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 formation and decay of intermediate compounds of horseradish peroxidase, lactoperoxidase, and myeloperoxidase formed in the presence of the superoxide/hydrogen peroxide-generating xanthine/xanthine oxidase system has been studied by observation of spectral changes in both the Soret and visible spectral regions and both on millisecond and second time scales. It is tentatively concluded that in all cases compound III is formed in a two-step reaction of native enzyme with superoxide. The presence of superoxide dismutase completely inhibited compound III formation; the presence of catalase had no effect on the process. Spectral data which indicate differences in the decay of horseradish peroxidase compound III back to the native state in comparison with compounds III of lactoperoxidase and myeloperoxidase are also presented.
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PMID:The reactions of horseradish peroxidase, lactoperoxidase, and myeloperoxidase with enzymatically generated superoxide. 254 42

Oxidation of the reactive site methionine (Met) in alpha-1-proteinase inhibitor (alpha-1-PI) to methionine sulfoxide (Met(O] is known to cause depletion of its elastase inhibitory activity. To estimate the selectivity of different oxidants in converting Met to Met(O) in alpha-1-PI, we measured the molar ratio Met(O)/alpha-1-PI at total inactivation. This ratio was determined to be 1.2 for both the myeloperoxidase/H2O2/chloride system and the related compound NH2Cl. With taurine monochloramine, another myeloperoxidase-related oxidant, 1.05 mol Met(O) were generated per mol alpha-1-PI during inactivation. These oxidants attack preferentially one Met residue in alpha-1-PI, which is identical with Met 358, as concluded from the parallelism of loss of elastase inhibitory activity and oxidation of Met. A similar high specificity for Met oxidation was determined for the xanthine oxidase-derived oxidants. In contrast, the ratio found for ozone and m-chloroperoxybenzoic acid was 6.0 and 5.0, respectively, indicating oxidation of additional Met residues besides the relative site Met in alpha-1-PI, i.e. unselective action of these oxidants. Further studies were performed on the efficiency of oxidants for total depletion of the elastase inhibitory capacity of alpha-1-PI. Ozone and m-chloroperoxybenzoic acid were 10-fold less effective and the superoxide anion/hydroxyl radicals were 30-50-fold less effective to inactivate the elastase inhibitory activity as compared to the myeloperoxidase-derived oxidants. The myeloperoxidase-related oxidants are discussed as important regulators of alpha-1-PI activity in vivo.
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PMID:Different selectivities of oxidants during oxidation of methionine residues in the alpha-1-proteinase inhibitor. 254 97

Stimulated neutrophils discharge large quantities of superoxide (O2.-), which dismutates to form H2O2. In combination with Cl-, H2O2 is converted into the potent oxidant hypochlorous acid (HOCl) by the haem enzyme myeloperoxidase. We have used an H2O2 electrode to monitor H2O2 uptake by myeloperoxidase, and have shown that in the presence of Cl- this accurately represents production of HOCl. Monochlorodimedon, which is routinely used to assay production of HOCl, inhibited H2O2 uptake by 95%. This result confirms that monochlorodimedon inhibits myeloperoxidase, and that the monochlorodimedon assay grossly underestimates the activity of myeloperoxidase. With 10 microM-H2O2 and 100 mM-Cl-, myeloperoxidase had a neutral pH optimum. Increasing the H2O2 concentration to 100 microM lowered the pH optimum to pH 6.5. Above the pH optimum there was a burst of H2O2 uptake that rapidly declined due to accumulation of Compound II. High concentrations of H2O2 inhibited myeloperoxidase and promoted the formation of Compound II. These effects of H2O2 were decreased at higher concentrations of Cl-. We propose that H2O2 competes with Cl- for Compound I and reduces it to Compound II, thereby inhibiting myeloperoxidase. Above pH 6.5, O2.- generated by xanthine oxidase and acetaldehyde prevented H2O2 from inhibiting myeloperoxidase, increasing the initial rate of H2O2 uptake. O2.- allowed myeloperoxidase to function optimally with 100 microM-H2O2 at pH 7.0. This occurred because, as previously demonstrated, O2.- prevents Compound II from accumulating by reducing it to ferric myeloperoxidase. In contrast, at pH 6.0, where Compound II did not accumulate, O2.- retarded the uptake of H2O2. We propose that by generating O2.- neutrophils prevent H2O2 and other one-electron donors from inhibiting myeloperoxidase, and ensure that this enzyme functions optimally at neutral pH.
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PMID:Influence of superoxide on myeloperoxidase kinetics measured with a hydrogen peroxide electrode. 255 13

This study was designed to determine whether oxygen-derived free radicals play a role in the pathogenesis of gastric lesions produced by hemorrhagic shock in the rat. Allopurinol (Zyloric), an inhibitor of xanthine oxidase (responsible for the formation of superoxide radicals) and MTDQ-DA (Kontrad), a synthetic antioxidant of dihydroquinoline type were used. In the anesthetized rat 0.1 N HCl was instilled into the stomach and the rat was bled to reduce the blood pressure to 30 mmHg for 20 min. The blood shed was retransfused. Twenty min later the stomach was removed. The area of gastric mucosal lesions were measured, the activity of endogenous peroxidase was examined histochemically and a histological grading was made. Both allopurinol and MTDQ-DA significantly protected against hemorrhagic shock-induced gastric lesions and peroxidation. These results suggest that oxygen-derived free radicals play an important role in the formation of gastric lesions produced by ischemia plus 0.1 N HCl.
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PMID:Role of oxygen-derived free radicals in hemorrhagic shock-induced gastric lesions of rats. 259 23

A selective and sensitive assay of substrates (hypoxanthine, xanthine and allopurinol) of xanthine oxidase by reversed-phase liquid chromatography coupled with the use of immobilized enzyme reactors is described. These compounds were oxidized by immobilized xanthine oxidase and produced hydrogen peroxide, which was determined fluorometrically using immobilized peroxidase and p-hydroxyphenylacetic acid. The detection limits of hypoxanthine, xanthine and allopurinol were approximately 50, 120 and 130 pg per injection, respectively. Immobilized xanthine oxidase inhibited by oxipurinol during the assay was reactivated by 2,6-dichlorophenolindophenol and could be used for a long period without a significant activity loss. These methods were applied to plasma and urine samples.
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PMID:Simultaneous assay of hypoxanthine, xanthine and allopurinol by high-performance liquid chromatography and activation of immobilized xanthine oxidase as an enzyme reactor. 260 92

Previous studies showed the beneficial effects of superoxide dismutase +/- catalase in perfusion-preserved rabbit kidneys but failed to show benefit in flush-cooled organs. The current studies undertook to evaluate scavengers, xanthine oxidase inhibitors, and agents that prevent the release of myeloperoxidase in 3 systems: kidneys preserved by perfusion or by flush cooling for 24 hr, studied immediately, and warm ischemia-injured kidneys evaluated after a 24-hr recovery period. In none of these groups could we demonstrate any protective effects against preservational or warm ischemic injury by the above modalities. Even though biochemical and other evidence from previous studies suggested free radical-induced injury to occur in preserved rabbit kidneys, these studies using renal function as the indicator did not do so.
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PMID:Lack of effect of oxygen-radical scavenging systems in the preserved reperfused rabbit kidney. 267 97

The pathogenesis of neonatal necrotizing enterocolitis is unknown, but a possible role for reactive oxygen metabolites has been postulated. We evaluated whether developmental differences exist in the levels of 1) the free radical-generating enzyme xanthine oxidase, 2) granulocyte peroxidase, an index of the resident granulocyte population, 3) free radical-scavenging enzymes (superoxide dismutase, catalase, and glutathione peroxidase), and 4) reduced glutathione, an endogenous antioxidant, in the ileal and colonic mucosa of 1-d-old, 3-d-old, 2-wk-old, and 1-mo-old piglets. We found no xanthine dehydrogenase/oxidase activity in 1-d to 1-mo-old piglets. Mucosal granulocyte peroxidase activity was higher in older animals, indicating that there was an age-dependent infiltration of granulocytes (eosinophils, neutrophils) in the distal bowel. The peroxidase activity per circulating granulocyte, however, did not vary with age. Superoxide dismutase activity was significantly higher in 1-d-old piglets than in all older age groups; glutathione peroxidase activity was significantly lower in 1-d-old animals than that of older age groups. There was no detectable catalase activity in the mucosa when tissue was corrected for catalase activity of blood. Finally, ileal GSH levels were significantly lower in 1-d-old than in 2-wk-old and 1-mo-old animals, whereas colonic reduced glutathione activity did not differ among age groups. In conclusion, the distal bowel of the neonatal piglet appears to have a limited capacity to generate oxidants via xanthine oxidase and resident granulocytes. However, the neonatal piglet intestine has a lower capacity to detoxify hydrogen peroxide than that of older animals.
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PMID:Developmental biology of oxidant-producing enzymes and antioxidants in the piglet intestine. 274 Jan 52

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

Desferrioxamine mesylate (Desferal), a transition metal ion chelator, has been used to inhibit the in vitro redox cycling of transition metal ions. ESR spectroscopy was utilized to detect and identify Desferal's one-electron oxidation product. We demonstrate that a horseradish peroxidase/H2O2 system, a xanthine oxidase/hypoxanthine system, and a hydroxyl radical-generating system are all capable of oxidizing Desferal to a nitroxide free radical. The same 9-line ESR spectrum (g = 2.0065, alpha N = 7.85 G, alpha H(2) = 6.35 G) was detected in all of the above systems. We, therefore, stress that care must be taken when using Desferal as a transition metal ion chelator to keep its concentration low enough to minimize these reactions, or to use a different metal ion chelator.
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PMID:The enzymatic oxidation of Desferal to a nitroxide free radical. 282 Aug 3

Listeria monocytogenes, a gram-positive motile bacterium which can cause severe bacterial infection in humans, is considered to be pathogenic by virtue of its ability to resist intracellular killing. Since the mechanism of intracellular survival is poorly understood, we assessed the sensitivity of L. monocytogenes to several potent antibacterial products. Phorbol myristate acetate (PMA)-stimulated polymorphonuclear cells (PMNs) produced extracellular antibacterial products which were inhibited completely by catalase, suggesting a role for oxidative agents in this process. L. monocytogenes in logarithmic (log) growth phase resisted PMA-stimulated PMN extracellular products significantly more than L. monocytogenes in stationary (stat) growth phase or Escherichia coli (three strains) in either phase of growth. The role of oxidative agents was studied further by using xanthine oxidase-xanthine, glucose oxidase-glucose, and myeloperoxidase enzyme systems to generate hydroxyl radical (.OH), hydrogen peroxide (H2O2), and hypochlorous acid (OCl-), respectively. L. monocytogenes in log phase resisted the antibacterial products of these enzyme systems under conditions which produced superoxide (O2-) and H2O2 at concentrations similar to those produced extracellularly by PMA-stimulated PMNs, while stat-growth-phase L. monocytogenes and E. coli in either phase of growth were susceptible. Antibacterial activity could be blocked or inhibited by exogenous catalase (for all oxygen radical-generating systems), mannitol, or desferoxamine (for xanthine oxidase-xanthine) and alanine (for myeloperoxidase), suggesting that .OH and OCl- were responsible for this activity. Log-phase L. monocytogenes had 2.5-fold higher bacteria-associated catalase activity, as compared with stat-phase L. monocytogenes. These experiments, therefore, suggest that log-phase L. monocytogenes resists oxidative antibacterial agents by producing sufficient catalase to inactivate these products. This may contribute to the ability of L. monocytogenes to survive intracellularly.
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PMID:Relationship of bacterial growth phase to killing of Listeria monocytogenes by oxidative agents generated by neutrophils and enzyme systems. 282 83


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