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 role of sulfhydryls in the protection of human polymorphonuclear neutrophils against extracellular oxidant attack was investigated by simultaneously exposing polymorphonuclear neutrophils to the thiol-oxidizing agent diamide and the oxidant-generating system xanthine-xanthine oxidase. Neither diamide nor the oxidants generated by the xanthine-xanthine oxidase system alone impaired the burst in chemiluminescence, hexose monophosphate shunt activity or formate oxidation normally seen during polymorphonuclear neutrophil phagocytosis. Incubation of the polymorphonuclear neutrophils simultaneously with diamide and xanthine-xanthine oxidase markedly impaired polymorphonuclear neutrophil phagocytosis, hexose monophosphate shunt activity, chemiluminescence and formate oxidation. Although the polymorphonuclear neutrophils exposed to diamide and xanthine-xanthine oxidase did not respond to a variety of phagocytizable stimuli, trypan blue exclusion was normal and hexose monophosphate shunt activity could be stimulated by diamide. The damaging effect of the diamide xanthine-xamthine oxidase system could be blocked by the addition of superoxide dismutase or catalase, but not by hydroxyl radical or singlet oxygen scavengers. We hypothesize that an unidentified population of thiols may play a role in protecting the polymorphonuclear neutrophil from endogenously derived oxidants.
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PMID:The effect of oxidant stress on diamide-treated human granulocytes. 46 44

Xanthine dehydrogenase engaged in catalyzing the oxidation of substrate by oxygen is repidly inactivated by the hydrogen peroxide generated during the reaction. Experimental evidence shows that peroxide reacts more readily with the reduced than with the oxidized form of the enzyme. Inactivation results from modification of the cyanolysable sulfur present at the molybdenum center.
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PMID:Syncatalytic modification of chicken liver xanthine dehydrogenase by hydrogen peroxide. The nature of the reaction. 47 63

1. All available N-mono- and N,N'-dimethylallopurinols and the corresponding 4-thioxo derivatives have been tested as substrates or inhibitors of bovine milk xanthine oxidase (xanthine: oxygen oxidoreductase, EC 1.2.3.2). 2. None of the compounds tested revealed any inhibitory activity towards the enzyme. 3. All compounds were resistant to enzymic oxidation, with the exception of 7-methylallopurinol and its 4-thioxo analog. Both these compounds were attacked at position 6. 7-Methylallopurinol was oxidised nearly ten times faster than the isomeric 3-methylhypoxanthine. 4. These observations can be explained by assuming that for attack at C-6, the enzyme must bind both to N-1 and N-2 in the pyrazole ring and causes tautomerisation, which places a double bond at position 5,6 in the pyrimidine ring. This activation process resembles the activation of hypoxanthine.
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PMID:Behavior of N-methylated allopurinols and related 4-thioxopyrazolo [3,4-d]pyrimidines towards bovine milk xanthine oxidase. 48 4

The capacity of three populations of mouse peritoneal macrophages to generate oxidative metabolites (as judged by extracellular release of H2O2) was compared to their ability to influence the intracellular fate of virulent Toxoplasma gondii. Macrophages from normal mice released little H2O2 and allowed unrestricted multiplication of intracellular toxoplasmas. Cells from chronically infected, immune (IM) mice released 4 times more H2O2 and displayed microbistatic activity. In contrast, macrophages from immune-boosted (IB) mice released 25 times more H2O2 than normal cells and rapidly killed the bulk of ingested toxoplasmas within 1 h. When macrophage monolayers were exposed to scavengers of O2-, H2O2, OH., and 1O2, both the inhibition of intracellular toxoplasma multiplication by IM macrophages and the killing of toxoplasmas by IB macrophages were reversed. Depriving cells of glucose, which markedly reduced H2O2 release, resulted in similar reversal of IM and IB macrophage anti-toxoplasma activity. As judged by the effect of the individual oxygen intermediate scavengers, O2- and H2O2 appeared to serve as precursors for the key toxic agents which may include OH. and 1O2. Providing normal macrophages with an exogenous source of oxidative metabolites generated by xanthine and xanthine oxidase, but not glucose and glucose oxidase, resulted in inhibition of intracellular toxoplasma growth. These findings suggest the presence of an oxygen-dependent antimicrobial system in mononuclear phagocytes beyond the production of O2- and H2O2, and indicate an important role for oxygen intermediates in macrophage resistance to the intracellular pathogen T. gondii.
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PMID:Macrophage oxygen-dependent antimicrobial activity. II. The role of oxygen intermediates. 51 87

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

To investigate the possibility that human polymorphonuclear leukocytes (PMN) elaborate sufficient amounts of hydrogen peroxide (H2O2) and other radicals of reduced oxygen to be autotoxic and retard directed cell movement and phagocytosis, the rate of ingestion of opsonized lipopolysaccharide-paraffin oil particles and movement through Nuclepore filters were studied. Ingestion rates were increased under anaerobic conditions and in normal aerobic conditions in the presence of extracellular catalase but not superoxide dismutase (SOD) or scavengers of singlet oxygen or hydroxyl radicals. Conversely, ingestion rates were decreased when cells were exposed to H2O2 or a superoxide anion (O2-)-H2O2 generating system of xanthine-xanthine oxidase. Catalase, but not SOD, prevented the effect and also enhanced the directed movement of PMN in normal aerobic conditions. PMN from volunteers administered 1600 U/day of the membrane lipid antioxidant alpha-tocopherol were hyperphagocytic but killed Staphylococcus aureus 502A less effectively than controls, suggesting that less H2O2 was available to damage PMN or kill bacteria. H2O2-dependent stimulation of the hexose monophosphate shunt, H2O2 release from phaogytizing PMN, and fluoresceinated concanavalin A cap formation promoted by H2O2 damage to microtubules were all diminished, but the release of O2- from phagocytizing PMN was not diminished in the vitamin E group. These results support the hypothesis that directed movement and phagocytosis by PMN are attenuated by autooxidative damage to the cell membrane by endogenously derived H2O2 and that the administration in vivo of vitamin E may prevent this damage by scavenging H2O2.
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PMID:Autooxidation as a basis for altered function by polymorphonuclear leukocytes. 87 28

The addition of imipramine to a suspension of resting polymorphonuclear leukocytes (PMNs) resulted in the generation of chemiluminescence (CL) (100,000 cpm with 1 X 10(-4)M imipramine). In the presence of a particle (zymosan) capable of activating the PMNs to generate reactive oxygen species, the magnitude of CL observed with 1 X 10(4)M imipramine was greatly enhanced (greater than 1,000,000 cpm). No CL was detected upon the addition of imipramine to PMNs isolated from a chronic granulomatous child or to alveolar macrophages isolated from rats. Another tricyclic antidepressant, amitriptyline, failed to generate CL with PMNs either alone or in the presence of zymosan; however, both imipramine and amitriptyline generated CL upon addition to the xanthine oxidase-purine superoxide generating system. Although the mechanism by which this drug-cell interaction results in the generation of CL is not known, the observations are suggestive that the CL may originate, in part, from the activation of imipramine by some reactive oxygen state(s).
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PMID:Chemiluminescence resulting from an interaction between imipramine and human polymorphonuclear leukocytes. 92 61

Part of the catalytic function of xanthine oxidase (XO) involves the transfer of two electrons from a substrate to a molybdenum ion on the enzyme followed by equilibration of these electrons among other electron resting sites on the enzyme. The electrons are removed from the enzyme at a flavin by oxygen to form hydrogen peroxide. This paper considers mechanisms which allow the electrons to equilibrate between the different resting sites on the enzyme. The mechanisms are chosen to be consistent with known properties of the enzyme (relative reduction potentials, electron transfer rates, and the estimated separation of these resting sites). Tunneling appears to be a good candidate to account for most of the electron transport. It is shown that the XO electron transport system is similar in many respects to sections of mitochondrial electron transport chains and can serve as a nice model for parts of these more complicated biological electron transport systems.
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PMID:Electron transport in xanthine oxidase. A model for other biological electron transport chains. 93 32

Granulocytes engaged in the phagocytosis of opsonized zymosan emit light by a process that is inhibited by superoxide dismutase and catalase. In the present report is is shown that light emission is the result of reactions between certain unspecified constituents of the ingested particles and some or all of the oxidizing agents (H2O2, O2),and possibly the hydroxyl radical and singlet oxygen) produced by the activated cells. This conclusion is based on a study of light emission by both activated cells ans artificial O2 generating system containing xanthine oxidase and purine. With these two systems light production required the presence of both zymosan and oxidizing agent, suggesting that the oxidation of particle components is necessary for luminescence to occur. The characteristics of the emission spectrum as well as the finding that granulocytes activated by a nonparticulate agent (F-) fail to liminesce show that light emission by the relaxation of singlet oxygen to the ground state does not contribute in a major way to the chemiluminescence of phagocytosing granulocytes; whether singlet oxygen contributes to chemiluminescence in other ways cannot be decided from the data available. Inasmuch as the oxidation of constituents of ingested particles is an important bacterial killing mechanism in the granulocyte, chemiluminescence may be viewed as a manifestation of the microbicidal activity of the cell.
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PMID:The origin of the chemiluminescence of phagocytosing granulocytes. 96 86

Incubation of either Staphylococcus epidermidis or Escherichia coli with a sufficiently high concentration of xanthine oxidase, an enzyme capable of reducing oxygen to superoxide (O2-), resulted in the death of the microorganisms. Protection against the killing os S. epidermidis by xanthine oxidase was afforded by superoxide dismutase, an enzyme which converts O2- to O2 and H2O2, and also by catalase, which destroys H2O2. These findings indicate that neither O2- nor H2O2 were able to kill S. epidermidis under the experimental conditions, but that the bactericidal agent was the product of a reaction between O2- and H2O2. By contrast, E. coli was protected by catalase but not by superoxide dismutase. With this organism, therefore, H2O2 appears to have been the bactericidal agent.
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PMID:Biological defense mechanisms. Evidence for the participation of superoxide in bacterial killing by xanthine oxidase. 108 40


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