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)

Nitroaromatic compounds, which frequently contaminate the environment, are known to be reduced to corresponding aromatic amines by fish as well as mammals under anaerobic conditions. Although amine products are not generally formed aerobically, "nitroreductase"-mediated redox cycling of nitroaromatics may occur under these conditions, leading to enhanced production of a potentially toxic oxygen species, superoxide (O-2). In this study, we have investigated the ability of channel catfish (Ictalurus punctatus) hepatic microsomal and soluble fractions to stimulate O-2) production upon exposure to a model redox cycling nitroaromatic compound, nitrofurantoin (NF). Two assays for O-2 production, cytochrome c reduction and cyanide-insensitive oxygen consumption, were stimulated by NF exposure to both hepatic fractions. These reactions were partially inhibited by superoxide dismutase (SOD), and by SOD and catalase in the oxygen consumption assay, providing specific evidence for the involvement of O-2 in the stimulatory effect by NF. Furthermore, results of cofactor requirement and inhibition studies suggest that NF enhancement of O-2 production was mediated by NADPH-cytochrome P-450 (c) reductase in the microsomal fraction and xanthine oxidase in the soluble fraction. These findings comprehensively suggest that the in vitro stimulation of O-2 production by nitroaromatics as indicated in mammals may also occur in fish and, therefore, suggests a similar potential for oxyradical-mediated toxicities in these species.
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PMID:Nitrofurantoin-stimulated superoxide production by channel catfish (Ictalurus punctatus) hepatic microsomal and soluble fractions. 284 61

The objectives of this study were to describe the ultrastructure of granulocyte-Schistosoma mansoni egg interaction and to determine the role of reduced oxygen products as effectors of cell-mediated damage to the parasite target. Granulocytes attached to the parasites and closely applied their plasma membranes to the microspicules of the egg shell 30 min after mixing in the presence of immune serum. By 4 h, the egg shell was fractured and granulocyte pseudopodia extended toward the underlying miracidium. Granulocyte attachment to eggs resulted in release of O2- (0.30-0.52 nmol/min per 2 X 10(6) cells) and accumulation of H2O2 (0.14-0.15 nmol/min) in the presence of antibody or complement. Granulocytes reduced egg tricarboxylic-acid cycle activity and hatching by 28.3 +/- 0.9 and 35.2 +/- 2.8%, respectively (cell-egg ratio of 1,000: 1). Exogenous superoxide dismutase (10 micrograms/ml) inhibited granulocyte toxicity for egg metabolic activity (3.0 +/- 2.1% reduction in acetate metabolism vs. 28.3 +/- 0.9% decrease in controls without superoxide dismutase, P less than 0.0005) and hatching (12.5 +/- 1.8% reduction, P less than 0.0005), whereas catalase and heparin had no effect. Inhibitors of myeloperoxidase (1 mM azide, cyanide, and methimazole) augmented granulocyte-mediated toxicity of egg tricarboxylic-acid cycle activity (44-58% reduction in activity vs. 31 and 35% reduction in controls), suggesting that H2O2 released from cells was degraded before reaching the target miracidium. Oxidants generated by acetaldehyde (2 mM)-xanthine oxidase (10 mU/ml) also decreased egg metabolic activity and hatching by 62.0 +/- 9.0 and 38.7 +/- 7.3%, respectively. Egg damage by the cell-free system was partially prevented by superoxide dismutase (26.5 +/- 4.2% reduction in egg tricarboxylic-acid activity) and completely blocked by catalase (0% reduction in activity). These data suggest that granulocyte-mediated toxicity for S. mansoni eggs is dependent on release of O2- or related molecules. These oxygen products, unlike H2O2, may readily reach the target miracidium where they may be converted to H2O2 or other microbicidal effector molecules.
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PMID:Role of granulocyte oxygen products in damage of Schistosoma mansoni eggs in vitro. 298 56

The selenium-containing glutathione peroxidase, when in its active reduced form, was inactivated during exposure to the xanthine oxidase reaction. Superoxide dismutase completely prevented this inactivation, whereas catalase, hydroxyl radical scavengers, or chelators did not, indicating that O2 was the responsible agent. Conversion of GSH peroxidase to its oxidized form, by exposure to hydroperoxides, rendered it insensitive toward O2. The oxidized enzyme regained susceptibility toward inactivation by O2 when reduced with GSH. The inactivation by O2 could be reversed by GSH; however, sequential exposure to O2 and then hydroperoxides caused irreversible inactivation. Reactivity toward CN- has been used as a measure of the oxidized form of GSH peroxidase, whereas reactivity toward iodoacetate has been taken as an indicator of the reduced form. By these criteria both O2 and hydroperoxides convert the reduced form to oxidized forms. A mechanism involving oxidation of the selenocysteine residue at the active site has been proposed to account for these observations.
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PMID:Inactivation of glutathione peroxidase by superoxide radical. 299 78

The ability of different homologues of Coenzyme Q to quench O2- was tested in vitro with three experimental systems known to generate O2-. Two of them were biological generators, namely the xanthine-xanthine oxidase system and the cyanide-insensitive NADPH oxidase of polymorphonuclear leucocytes. The third was a chemical generator of O2-, the NADH-phenazine methosulphate-nitroblue tetrazolium mixture. Short-side-chain ubiquinones were found to be the most potent scavengers of O2-, being effective at concentrations as low as 10(-7) M. This finding might be ascribed to the relatively greater water-solubility of the lower homologues of CoQ. We postulate that CoQ10 may well exert such an O2- -scavenging mechanisms in vivo where it is inserted in its natural phospholipid environment.
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PMID:In vitro effect of different ubiquinones on the scavenging of biologically generated O2-. 301 40

The superoxide radical O2.-, whether produced by the xanthine/xanthine oxidase reaction or infused as KO2, solubilized by a crown ether in dry dimethyl sulphoxide, initiated a free-radical chain oxidation of anionic 2-nitropropane. Superoxide dismutase, but not catalase, inhibited oxidation of the nitroalkane. Xanthine oxidase suffered a syncatalytic inactivation, during the co-oxidation of 2-nitropropane, which was reversed by dialysis. Cyanide exacerbated this syncatalytic inactivation and rendered it irreversible. The frequently observed oxidations of nitroalkanes by flavoenzymes now need to be re-examined to clarify the extent to which O2.--initiated free-radical chain oxidation contributed to the overall nitroalkane oxidation.
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PMID:Free-radical chain oxidation of 2-nitropropane initiated and propagated by superoxide. 302 20

Lipid peroxidation of brain lipids as determined by the conjugated diene method was observed in mice following administration of sublethal doses of potassium cyanide (KCN). Conjugated diene production was dose- and time-dependent; 10 mg/kg KCN produced detectable levels of conjugated dienes at 30 min post cyanide, whereas, 15 mg/kg produced marked levels of conjugated dienes over a 10-60-min period after KCN. Pretreatment of mice with either diltiazem (600 micrograms/kg, i.v.) or allopurinol (25 mg/kg, i.v.) blocked the generation of conjugated dienes. These results suggest lipid peroxidation of neuronal membranes play a role in cyanide intoxication and this action is related to altered regulation of neuronal calcium homeostasis and activation of xanthine oxidase.
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PMID:Peroxidation of brain lipids following cyanide intoxication in mice. 366 Apr 18

Two hereditary disorders of sulfur amino acid metabolism, beta-mercaptolactate-cysteine disulfideuria and sulfite oxidase deficiency, were described twenty years ago. Other examples of these disorders have been limited to about 5 of each in the world literature since then. Reasons for the apparent rarity of these conditions are discussed and the analytical procedures to identify them are reviewed. The detection of the first depends on the positive result of a cyanide-nitroprusside test followed by positive identification of the specific mixed disulfide. The enzyme mercaptopyruvate sulfur transferase has been shown to be deficient. In the second disorder of sulfite oxidase deficiency, the clinical presentation with progressive dystonia and dislocated lenses in an infant should suggest further laboratory investigations for this disorder which would not be detected by conventional laboratory screening procedures. Laboratory diagnosis can be obtained by use of the Merckoquant sulfite test on a fresh urine sample. Quantitative thiosulfate and taurine measurements can also be made. Positive identification of the specific amino acid S-sulfo-L-cysteine should also be made. The enzyme sulfite oxidase is missing from such organs as liver, kidney and brain. This latter condition may also be associated with xanthinuria. For this combined disorder of sulfite oxidase and xanthine oxidase, a deficiency of a molybdenum-containing cofactor has been demonstrated.
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PMID:A review of the clinical presentation and laboratory findings in two uncommon hereditary disorders of sulfur amino acid metabolism, beta-mercaptolactate cysteine disulfideuria and sulfite oxidase deficiency. 388 41

1. Turkey liver xanthine dehydrogenase engaged in catalysing the oxidation of xanthine by dichlorophenol-indophenol was progressively inactivated by methanol. This inactivation was reversible by NAD(+). 2. Reaction with arsenite and with cyanide, in each case first-order with respect to enzyme, resulted in characteristic alterations in the visible absorption spectrum of the enzyme. The rate of spectral change on reaction with either agent paralleled the rate of loss of enzyme activity. 3. Cyanide inactivation was accompanied by elimination from the enzyme of sulphur as thiocyanate. Partial restoration of activity was effected by incubation with sulphide or with selenide. The results suggest that turkey liver xanthine dehydrogenase, like milk xanthine oxidase (Massey & Edmonson, 1970), contains at the active centre a cyanolysable persulphide group essential to catalytic activity and that selenium may replace sulphur in this group to give an active enzyme. 4. Incubation of the native enzyme with sulphide or with selenide resulted in the rapid loss of half of the xanthine-oxidizing activity, apparently by disrupting the molybdenum and (Fe/S)II loci. This may indicate non-equivalence of the intramolecular electron-transfer systems.
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PMID:Turkey liver xanthine dehydrogenase. Reactivation of the cyanide-inactivated enxyme by sulphide and by selenide. 446 58

The reduced forms of xanthine oxidase, xanthine dehydrogenase, aldehyde oxidase, and sulfite oxidase are inactivated by cyanide. Following gel filtration to remove excess of reductant and cyanide, the isolated enzymes remain inactive. Thiocyanate, a product of inactivation of the oxidized forms of the xanthine- and aldehyde-oxidizing enzymes by cyanide, is not released during inactivation of the reduced enzymes. Studies with [14C]cyanide show that, while stoichiometric binding is required for the onset of inactivation, its continued binding is not essential to maintenance of the inactivated state. Electron paramagnetic resonance and absorption spectroscopic studies on the isolated inactivated enzymes show that prosthetic groups other than molybdenum are fully oxidized but that the molybdenum centers are modified. Reactivation is accomplished by incubation with suitable oxidants. Aerobic reactivation of inactive sulfite oxidase required only 1 eq of ferricyanide/active site. However, under rigorously anaerobic conditions, 3 to 4 mol of ferricyanide/active site were reduced, indicating that the molybdenum centers in the inactive enzyme had been reduced below the levels attained by the native enzyme during catalysis.
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PMID:Mechanisms of inactivation of molybdoenzymes by cyanide. 624 90

In previous studies, we noted that Candida hyphae and pseudohyphae could be damaged and probably killed by neutrophils, primarily by oxygen-dependent nonphagocytic mechanisms. In extending these studies, amount of damage to hyphae again was measured by inhibition of [(14)C]cytosine uptake. Neutrophils from only one of four patients with chronic granulomatous disease damaged hyphae at all, and neutrophils from this single patient damaged hyphae far less efficiently than simultaneously tested neutrophils from normal control subjects. Neutrophils from neither of two subjects with hereditary myeloperoxidase deficiency damaged the hyphae. This confirmed the importance of oxidative mechanisms in general and myeloperoxidase-mediated systems in particular in damaging Candida hyphae. Several potentially fungicidal oxidative intermediates are produced by metabolic pathways of normal neutrophils, but their relative toxicity for Candida hyphae was previously unknown. To help determine this, cell-free in vitro systems were used to generate these potentially microbicidal products. Myeloperoxidase with hydrogen peroxide, iodide, and chloride resulted in 91.2% damage to hyphal inocula in 11 experiments. There was less damage when either chloride or iodide was omitted, and no damage when myeloperoxidase was omitted or inactivated by heating. Azide, cyanide, and catalase (but not heated catalase) inhibited the damage. Systems for generation of hydrogen peroxide could replace reagent hydrogen peroxide in the myeloperoxidase system. These included glucose oxidase, in the presence of glucose, and xanthine oxidase, in the presence of either hypoxanthine or acetaldehyde. In the presence of myeloperoxidase and a halide, the toxicity of the xanthine oxidase system was not inhibited by superoxide dismutase and, under some conditions, was marginally increased by this enzyme. This suggested that superoxide radical did not damage hyphae directly but served primarily as an intermediate in the production of hydrogen peroxide. The possible damage to hyphae by singlet oxygen was examined using photoactivation of rose bengal. This dye damaged hyphae in the presence of light and oxygen. The effect was almost completely inhibited by putative quenchers of singlet oxygen: histidine, tryptophan, and 1,4-diazobicyclo[2.2.2]octane. These agents also inhibited damage to hyphae by myeloperoxidase, halide, and either hydrogen peroxide or a peroxide source (xanthine oxidase plus acetaldehyde). Myeloperoxidase-mediated damage to hyphae was also inhibited by dimethyl sulfoxide, an antioxidant and scavenger of the hydroxyl radical. These data support the involvement of oxidative mechanisms and the myeloperoxidase-H(2)O(2)-halide system, in particular in damaging hyphae in vitro and perhaps in vivo as well.
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PMID:Damage to Candida albicans hyphae and pseudohyphae by the myeloperoxidase system and oxidative products of neutrophil metabolism in vitro. 625 27


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