Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Superoxide anion, a highly reactive free radical, was generated in vitro using enriched purified xanthine oxidase. Collagen solutions exposed to superoxide radical failed to gel normally when heated to 37 degrees C. The magnitude of the inhibition of gelation was propotional to duration of exposure and to flux of superoxide. Since inhibition of collagen gelation reflects alteration of collagen biochemistry, and/or collagen degradation, it is suggested that the action of free radicals produced in vivo by leukocytes may adversely affect the structural or functional integrity of cartilage and adjacent joint structures.
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PMID:Inhibition of collagen gelation by action of the superoxide radical. 21 93

On the basis of the work of Gutteridge, Tanner & Bray [Biochem. J. (1978) 175, 887-897] and of other data in the literature, a mechanism for the reaction of xanthine oxidase with reducing substrates is proposed. In the Michaelis complex, xanthine is bound to molybdenum via the N-9 nitrogen atom. Coupled transfer of two electrons to molybdenum and the C-8 proton to the enzyme yields (Enzyme)-Mo-SH. Concerted with this process, reaction of the xanthine residue with a nucleophile in the active centre yields a covalent intermediate that breaks down to give the product by alternative pathways at high and at low pH values.
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PMID:The mechanism of action of xanthine oxidase. The relationship between the rapid and very rapid molybdenum electron-paramagnetic-resonance signals. 21 62

An efficient scavenger for radiolytically generated hydroxyl (OH) radicals, p-nitrosodimethylaniline, was used to try to substantiate the presence of this oxygen radical species in several biochemical systems. Most of these systems which were investigated had previously been assumed to generate OH radicals, e.g. the autoxidation of 6-hydroxydopamine, the hydroxylating system NADH/phenazine methosulfate, and the oxidation of xanthine or acetaldehyde by xanthine oxidase. We did not observe inhibition of the bleaching of p-nitrosodimethylaniline in oxygenated solutions by other scavengers of OH radicals nor, in the case of xanthine/xanthine oxidase, by catalase and superoxide dismutase. We therefore conclude that, under biochemical conditions as opposed to radiolysis or photolysis, no freely diffusable OH radicals are formed. Rather, a strongly oxidizing OH-analogous complex is considered to represent the p-nitrosodimethylaniline-detectable species formed under these conditions.
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PMID:On the nature of biochemically generated hydroxyl radicals. Studies using the bleaching of p-nitrosodimethylaniline as a direct assay method. 22 Dec 20

Membrane (Na +K)ATPase isolated from rat brain was preincubated in a medium in which superoxide radicals were generated enzymatically. Exposure to superoxide radicals caused an irreversible inactivation, which could be prevented by further addition of superoxide dismutase. (Na + K)ATPase was also protected by addition of allopurinol, a xanthine oxidase inhibitor, during preincubation. The K-activated nitrophenylphosphatase associated with (Na + K)ATPase was also found to be inactivated by preincubation with superoxide radicals, which could be prevented by superoxide dismutase.
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PMID:Effects of superoxide radicals on transport (Na + K) adenosine triphosphatase and protection by superoxide dismutase. 22 49

Two proteins (P1 and P2, with weights of 57,500 and 27,500 respectively) were isolated from Euglena gracilis. Both proteins show cyanide-insensitive superoxide dismutase activity in the "classical" superoxide dismutase assay, using xanthine-xanthine oxidase as O2.- generator. If O2.- is generated chemically (autoxidation of reduced anthraquinone), photochemically (illuminated riboflavine) or pulse radiolytically, only protein P1 but not P2 shows SOD activity. Protein P1 contains 1 g atom (determined: 0.82) iron (no Mn or Cu) per mole protein and may thus be defined as iron-superoxide dismutase. Protein P2, showing the spectral properties of a flavoprotein, exhibits the activities of ferredoxin-NADP-oxidoreductase and "diaphorase". The cyanide-insensitive SOD-activity of this Diaphorase" in the xanthine oxidase-assay for superoxide dismutase makes this classical and commonly used test unreliable for assay cyanide insensitive SOD activities. The existence of the "prokaryote-type" of superoxide dismutase (Fe-SOD) in Euglena gracilis is exceptional for an eukaryotic, autotrophically grown organisms.
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PMID:Cyanide insensitive iron superoxide dismutase in Euglena gracilis. Comparison of the reliabilities of different test systems for superoxide dismutases. 22 43

Myeloperoxidase (MPO), H2O2 and a halide form a powerful antimicrobial system effective against bacteria, fungi, viruses and mammalian cells. After phagocytosis, MPO is released into the phagosome from adjacent granules where it interacts with H2O2 generated either by leukocytic or microbial metabolism and a halide such as chloride or iodide to form agents toxic to the ingested organisms. Evidence for H2O2 and MPO participation in the microbicidal activity of polymorphonuclear leukocytes (PMNs) has been obtained from patients with neutrophil dysfunction. In chronic granulomatous disease, PMNs have a microbicidal defect associated with the absence of the respiratory burst. The importance of H2O2 deficiency in the PMN dysfunction is emphasized by its reversal by H2O2. PMNs which lack MPO also have a major fungicidal and bactericidal defect. Bactericidal activity is particularly low during the early postphagocytic period, after which the organisms are killed. Although emphasizing the importance of MPO-mediated antimicrobial systems particularly during the early postphagocytic period, these findings also indicate the presence of MPO-independent systems which develop slowly but are ultimately effective. The MPO-independent antimicrobial systems may be oxygen-dependent or oxygen-independent. The acetaldehyde-xanthine oxidase system has been used as a model of the MPO-independent, oxygen-dependent antimicrobial systems of the PMN. A microbicidal effect by this system was observed which was inhibited by superoxide dismutase, catalase and scavengers of hydroxyl radicals (OH') and singlet oxygen (1O2). The microbicidal activity of acetaldehyde and xanthine oxidase is increased considerably by MPO and chloride. The formation of ethylene from methional or 2-oxo-4-methylthiobutyric acid by PMNs has been regarded as evidence for OH' formation. We have found ethylene formation to be largely dependent on MPO and evidence for the initiation of ethylene formation by 1O2 has been obtained. Both the xanthine oxidase system and the MPO-H2O2-halide system convert diphenylfuran into cis-dibenzoylethylene, an effect which is compatible with, although not proof of, the formation of 1O2 by these systems.
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PMID:The role of myeloperoxidase in the microbicidal activity of polymorphonuclear leukocytes. 22 42

A spectrophotometric method for the determination of three forms of xanthine oxidoreductase, namely dehydrogenase (D), dehydrogenase-oxidase (D/O) and oxidase (O), is described. Enzymic fractions obtained from rat liver were found to contain either all three forms, or (under special conditions of preparation) only two forms, D and D/O. The conversion of form D leads to form D/O leads to form O in the presence of Cu2+ ions was shown. Form D/O acted with NAD+ as well as with O2 as electron acceptors, it exhibited greater affinity to NAD+ than to O2, and NAD+ abolished the oxidase activity of this form. Moreover, oxidase activity of form D/O was inhibited by NADH. These facts indicate that NAD+ and O2 compete for the same active site on the enzyme molecule.
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PMID:Intermediate dehydrogenase-oxidase form of xanthine oxidoreductase in rat liver. 22 81

Xanthine oxidase suffers autoinactivation in the course of catalyzing the oxidation of acetaldehyde. When no special efforts were made to maintain a high pO2 in these reaction mixtures catalase protected the xanthine oxidase, but superoxide dismutase did not. However, when oxygen depletion was slowed or prevented by working at lower concentrations of xanthine oxidase, at lower temperatures or by vigorous agitation under an atmosphere of 100% oxygen, superoxide dismutase or catalase protected markedly when added separately and protected almost completely when added together. This result correlates with the greater production of O2-, relative to H2O2, by xanthine oxidase, at elevated pO2. Since histidine also provided some protection and the high levels of acetaldehyde used would have precluded any significant effect of OH., we conclude that singlet oxygen, or something with similar reactivity, was generated from O2- plus H2O2 and contributed significantly to the observed autoinactivation.
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PMID:Autoinactivation of xanthine oxidase: the role of superoxide radical and hydrogen peroxide. 22 31

In the presence of Fe-3+ and complexing anions, the peroxidation of unsaturated liver microsomal lipid in both intact microsomes and in a model system containing extracted microsomal lipid can be promoted by either NADPH and NADPH : cytochrome c reductase or by xanthine and xanthine oxidase. Erythrocuprein effectively inhibits the activity promoted by xanthine and xanthine oxidase but produces much less inhibition of NADPH-dependent peroxidation. The singlet-oxygen trapping agent, 1, 3-diphenylisobenzofuran, had no effect on NADPH-dependent peroxidation but strongly inhibited the peroxidation promoted by xanthine and xanthine oxidase. NADPH-dependent lipid peroxidation was also shown to be unaffected by hydroxyl radical scavengers.. The addition of catalase had no effect on NADPH-dependent lipid peroxidation, but it significantly increased the rate of malondialdehyde formation in the reaction promoted by xanthine and xanthine oxidase. The results demonstrate that NADPH-dependent lipid peroxidation is promoted by a reaction mechanism which does not involve either superoxide, singlet oxygen, HOOH, or the hydroxyl radical. It is concluded that NADPH-dependent lipid peroxidation is initiated by the reduction of Fe-3+ followed by the decomposition of hydroperoxides to generate alkoxyl radicals. The initiation reaction may involve some form of the perferryl ion or other metal ion species generated during oxidation of Fe-2+ by oxygen.
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PMID:The mechanism of liver microsomal lipid peroxidation. 23 6

Indoleamine 2,3-dioxygenase purified to apparent homogeneity from rabbit intestine was inhibited by scavengers for superoxide anion such as superoxide dismutase and 1,2-dihydroxybenzene-3,5-disulfonic acid (Tiron). On the other hand, beta-carotene and 1,4-diazobicyclo-(2,2,2)-octane, scavengers for singlet oxygen, did not affect the enzyme activity significantly. The degree of inhibition of the dioxygenase by superoxide dismutase preparations from bovine erythrocytes, green peas, spinach leaves, and Escherichia coli paralleled that observed with these dismutase preparations on the aerobic reduction of cytochrome c by xanthine oxidase and its substrate. The pH profiles of the inhibition by dismutase of the dioxygenase and cytochrome c reduction were also similar and the maximal inhibition was observed around pH 10 in both cases. The degree of inhibition was not affected by the concentration of substrate but was a function of the concentration of dismutase. It was inversely related to the concentrations of the dioxygenase and its cofactors, ascorbic acid and methylene blue, both of which were required for maximum activity. Ascorbic acid could be replaced either by xanthine oxidase and its substrate, or by tetrabutylammonium superoxide prepared by electrolytic reduction of molecular oxygen, or by potassium superoxide. When limited amounts of superoxide anion were added to the reaction mixture containing a substrate amount of the dioxygenase, the ratio of the amount of superoxide anion added to that of the product formed was approximately unity both under aerobic and anaerobic conditions. Taken together, these findings indicate that superoxide anion, rather than molecular oxygen, is utilized as substrate by indoleamine 2,3-dioxygenase.
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PMID:Studies on indoleamine 2,3-dioxygenase. I. Superoxide anion as substrate. 23 93


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