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)

Vanadate or molybdate strongly accelerate the cooxidation of NADH, or of reduced nicotinamide mononucleotide, by the xanthine oxidase plus xanthine reaction. Superoxide dismutase eliminated the effect of vanadate or molybdate, while catalase was without effect. It follows that vanadate or molybdate accelerate the oxidation of dihydropyridines by O-2. A stoichiometry of 4 NADH oxidized per O-2 introduced suggests a chain reaction for which a mechanism is proposed. These results provide an explanation for the reported stimulation, by vanadate, of NADH oxidation by biological membranes.
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PMID:Vanadate and molybdate stimulate the oxidation of NADH by superoxide radical. 608 31

Cell-free extracts of Lactobacillus plantarum contain non-proteinaceous compounds which mimic superoxide dismutase activity. Using the test system in which O-2 is generated by xanthine oxidase, superoxide dismutase activity is found in cell-free extracts, where proteins are removed by precipitation. This activity is strongly decreased after dialysis of cell-free extracts. Superoxide dismutase activity was also investigated by means of pulse radiolysis. Cell-free extracts of Escherichia coli were also investigated as a comparison, which were known to contain superoxide dismutase. With cell-free extracts of both L. plantarum and E. coli the decay of O-2 was markedly increased. However, the type of reaction of the O-2 decay was of first order in the presence of E. coli extracts due to superoxide dismutase(s), and of second order in the presence of L. plantarum extracts, indicating that O-2 elimination is not an enzymic reaction. Mn2+ phosphate(s) might be responsible for the observed elimination of O-2. The production of O-2 is not detectable during NADH-, lactate- or pyruvate oxidase reactions in L. plantarum extracts.
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PMID:Oxygen utilization by Lactobacillus plantarum. II. Superoxide and superoxide dismutation. 624 45

Carbon monoxide:methylene blue oxidoreductase, the key enzyme of CO-oxidation in energy metabolism of the carboxydobacterium Pseudomonas carboxydovorans, has been isolated in good yield and purity and found to contain FAD, molybdenum, iron, and labile sulfide in the ratio of 1:1:4:4. The enzyme is, therefore, a new molybdenum-containing iron-sulfur flavoprotein, exhibiting chemical and spectral properties quite similar to those of xanthine oxidase. Analytical data on the spectral characteristics of the enzyme in the oxidized and various reduced states are presented. Carbon monoxide:methylene blue oxidoreductase turned out to be photoreducible in the presence of EDTA and urea and was subject to reoxidation by air oxygen; no flavoprotein semiquinone was formed. Unphysiological electron acceptors, e.g. methylene blue, were used as oxidizing substrates whereas NAD or NADP turned out to be ineffective. Methylene blue reduction with CO was not affected by the presence of allopurinol, and carbon monoxide:methylene blue oxidoreductase was not able to catalyze the reduction of methylene blue with xanthine, adenine, or aldehydes. CO was the only reducing substrate used by the enzyme. Carbon monoxide:methylene blue oxidoreductase formed no sulfite adduct, and the reactivity with ferricyanide or cytochrome c was significant but slow. As known for other molybdenum hydroxylases, carbon monoxide:methylene blue oxidoreductase was rapidly inactivated by methanol, but the enzyme exhibited no ability to catalyze the oxidation of NADH with methylene blue, and NAD was not able to overcome methanol inhibition.
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PMID:Chemical and spectral properties of carbon monoxide: methylene blue oxidoreductase. The molybdenum-containing iron-sulfur flavoprotein from Pseudomonas carboxydovorans. 627 81

DNA degradation by a copper(II)-phenanthroline complex was studied in the presence of NADH, 2-mercaptoethanol or a mixture of hypoxanthine and xanthine oxidase, which generates the superoxide radical, O2-. In all cases degradation was prevented by catalase but not by scavengers of the hydroxyl radical, OH. It remains possible, however, that OH was generated in close association with DNA so that the scavengers could not remove it before it reacted. Superoxide dismutase inhibited DNA degradation at low copper (II) phenanthroline concentrations in the presence of NADH or hypoxanthine-xanthine oxidase, but not at higher complex concentrations. Superoxide dismutase had little effect on DNA degradation in the presence of 2-mercaptoethanol. The role of oxygen radicals in the DNA degradation induced by copper(II) phenanthroline is discussed.
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PMID:The role of the superoxide and hydroxyl radicals in the degradation of DNA and deoxyribose induced by a copper-phenanthroline complex. 629 45

When heart or liver mitochondria are exposed to superoxide radicals generated from xanthine + xanthine oxidase their ability to take up and to retain Ca2+ is impaired. The rate of oxidation of pyruvate + malate as substrates is diminished and the appearance of thiol groups when the mitochondria are supplied with these substrates is abolished. These inhibitory effects are offset if respiration is supported by succinate in presence of rotenone provided that a substrate (beta-hydroxybutyrate) is provided to maintain the reduction of NADH. The data agree with the thesis that a generation of thiol groups is essential to maintain membrane integrity and that the generation depends on provision of reduced NAD(P)H.
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PMID:The effect of superoxide generation on the ability of mitochondria to take up and retain Ca2+. 629 91

This investigation examined the effect of the anthracycline antitumor agents on reactive oxygen metabolism in rat heart. Oxygen radical production by doxorubicin, daunorubicin, and various anthracycline analogues was determined in heart homogenate, sarcoplasmic reticulum, mitochondria, and cytosol, the major sites of cardiac damage by the anthracycline drugs. Superoxide production in heart sarcosomes was significantly increased by anthracycline treatment; for doxorubicin, the reaction appeared to follow saturation kinetics with an apparent Km of 112.62 microM, required NADPH as cofactor, was accompanied by the accumulation of hydrogen peroxide, and probably resulted from the transfer of electrons to molecular oxygen by the doxorubicin semiquinone after reduction of the drug by sarcosomal NADPH:cytochrome P-450 reductase (NADPH:ferricytochrome oxidoreductase, EC 1.6.2.4). Superoxide formation was also significantly enhanced by the anthracycline antibiotics in the mitochondrial fraction. Doxorubicin stimulated mitochondrial superoxide formation in a dose-dependent manner that also appeared to follow saturation kinetics (apparent Km of 454.55 microM); however, drug-related superoxide production by mitochondria required NADH rather than NADPH and was significantly increased in the presence of rotenone, which suggested that the proximal portion of the mitochondrial NADH dehydrogenase complex [NADH:(acceptor) oxidoreductase, EC 1.6.99.3] was responsible for the reduction of doxorubicin at this site. In heart cytosol, anthracycline-induced superoxide formation and oxygen consumption required NADH and were significantly reduced by allopurinol, a potent inhibitor of xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2). Reactive oxygen production was detected in all of our studies despite the presence of both superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and glutathione peroxidase (glutathione:hydrogen peroxide oxidoreductase, EC 1.11.1.9) in each cardiac fraction. These results suggest that free radical formation by the anthracycline antitumor agents, which occurs in the same myocardial compartments that are subject to drug-induced tissue injury, may damage the heart by exceeding the oxygen radical detoxifying capacity of cardiac mitochondria and sarcoplasmic reticulum.
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PMID:Effect of anthracycline antibiotics on oxygen radical formation in rat heart. 629 97

Free radicals and lipid peroxides have recently been identified by us [1, 2, 3] as metabolic intermediates during acute myocardial ischemia. The mechanisms by which evolving myocardial ischemia initiates free radical production are not clear. Based on studies in vitro, it is feasible to consider the following possibilities: (a) dissociation of intramitochondrial electron support system and altered phospholipid integrity with inactivation of cytochrome oxidase, which results in release of ubisemiquinone, flavoprotein and superoxide radicals; (b) accumulation and increased release of intra/extracellular metabolites like NADH, lactate flavoproteins and catecholamines which react either with themselves or with O2 and ascorbic acid; (c) interaction of the metabolic product hypoxanthine with O2 in the presence of xanthine oxidase and (d) activation of phospholipase by calcium influx with enhanced arachidonic acid metabolism and superoxide radical production. Detailed in vitro radiobiological studies [4] have demonstrated that free radical reactions occur even at very low O2 tensions (83% of maximum rate of PO2 approximately 6 mmHg and 50% at PO2 approximately 1 mmHg), and Smith [5] has demonstrated that free radical peroxidation takes place quite rapidly in rat brain homogenates incubated in gas mixtures containing only 5% O2. Thus, the low oxygen tensions in ischemic tissue are adequate to support free radical reactions. The free radicals thus produced may initiate and enhance lipid peroxidation by attacking polyunsaturated membrane lipids.
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PMID:Production of free radicals and lipid peroxides in early experimental myocardial ischemia. 631 60

Xanthine dehydrogenase was purified from soybean nodules and the kinetic properties were studied at pH 7.5. Km values of 5.0 +/- 0.6 and 12.5 +/- 2.5 microM were obtained for xanthine and NAD+, respectively. The pattern of substrate dependence suggested a Ping-Pong mechanism. Reaction with hypoxanthine gave Km's of 52 +/- 3 and 20 +/- 2.5 microM for hypoxanthine and NAD+, respectively. The Vmax for this reaction was twice that for the xanthine-dependent reaction. The pH dependence of Vmax gave a pKa of 7.6 +/- 0.1 for either xanthine or hypoxanthine oxidation. In addition the Km for xanthine had a pKa of 7.5 consistent with the protonated form of xanthine being the true substrate. Km for hypoxanthine varied only 2.5-fold between pH 6 and 10.7. Product inhibition studies were carried out with urate and NADH. Both products gave mixed inhibition with respect to both substrates. Xanthine dehydrogenase was able to use APAD+ as an electron acceptor for xanthine oxidation, with a Km at pH 7.5 of 21.2 +/- 2.5 microM and Vmax the same as that obtained with NAD+. Reduction of APAD+ by NADH was also catalyzed by xanthine dehydrogenase with a Km of 102 +/- 15 microM; Vmax was approximately 2.5 times that for the xanthine-dependent reaction, and was independent of pH between 6 and 9. Reaction with group-specific reagents indicated the possibility of an essential histidyl group. A thiol-modifying reagent did not cause inactivation of the enzyme. A role for the histidyl side chain in catalysis is proposed.
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PMID:Soybean nodule xanthine dehydrogenase: a kinetic study. 657 70

Normal tissue toxicity of nitroaromatic radiosensitizers may originate in radiosensitizer/nitroreductase interaction. A study of two mammalian cell nitroreductases, xanthine oxidase and NADH cytochrome c reductase, shows that the efficiency of electron transfer is dependent on sensitizer electron affinity and not lipid solubility. Misonidazole and its demethylated metabolite (RO-05-9963), for example, are equally efficient as electron acceptors from xanthine oxidase. The only exception to the electron affinity correlation is m-nitrobenzamidine hydrochloride (MNBAM) which results because MNBAM inhibits electron donation to xanthine oxidase from its cofactor, xanthine. Allopurinol inhibits electron transfer and might be a useful adjuvant to the use of radiosensitizers. Evidence that allopurinol interacts with nitroreductases in vivo is deduced from the observation that allopurinol significantly alters the serum lifetimes in mice of misonidazole and RO-05-9963.
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PMID:Structure-function dependence and allopurinol inhibition of radiosensitizer/nitroreductase interaction: approaches to improving therapeutic ratios. 677 Oct 29

Various kinds of flavoenzymes such as NADPH-cytochrome c reductase, NADH-cytochrome b5 reductase, xanthine oxidase, lipoamide dehydrogenase and NADH dehydrogenase supplemented with their electron donors exhibited the sulfoxide reductase activity in the presence of a partially purified soluble factor from guinea pig liver. The present study suggests that new electron transfer systems in which the soluble factor functions as an electron carrier coupled with flavoenzymes described above are responsible for the sulfoxide reduction.
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PMID:Further studies of sulfoxide-reducing enzyme system. 679 35


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