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 reactions of native bovine catalase with superoxide and solvated electrons have been investigated using three different methods for generation of these reducing substrates: gamma-radiolysis of oxygenated or deaerated buffer solutions in the presence of an OH radical scavenger; either xanthine or acetaldehyde with xanthine oxidase; and low-temperature (77 K) gamma-radiolysis of buffered ethylene glycol/water solutions with subsequent annealing of samples at 183 K. The first spectral evidence for catalase compound II formation from native catalase via reaction with superoxide was obtained. The results are compared with results for peroxidase compound II or III formation observed under the same experimental conditions. A scheme is proposed to explain these observations involving intermediate formation of catalase compounds I and III and the ferrous enzyme. The one-electron reduction of catalase and peroxidase by radiolytically-generated solvated electrons was compared. In the present study the first absorption spectrum of a high-spin ferrous catalase which has peaks at 561 and 594 nm is reported, in comparison with a hemochromogen low-spin ferrous peroxidase observed under the same experimental conditions (peaks at 527 and 556 nm). Both spectra were recorded at 77 K. Data presented in this work also provide the first spectral evidence indicating the low temperature (183 K) conversion of high-spin ferrous catalase into compound III (oxycatalase) in the presence of dioxygen. Under the same experimental conditions low-spin ferrous peroxidase was converted into the high-spin ferrous form without oxyperoxidase formation.
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PMID:Spectral studies of intermediate species formed in one-electron reactions of bovine liver catalase at room and low temperatures. A comparison with peroxidase reactions. 136 11

Free radical generation and the mobilization of catalytic iron are important in the pathogenesis of alcohol-induced liver injury. Cimetidine is a free radical scavenger in thermal skin injury and cobra venom-induced lung injury, and was therefore investigated as a scavenger of ethanol-induced free radicals. In vitro cimetidine inhibited iron-mediated cleavage of DNA as well as the potentiation of such cleavage by bleomycin. Peroxidation of microsomes by xanthine-xanthine oxidase, acetaldehyde-xanthine oxidase, as well as by the addition of low-molecular weight iron chelates were inhibited (17-100%) by cimetidine (0.1-1 mM). Free radical generation due to ethanol in isolated rat hepatocytes was studied by measuring ethane and pentane production. Cimetidine (1 mM) significantly decreased ethane and pentane production due to ethanol: 1 mM (2.2 +/- 0.3 vs. 1.0 +/- 0.2 pmol ethane per 10(6) cells/h; p less than 0.01, 4.2 +/- 0.4 versus 1.6 +/- 0.3 pmole per 10(6) cells/h pentane; p less than 0.001). Similar inhibitions were observed in the isolated perfused liver. Studies of superoxide reduction of ferricytochrome-C as well as hydroxyl radical generation by Fe(+)+/EDTA/ascorbate revealed that cimetidine was an effective hydroxyl radical scavenger. In summary, in a variety of in vitro systems, as well as in isolated hepatocytes and perfused liver, cimetidine inhibits ethanol-induced free radical injury. These findings may warrant its investigation as a therapeutic agent.
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PMID:Cimetidine as a scavenger of ethanol-induced free radicals. 141 59

Xanthine dehydrogenase (XDH) from the unicellular green alga Chlamydomonas reinhardtii has been purified to electrophoretic homogeneity by a procedure which includes several conventional steps (gel filtration, anion exchange chromatography and preparative gel electrophoresis). The purified protein exhibited a specific activity of 5.7 units/mg protein (turnover number = 1.9 .10(3) min-1) and a remarkable instability at room temperature. Spectral properties were identical to those reported for other xanthine-oxidizing enzymes with absorption maxima in the 420-450 nm region and a shoulder at 556 nm characteristic of molybdoflavoproteins containing iron-sulfur centers. Chlamydomonas XDH was irreversibly inactivated upon incubation of enzyme with its physiological electron donors xanthine and hypoxanthine, in the absence of NAD+, its physiological electron acceptor. As deduced from spectral changes in the 400-500 nm region, xanthine addition provoked enzyme reduction which was followed by inactivation. This irreversible inactivation also took place either under anaerobic conditions or whenever oxygen or any of its derivatives were excluded. Adenine, 8-azaxanthine and acetaldehyde which could act as reducing substrates of XDH were also able to inactivate it upon incubation. The same inactivating effect was observed with NADH and NADPH, electron donors for the diaphorase activity associated with xanthine dehydrogenase. In addition, partial activities of XDH were differently affected by xanthine incubation. We conclude that xanthine dehydrogenase inactivation by substrate is due to an irreversible process affecting mainly molybdenum center and that sequential and uninterrupted electron flow from xanthine to NAD+ is essential to maintain the enzyme in its active form.
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PMID:Purification and substrate inactivation of xanthine dehydrogenase from Chlamydomonas reinhardtii. 152 76

Free radical generation and catalytic iron have been implicated in the pathogenesis of alcohol-induced liver injury but the source of free radicals is a subject of controversy. The mechanism of ethanol-induced liver injury was investigated in isolated hepatocytes from a rodent model of iron loading in which free radical generation was measured by the determination of alkane production (ethane and pentane). Iron loading (125 mg/kg i.p.) increased hepatic non-heme iron 3-fold, increased the prooxidant activity of cytosolic ultrafiltrates 2-fold and doubled ethanol-induced alkane production. The addition of desferrioxamine (20 microM), a tight chelator of iron, completely abolished alkane production indicating the importance of catalytic iron. The role of cellular oxidases as a source of ethanol induced free radicals was studied through the use of selective inhibitors. In both the presence and absence of iron loading, selective inhibition of xanthine oxidase with oxipurinol(20 microM) diminished ethanol-induced alkane production 0-40%, inhibition of aldehyde oxidase with menadione (20 microM) diminished alkane production 36-75%, while the inhibition of aldehyde and xanthine oxidase by feeding tungstate (100 mg/kg/day) virtually abolished alkane production. Addition of acetaldehyde(50 microM) to hepatocytes generated alkanes at rates comparable to those achieved with ethanol indicating the importance of acetaldehyde metabolism in free radical generation. The cellular oxidases (aldehyde and xanthine oxidase) along with catalytic iron play a fundamental role in the pathogenesis of free radical injury due to ethanol.
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PMID:The role of cellular oxidases and catalytic iron in the pathogenesis of ethanol-induced liver injury. 160 88

The production of hydrogen peroxide was measured by following the oxidation of dichlorofluorescein (DCFH) entrapped into platelets. Resting platelets produced nanomolar quantities of DCF, which was proportional to the concentration of platelets and was steady during 1 h of incubation. A significant increase of basal DCF fluorescence was induced by stimuli namely thrombin, arachidonic acid, the Ca2+ ionophore A23187 and PMA. The effect of agonists has been also measured in the presence of 3-amino-1,2,4-triazole (AT) or N-ethylmaleimide (NEM), inhibitors of catalase and glutathione peroxidase, respectively. A further significant enhancement of DCF produced in stimulated platelets was detected only in the presence of NEM. A correlation was found between the increase in DCF and externally added hydrogen peroxide or the oxidizing species formed by xanthine oxidase plus acetaldehyde. The yield was not affected by superoxide dismutase and was higher in the presence of AT or NEM. A cooperative effect in the presence of both inhibitors was shown. Glutathione peroxidase plus glutathione diminished the level of DCF to basal levels.
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PMID:Generation of hydrogen peroxide in resting and activated platelets. 162 82

We investigated the binding of highly purified soluble human C-reactive protein (CRP) to human neutrophils. Binding of CRP to neutrophils was rapid (50% of maximal binding occurred within 15 seconds), and complete within 5 minutes. Binding was inhibitable by excess unlabeled CRP, and nonspecific binding in the presence of a 200-fold excess of unlabeled CRP was 10% of total binding. Binding was not affected by other proteins, including albumin, fibronectin, rabbit IgG, or normal human plasma. Maximal binding required both calcium (0.5 mM) and magnesium (0.24 mM) ions. Calcium phosphorylcholine (10 micrograms/ml) or sodium citrate (10 micrograms/ml) completely dissociated bound CRP. Binding was saturable and most consistent with a 2-site model, demonstrating both a high-affinity receptor (1.4 x 10(4) sites/cell; Kd 3.7 x 10(-10) M) and a low-affinity receptor (4.2 x 10(5) sites/cell; Kd 2.5 x 10(-8) M). CRP at concentrations of 50 micrograms/ml inhibited the neutrophil superoxide production induced by phorbol ester. At concentrations of 100 micrograms/ml or greater, CRP also inhibited superoxide production in a cell-free xanthine oxidase-acetaldehyde system. These data suggest that CRP can down-regulate neutrophil oxidative capacity through interaction with receptors on neutrophils as well as by direct antioxidant activity.
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PMID:Binding of C-reactive protein to human neutrophils. Inhibition of respiratory burst activity. 165 Feb 22

The therapy of copper poisoning with mercaptodextran inhibits the copper-induced haemolysis, whereas 2,3- dimercaptopropanesulfonic acid (DMPS) may accelerate such haemolysis. Some aspects of the mechanisms of these effects were investigated. The possible generation of activated oxygen species during the interaction of Cu++ and chelating thiols was studied using a chemoluminiscent method detecting oxygen radicals. It was found that incubation of DMPS with copper ions or erythrocyte membranes was accompanied by generation of oxygen radicals. Mercaptodextran added to similar suspensions did not lead to oxygen radical production. And unlike DMPS, mercaptodextran acted as a scavenger of radicals generated by the xanthine oxidase/acetaldehyde system. The different ability of the chelating thiols to cope with free radicals may explain their different potentials to protect against copper-induced haemolysis. Our results also indicate that mercaptodextran may be a useful therapeutic agent in cases of haemolytic crisis in Wilson's disease.
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PMID:Mercaptodextran--a new copper chelator and scavenger of oxygen radicals. 171 13

NAD(P)-linked aldehyde dehydrogenases catalyze the oxidation of a wide variety of aldehydes. Thirteen of these enzymes have been identified in mouse tissues; eleven are found in the liver. Some are substrate-nonspecific; others are relatively substrate-specific. The present investigation sought to determine which of these enzymes are operative in catalyzing the oxidation of retinaldehyde to retinoic acid, a metabolite of vitamin A that promotes the differentiation of epithelial and other cells. Spectrophotometric and HPLC assays were used for this purpose. Enzyme-catalyzed oxidation of retinaldehyde (25 microM) was restricted to the cytosol (105,000 g supernatant fraction) and occurred at a rate of 211 nmol/min/g liver; oxidation of acetaldehyde (4 mM) by this fraction proceeds about ten times faster. At least 90% of this activity was NAD dependent. Of the approximately 10% that was apparently NAD independent, two-thirds was inhibited by 1 mM pyridoxal, a known inhibitor of aldehyde oxidase. Of the six cytosolic aldehyde dehydrogenases, only two, viz. AHD-2 and AHD-7, catalyzed the oxidation of retinaldehyde to retinoic acid. An additional NAD-dependent enzyme, viz. xanthine oxidase (dehydrogenase form), also catalyzed the reaction. Catalysis by AHD-2 accounted for more than 90% of the total NAD-dependent activity. Km values were 0.7, 0.6 and 0.9 microM, respectively, for the AHD-2-, AHD-7- and xanthine oxidase (dehydrogenase form)-catalyzed reaction. AHD-4, an aldehyde dehydrogenase found in the cytosol of mouse stomach epithelium and cornea, did not catalyze the reaction.
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PMID:Identification of mouse liver aldehyde dehydrogenases that catalyze the oxidation of retinaldehyde to retinoic acid. 188 36

The susceptibility of rat mast-cell heparin to oxidative degradation was examined. Heparin as a component of intact mast-cell granules (MCG) was degraded following ingestion by normal human neutrophils. In contrast, neutrophils from patients with chronic granulomatous disease (CGD), which do not respond to stimulation with respiratory-burst activity, exhibited a greatly diminished ability to degrade phagocytosed MCG heparin. MCG-associated heparin also was cleaved by H2O2 plus Fe2+ (Fenton's reagent). Isolated heparin proteoglycan (average Mr approx. 750,000) was rapidly cleaved to smaller molecules similar in size to commercial pig heparin upon exposure to Fenton's reagent. This cleavage was inhibited by catalase and by the hydroxyl-radical (OH.)-scavenger mannitol, but not by superoxide dismutase (SOD). The cleavage products retained approx. 26% of the anticoagulant activity of the native molecule. The heparin proteoglycan was also cleaved by acetaldehyde/xanthine oxidase/FeSO4, a system that generates superoxide (O2.-), H2O2 and OH.. Whereas the cleavage at relatively high iron ion concentrations was inhibited by catalase and mannitol but not by SOD, at lower iron ion concentrations the cleavage was inhibited by catalase, mannitol and SOD. These findings suggest the involvement of OH., which at high Fe2+ concentrations is generated by Fenton's reagent (H2O2 plus Fe2+), and at low iron ion concentrations is generated by the iron-ion-catalysed interaction between O2.- and H2O2 (Haber-Weiss reaction). These studies suggest that oxygen radicals generated by activated phagocytes may contribute to the degradation in vivo of both solubilized and granule-associated proteoglycan heparin.
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PMID:Oxidative degradation of rat mast-cell heparin proteoglycan. 217 84

To investigate a possible role of free radical production by xanthine oxidase in the pathogenesis of ethanol-induced hepatic lipid peroxidation, chow-fed rats were given ethanol (5 g/kg) and placed at 32 degrees C for 6 h, which resulted in increased hepatic malondialdehyde levels. Pretreatment with allopurinol in amounts that effectively inhibited xanthine metabolism also significantly decreased ethanol-induced lipid peroxidation, suggesting participation of free radicals produced by xanthine oxidase in the peroxidative process. Both acetaldehyde and purine can serve as substrates for xanthine oxidase. Pretreatment with cyanamide increased hepatic acetaldehyde levels 5-fold, yet this was associated with a decrease in lipid peroxidation, indicating that acetaldehyde is not the xanthine oxidase substrate involved. By contrast, ethanol increased hepatic contents of hypoxanthine and xanthine and enhanced urinary output of allantoin (a final product of xanthine metabolism), incriminating increased metabolism of purines. Ethanol administration also enhanced hepatic nicotinamide adenine dinucleotide (reduced form). A corresponding rise of nicotinamide adenine dinucleotide (reduced form) in vitro inhibited xanthine dehydrogenase activity by 60%-76%. Increased purine degradation, possibly associated with a shift from the dehydrogenase to the xanthine oxidase pathway (secondary to nicotinamide adenine dinucleotide [reduced form]-mediated inhibition of xanthine dehydrogenase activity) is proposed as a possible mechanism for ethanol-stimulated free radical production. Because allopurinol attenuates the associated lipid peroxidation, this agent might be considered for possible therapeutic use in alcohol-induced liver damage.
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PMID:Role of xanthine oxidase in ethanol-induced lipid peroxidation in rats. 229 79


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