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)

Crude cell-free extracts of nine strains of Streptomyces tested for nitroalkane-oxidizing activity showed production of nitrous acid from 2-nitropropane, 1-nitropropane, nitroethane, nitromethane, and 3-nitropropionic acid. These substrates were utilized in most strains but to a decreasing extent in the order given, and different strains varied in their relative efficiency of oxidation. p-Nitrobenzoic acid, p-aminobenzoic acid, enteromycin, and omega-nitro-l-arginine were not attacked. d-Amino acid oxidase, glucose oxidase, glutathione S-transferase, and xanthine oxidase, enzymes potentially responsible for the observed oxidations in crude cellfree extracts, were present at concentrations too low to play any significant role. A nitroalkane-oxidizing enzyme from streptozotocin-producing Streptomyces achromogenes subsp. streptozoticus was partially purified and characterized. It catalyzes the oxidative denitrification of 2-nitropropane as follows: 2CH(3)CH(NO(2))CH(3) + O(2) --> 2CH(3)COCH(3) + 2HNO(2). At the optimum pH of 7.5 of the enzyme, 2-nitropropane was as good a substrate as its sodium salt; t-nitrobutane was not a substrate. Whereas Tiron, oxine, and nitroxyl radical acted as potent inhibitors of this enzyme, superoxide dismutase was essentially without effect. Sodium peroxide abolished a lag phase in the progress curve of the enzyme and afforded stimulation, whereas sodium superoxide did not affect the reaction. Reducing agents, such as glutathione, reduced nicotinamide adenine dinucleotide, and nicotinamide adenine dinucleotide phosphate, reduced form, as well as thiol compounds, were strongly inhibitory, but cyanide had no effect. The S. achromogenes enzyme at the present stage of purification is similar in many respects to the enzyme 2-nitropropane dioxygenase from Hansenula mrakii. The possible involvement of the nitroalkane-oxidizing enzyme in the biosynthesis of antibiotics that contain a nitrogen-nitrogen bond is discussed.
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PMID:Nitroalkane oxidation by streptomycetes. 3 65

The degradation of DNA by bleomycin was studied in the absence and in the presence of added reducing agents, including 2-mercaptoethanol, dithiothreitol, reduced nicotinamide adenine dinucleotide phosphate, H2O2, and ascorbate, and in the presence of a superoxide anion generating system consisting of xanthine oxidase and hypoxanthine. In all cases, breakage of DNA was inhibited by low concentrations of chelators; where examined in detail, deferoxamine mesylate was considerably more potent than (ethylenedinitrilo)tetraacetic acid. Iron was found to be present in significant quantities in all reaction mixtures. Thus, the pattern of inhibition observed is attributed to the involvement of contaminating iron in the degradation of DNA by bleomycin. Cu(II), Zn(II), and Co(II) inhibit degradation of DNA by bleomycin and Fe(II) in the absence of added reducing agents. A model is proposed in which the degradation of DNA in these systems is dependent on the oxidation of an Fe(II)-bleomycin-DNA complex.
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PMID:Effect of chelating agents and metal ions on the degradation of DNA by bleomycin. 8 Feb 26

Arthrobacter S-2, originally isolated by enrichment on xanthine, produced high levels of xanthine oxidase activity, requiring as little as a 20-fold purification to approach homogeneity with some preparations. Molecular oxygen, ferricyanide, and 2,6-dichlorophenol-indophenol served as electron acceptors, but nicotinamide adenine dinucleotide did not. The enzyme was relatively specific when compared with previously studied xanthine-oxidizing enzymes, but at least one purine was observed to be oxidized at each of the three positions of the purine ring that have been subject to oxidation by this type of enzyme. The enzyme had a relatively high Km for xanthine (1.3 X 10(-4) M), and substrate inhibition was not observed with this compound, in contrast to the enzyme from cow's milk. In fact, an opposite effect was observed, and double-reciprocal plots with xanthine as the variable substrate showed a concave downward deviation at high concentrations. At 2.5 mM xanthine the enzyme had a specific activity approximately 50 times that of the most active preparations of the milk enzyme. The spectrum of the Arthrobacter enzyme resembled that of milk xanthine oxidase, suggesting a similarity of the prosthetic centers of the two enzymes. The bacterial enzyme was relatively small and may be dimeric, with approximate native and subunit molecular weights of 146,000 and 79,000, respectively.
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PMID:Bacterial xanthine oxidase from Arthrobacter S-2. 68 Dec 79

The nitrovasodilator, nicorandil, is a clinically effective antianginal agent. We tested whether nicorandil may also possess anti-free-radical characteristics, since the nicotinamide moiety of its molecular structure is a known hydroxyl radical scavenger. In vitro production of hydroxyl radicals by hypoxanthine plus xanthine oxidase in the presence of iron produced a marked degradation of deoxyribose. Nicorandil and the structural analogs, nicotinic acid and nicotinamide, produced significant inhibition of deoxyribose breakdown at concentrations equipotent to the classical hydroxyl radical scavenger, mannitol. Nicorandil also produced a concentration-dependent inhibition of superoxide anion production by canine neutrophils that were activated with either phorbol myristate acetate (PMA) or opsonized zymosan. This inhibition could not be mimicked by the analog, nicotinamide. While equimolar concentrations of nitroglycerin produced less inhibition of superoxide anion generation in opsonized zymosan-activated neutrophils than that observed with nicorandil, nitroglycerin did not alter free-radical production in PMA-stimulated neutrophils. Glyburide, the ATP-sensitive potassium-channel blocker, did not reverse the action of nicorandil on neutrophils. Thus, nicorandil is a uniquely different nitrovasodilator with anti-free-radical and neutrophil-modulating properties.
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PMID:Anti-free-radical and neutrophil-modulating properties of the nitrovasodilator, nicorandil. 132 63

Peroxisomes are subcellular respiratory organelles which contain catalase and H2O2-producing flavin oxidases as basic enzymatic constituents. These organelles have an essentially oxidative type of metabolism and have the potential to carry out different important metabolic pathways. In recent years the presence of different types of superoxide dismutase (SOD) have been demonstrated in peroxisomes from several plant species, and more recently the occurrence of SOD has been extended to peroxisomes from human and transformed yeast cells. A copper,zinc-containing SOD from plant peroxisomes has been purified and partially characterized. The production of hydroxyl and superoxide radicals has been studied in peroxisomes. There are two sites of O2- production in peroxisomes: (1) in the matrix, the generating system being xanthine oxidase; and (2) in peroxisomal membranes, dependent on reduced nicotinamide adenine dinucleotide (NADH), and the electron transport components of the peroxisomal membrane are possibly responsible. The generation of oxygen radicals in peroxisomes could have important effects on cellular metabolism. Diverse cellular implications of oxyradical metabolism in peroxisomes are discussed in relation to phenomena such as cell injury, peroxisomal genetic diseases, peroxisome proliferation and oxidative stress, metal and salt stress, catabolism of nucleic acids, senescence, and plant pathogenic processes.
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PMID:Metabolism of oxygen radicals in peroxisomes and cellular implications. 133 30

There are two types of collagenases, products of two distinct genes, called MMP-1 (matrix metalloproteinase 1 or "fibroblast-type collagenase") and MMP-8 ("neutrophil collagenase"). In synovial fluid, MMP-8 is stored as latent proenzyme in polymorphonuclear neutrophils. MMP-8 is activated by hypochlorous acid produced by myeloperoxidase from hydrogen peroxide and chloride ion and by the hydroxyl radical produced in Haber Weiss reaction fed by superoxide produced by, eg, NADPH (reduced nicotinamide adenine dinucleotide) oxidase and xanthine oxidase. In addition to activation upon secretion, oxidatively modified MMP-8 is susceptible to a subsequent proteolytic attack and activation by cathepsin G. The authors suggest that activation of neutrophil-derived MMP-8 involves oxidative, nonproteolytic activation upon secretion and a more slowly progressive proteolytic activation by cathepsin G (or chymases and tryptases), and that these oxidative and proteolytic activation mechanisms act in concert. In contrast to MMP-8, MMP-1 is synthesized de novo and secreted immediately after synthesis by fibroblasts, macrophages, and some epithelial cells. Human rheumatoid synovial tissue contains mainly fibroblast-type MMP-1 collagenase as assessed by collagenase extracted from synovial tissue and by MMP-1 and MMP-8 immunostaining. It is suggested that in vivo, MMP-1 in synovitis tissue is activated by a plasminogen activator/plasminogen/prostromelysin (alternatively tryptases)/proMMP-1 cascade. In conclusion, MMP-8 and MMP-1 show type-specific compartmentalization and modes of activation in rheumatoid synovial fluid and tissue.
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PMID:Collagenase in synovitis of rheumatoid arthritis. 141 81

The endothelium-associated enzyme xanthine oxidase is known to generate reactive oxygen intermediates which may damage the surrounding tissue. We investigated whether reactive oxygen intermediates released by xanthine oxidase exert a toxic effect on isolated rat islet cells. The xanthine oxidase (25 mU/ml)/hypoxanthine (0.5 mmol/l) system released reactive oxygen intermediates in vitro as detected by luminol in a chemiluminescence analysing system. The addition of nicotinamide inhibited the release of reactive oxygen intermediates in a dose-dependent manner (50% inhibition at 20 mmol/l). Exposure of islet cells to enzyme generated reactive oxygen intermediates caused lysis of 39% of the cells within 15 h. Monitoring the mitochondrial function of islet cells by the conversion of tetrazolium bromide to its formazan product revealed a significant reduction of the respiratory activity down to 51% of that of the controls by 30 min after the initiation of the xanthine oxidase reaction. Mitochondrial dysfunction preceded plasma membrane damage. The addition of nicotinamide, a radical scavenger and inhibitor of the DNA repair enzyme poly(ADP-ribose) synthetase protected the islet cells from lysis and partially preserved their mitochondrial activity in the presence of reactive oxygen intermediates. We conclude that activation of the endothelial enzyme xanthine oxidase, known to be induced by mediators of immune cells or by episodes of ischaemia and reperfusion causes islet cell damage with subsequent cell death in early phases of pancreatic islet cell destruction.
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PMID:Oxygen radicals generated by the enzyme xanthine oxidase lyse rat pancreatic islet cells in vitro. 147 12

Effects of non-steroidal anti-inflammatory drugs (NSAID: amfenac sodium, diclofenac sodium, indomethacin and ketoprofen) on the generation of superoxide anion (O2-) by isolated rat polymorphonuclear leukocytes (PMN) were studied spectrophotometrically using cytochrome c. The effects of these drugs were also studied on O2- production by the xanthine-xanthine oxidase and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-NADPH oxidase systems. Amfenac sodium, at 0.1 mM, inhibited significantly O2- generation in rat PMN induced by opsonized zymosan. At 0.5 mM, diclofenac sodium and indomethacin inhibited the O2- generation in rat PMN. All of the above drugs slightly inhibited O2- production by the xanthine-xanthine oxidase system. On the other hand, O2- production by the NADPH-NADPH oxidase system was significantly inhibited by the addition of amfenac sodium, ketoprofen or indomethacin. These results suggest that non-steroidal anti-inflammatory drugs do not work as an O2- scavenger and block O2- production by the NADPH-NADPH oxidase system of rat PMN. It is concluded that amfenac sodium and the other drugs are able to inhibit granulocyte O2- production by blocking the activation of NADPH-oxidase.
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PMID:Inhibitory effects of non-steroidal anti-inflammatory drugs on superoxide generation. 165 19

Reductive metabolism of the hair dye constituent, nitro-p-phenylenediamine (2-nitro-1,4-diaminobenzene, NPDA), and its acetylated metabolite, NPDA N4-acetate, was investigated with rat liver subcellular fractions, microsomes and cytosol. Under anaerobic conditions, these compounds were reduced to their corresponding amines by these fractions. The microsomal nitro-reducing activity was retarded completely by air and strongly by carbon monoxide. Reduced nicotinamide adenine dinucleotide phosphate (NADPH) functioned more effectively than reduced nicotinamide adenine dinucleotide (NADH) as an electron donor in the microsomal reduction of the nitro compounds, and flavin mononucleotide (FMN) gave rise to a marked enhancement in the microsomal activity, especially when added to an anaerobic incubation mixture containing both NADH and NADPH. The cytosolic nitro-reducing activity was attributed to xanthine oxidase, aldehyde oxidase and other unknown enzyme(s), based on the results of cofactor requirements and inhibition experiments.
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PMID:Reductive metabolism of nitro-p-phenylenediamine by rat liver. 204 1

The formation of oxygen-derived free radicals in cerebral ischaemia has been implicated in altering the BBB permeability, cause oedema and tissue damage. However little attention has been paid regarding the involvement of xanthine oxidase in the cerebral ischaemic events. Recently we demonstrated that cerebral ischaemia promotes the conversion of xanthine oxidase type D (nicotinamide adenine dinucleotide-dependent dehydrogenase) to type 0 (oxygen-dependent superoxide-producing oxidase). This investigation was concerned with elucidating the relationship between the conversion of xanthide oxidase and the duration of brain ischaemia. Four vessel-occlusion served as a model for the induction of cerebral ischaemia in rats. Xanthine oxidase was assayed by high pressure liquid chromatography using ultraviolet and electrochemical detection. The enzymatic conversion of xanthine oxidase from type D to type O increased with time from 7.6-15% during 5 min ischaemia to 27% and 36% at 15 min and 30 min after ischaemia, respectively. These results support the contention that xanthine oxidase may participate in free radical-induced ischaemic brain oedema.
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PMID:Ischaemic brain oedema and xanthine-xanthine oxidase system. 208 93


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