an uncoupling effect at all three coupling sites. The degree of mitochondrial swelling was closely correlated with the inhibition of State-3 oxidation of site-I substrates and with the increase in State-4 oxidation of succinate. The immunosuppressive agent cyclosporin A completely prevented the mitochondrial damage induced by oxygen free radicals (swelling, Ca2+ release, sucrose trapping, uncoupling and selective inhibition of the mitochondrial respiration of site-I substrates). The same protective effect was found when Ca2+ cycling was prevented, either by chelating Ca2+ with EGTA or by inhibiting Ca2+ reuptake with Ruthenium Red. These findings suggest that the deleterious effect of free radicals on mitochondria in the present experimental system was triggered by the cyclosporin A-sensitive and Ca(2+)-dependent membrane transition, and not by direct impairment of the mitochondrial inner-membrane enzymes.
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PMID:Oxidative damage to mitochondria is mediated by the Ca(2+)-dependent inner-membrane permeability transition. 769 Oct 56

The effects of Zn, Mg, Cr, Cu, and Mn aspartates, their commercial formulation Inzolen, and the individual commercial medicine Unizinc, on oxygen radical production by enzymes [xanthine oxidase, horseradish peroxidase, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase] and phagocytic cells (human blood leukocytes) have been studied. The formation of oxygen radicals was measured by luminol- and lucigenin-amplified chemiluminescence and by the reduction of cytochrome c. All these compounds (excluding Cr aspartate) turn out to be inhibitors of oxygen radical formation in the systems studied (excluding horseradish peroxidase). Their inhibitory activities were a consequence of both the scavenging of free radicals and the inhibition of xanthine oxidase and NADPH oxidase activities. As expected, the most active free-radical scavengers were transition metal Cu and Mn aspartates, which mimicked the activities of copper-zinc and manganese dismutases. However, surprisingly non-transition metal Zn and Mg aspartates were also able to scavenge oxygen radicals. It was suggested that the scavenging activities of Zn and Mg aspartates may be explained by affecting the rate of spontaneous dismutation of the superoxide ion. In addition, it was found that Zn aspartate is an efficient inhibitor of the formation of the most reactive hydroxyl radicals. These antioxidant properties of Zn aspartate make it important in medicine for the prevention and treatment of free radical pathologies.
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PMID:Study of antioxidant properties of metal aspartates. 774 Dec 42


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