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)

The status of xanthine oxidase in ethanol-induced liver injury has been investigated in the rat, by acute and chronic ethanol treatments. A 38% increase of the enzyme O-form was observed after repeated ethanol administration. Chronic intoxication caused a significant decrease of total xanthine oxidase activity after both prolonged ethanol feeding and life span ethanol ingestion. The intermediate D/O-form of xanthine oxidase (that can act either as an oxidase or as a dehydrogenase, being able to react with O2 as well as with NAD+ as electron acceptor) increased 5.5-fold after prolonged ethanol feeding.
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PMID:Xanthine oxidase status in ethanol-intoxicated rat liver. 269 Jun 70

The conversion of xanthine dehydrogenase to a free radical producing oxidase is an important component of oxygen-mediated tissue injury. Current assays for these enzymes are of limited sensitivity, making it difficult to analyze activities in organ biopsies or cultured cells. The xanthine oxidase-catalyzed conversion of pterin (2-amino-4-hydroxypteridine) to isoxanthopterin provides the basis for a fluorometric assay which is 100-500 times more sensitive than the traditional spectrophotometric assay of urate formation from xanthine. Enzyme activity as low as 0.1 pmol min-1 ml-1 can be measured with the fluorometric pterin assay. Xanthine oxidase is assayed in the presence of pterin only, while combined xanthine dehydrogenase plus oxidase activity is determined with methylene blue which replaces NAD+ as an electron acceptor. The relative proportions and specific activities of xanthine oxidase and dehydrogenase determined by the fluorometric pterin assay are comparable with the spectrophotometric measurement of activities present in rat liver, intestine, kidney, and plasma. The assay has been successfully applied to brain, human kidney, and cultured mammalian cells, where xanthine dehydrogenase and oxidase activities are too low to detect spectrophotometrically.
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PMID:A sensitive fluorometric assay for measuring xanthine dehydrogenase and oxidase in tissues. 275 92

Concentrations of 1-, 3-, and 7-methylxanthine and their uric acid metabolites were measured in plasma and brain affusate 20 min after ip injection of the monomethylxanthines into rats. 3-Methylxanthine was not metabolized to 3-methyluric acid. Similar concentrations of 7-methylxanthine and 7-methyluric acid were detected in both plasma and brain affusate. The oxidation of 1-methylxanthine to 1-methyluric acid occurred so rapidly that the parent compound could not be detected in plasma, and only low concentrations could be detected in brain. Similar patterns in rates of metabolism (1-methyl- greater than 7-methyl- much greater than 3-methylxanthine) were observed in both intact animals and perfused rat liver. The metabolism of 1-methylxanthine to 1-methyluric acid in perfused livers could be explained on the basis of the dehydrogenase form of xanthine oxidase. This conclusion is supported by the observations that the stoichiometry between oxygen utilization and methylurate formation was not consistent with catalysis by the oxidase form of the enzyme and that NADH formed from the metabolism of ethanol strongly inhibited 1-methylxanthine oxidation. In perfused liver, anaerobic conditions decreased rates of 1-methylxanthine metabolism by only 24%. These data demonstrate the presence of oxidizing substrates other than oxygen and NAD+ which are capable of maintaining xanthine oxidase activity during hypoxia. Moreover, rates of 1-methylxanthine metabolism during anoxia could be restored to normal, aerobic values by the infusion of pyruvate, which increased hepatic levels of NAD+. These data demonstrate that changes in the hepatic oxidation-reduction state may dramatically affect rates of xanthine oxidase-dependent metabolism in intact cells.
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PMID:In vivo and in vitro 1-methylxanthine metabolism in the rat. Evidence that the dehydrogenase form of xanthine oxidase predominates in intact perfused liver. 288 2

3 alpha-Hydroxysteroid dehydrogenase (EC 1.1.1.50) from Pseudomonas testosterone was inactivated by superoxide radicals generated by the aerobic xanthine oxidase reaction. Superoxide dismutase, NAD+, bovine serum albumin and histidine and cysteine as free amino acids partially protected the enzyme from inactivation. NADH-binding properties were determined by fluorescence spectroscopy, and no variation was found between native enzyme and the unmodified fraction of the partly inactivated one. The fluorescence emission maximum for the completely inactivated enzyme was shifted 10 nm to a longer wavelength when compared with the native one, and it seems possible that the modification of histidine and cysteine residues by superoxide radicals causes the conformational change of the enzyme and the consequent loss of catalytic activity.
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PMID:Inactivation of 3 alpha-hydroxysteroid dehydrogenase by superoxide radicals. Modification of histidine and cysteine residues causes the conformational change. 300 70

Quercetin is an equally good inhibitor of xanthine oxidase (type O, oxygen-reducing enzyme) and xanthine dehydrogenase (type D, NAD+-reducing enzyme) activity of a preparation of the xanthine-oxidizing enzyme partially purified from rat liver. The inhibition seems competitive with the oxidase form and non-competitive (mixed-type) with the dehydrogenase form of the enzyme. These inhibitory properties should be referred to the flavonoid structure of quercetin rather than to its antioxidant power. The antioxidant properties of quercetin and its inhibitory effect on the xanthine-oxidizing enzyme are discussed with reference to hyperuricemic and ischemic states.
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PMID:Inhibitory action of quercetin on xanthine oxidase and xanthine dehydrogenase activity. 386 71

The metabolic causes for immune impairment in patients with severe chronic inflammatory diseases have not been clearly defined. Recently, the overproduction of poly(ADP-ribose) in resting lymphocytes with unrepaired DNA strand breaks has been suggested to contribute to immune dysfunction in adenosine deaminase-deficient patients. Our experiments have determined to what extent DNA damage and poly(ADP-ribose) synthesis might also explain the impaired mitogen responsiveness of PBL exposed to toxic oxygen species. Treatment of normal resting human lymphocytes with xanthine oxidase and hypoxanthine dose-dependently induced DNA strand breaks and triggered the rapid synthesis of poly(ADP-ribose). Subsequently, NAD+ and ATP pools decreased precipitously. Lymphocytes exposed previously to the enzymatic oxidizing system did not synthesize DNA after stimulation with PHA. However, if the medium was supplemented with 3-aminobenzamide or nicotinamide, two compounds that inhibit poly(ADP-ribose) formation, cellular NAD+ and ATP pools were preserved, and the lymphocytes responded vigorously to a mitogenic challenge. Excessive poly(ADP-ribose) synthesis, provoked by DNA strand breakage, may represent a common pathway that connects the immunodeficiency syndromes associated with (a) exposure of lymphocytes to toxic oxygen species during chronic inflammatory states, (b) adenosine deaminase deficiency, and (c) certain DNA repair disorders.
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PMID:Lymphocyte dysfunction after DNA damage by toxic oxygen species. A model of immunodeficiency. 395 May 45

The absorption of xanthine oxidase into the bloodstream was studied in rabbits given a milk/cream preparation, fortified with 130 U bovine milk xanthine oxidase or the milk/cream preparation alone (control). The preparations were injected trans-abdominally into the intestines. The rise of plasma xanthine oxidase/dehydrogenase activity was studied with a radioenzymatic assay with and without NAD+. In rabbits, which received the fortified mixture, the plasma xanthine oxidase increase in 8 h was six times more than the increase in control animals (P less than 0.001). In both groups plasma xanthine dehydrogenase activity increased 3-4 times (P less than 0.001), without a significant difference between the two groups. We estimate that only 0.003%, or about 3 micrograms, of the xanthine oxidase added, is absorbed as an active enzyme from the intestine.
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PMID:Xanthine oxidase in rabbit plasma after application of a bovine milk preparation to small intestine. 608 54

Xanthine oxidase activity: O2-dependent and NAD+-dependent forms, were carried out in cytosol supernatant of Rat liver homogenat with adjuvant and hepatocytes induced arthritis and hepatitis. Both forms were increased without modification of their ratio. These results suggest that xanthine oxidase was implicated in the inflammatory reaction.
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PMID:[Xanthine oxidase activity: O2-dependent and NAD+-dependent forms in the liver, in rats with adjuvant arthritis and hepatitis]. 640 92

Xanthine oxidase activity: NAD+-dependent form (D) and O2-dependent form (O) were carried out in cytosol supernatants of connective tissue growth (T.C.N.F.), skin tail, liver and plasma of carrageenan induced granuloma in the Rat. The specific activities of skin, liver and plasma were normal in animals with a granuloma. The total specific activity (D + O): 7.53 +/- 0.98 mU/mg protein, and the percentage of form O: 51.6 +/- 5.1 of the granulomatous tissue as compared to the tail are significantly increased. These results suggest the likely function of xanthine oxidase during the inflammatory response.
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PMID:[Xanthine oxidase activity: NAD+-dependent and O2-dependent forms in carrageenan granuloma in the rat]. 642 8

Xanthine dehydrogenase was purified from soybean nodules and the kinetic properties were studied at pH 7.5. Km values of 5.0 +/- 0.6 and 12.5 +/- 2.5 microM were obtained for xanthine and NAD+, respectively. The pattern of substrate dependence suggested a Ping-Pong mechanism. Reaction with hypoxanthine gave Km's of 52 +/- 3 and 20 +/- 2.5 microM for hypoxanthine and NAD+, respectively. The Vmax for this reaction was twice that for the xanthine-dependent reaction. The pH dependence of Vmax gave a pKa of 7.6 +/- 0.1 for either xanthine or hypoxanthine oxidation. In addition the Km for xanthine had a pKa of 7.5 consistent with the protonated form of xanthine being the true substrate. Km for hypoxanthine varied only 2.5-fold between pH 6 and 10.7. Product inhibition studies were carried out with urate and NADH. Both products gave mixed inhibition with respect to both substrates. Xanthine dehydrogenase was able to use APAD+ as an electron acceptor for xanthine oxidation, with a Km at pH 7.5 of 21.2 +/- 2.5 microM and Vmax the same as that obtained with NAD+. Reduction of APAD+ by NADH was also catalyzed by xanthine dehydrogenase with a Km of 102 +/- 15 microM; Vmax was approximately 2.5 times that for the xanthine-dependent reaction, and was independent of pH between 6 and 9. Reaction with group-specific reagents indicated the possibility of an essential histidyl group. A thiol-modifying reagent did not cause inactivation of the enzyme. A role for the histidyl side chain in catalysis is proposed.
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PMID:Soybean nodule xanthine dehydrogenase: a kinetic study. 657 70


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