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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The polyamines putrescine, spermidine and spermine, at concentrations of 10 microM, stimulated superoxide generation by human polymorphonuclear leukocytes induced by fMet-Leu-Phe in the presence of Ca2+. This positive effect was not evident in the absence of Ca2+ or when the polymorphonuclear leukocytes were stimulated by phorbol myristate acetate. Spermidine in the range of 10-100 microM showed a dose-dependent stimulatory effect on the superoxide generation induced by fMet-Leu-Phe, whilst at doses above 25 mM it produced an inhibitory effect. At this concentration, spermidine did not reduce the phorbol myristate acetate-neutrophil-induced O2-. generation, while an inhibitory effect by the polyamine was evident at concentrations above 50 mM. In addition, 100 microM spermidine increased the amount of superoxide generated and enhanced the ability of the chemotactic peptide to stimulate superoxide generation. The polyamines in the range of 10 microM-25 mM did not modify the activity of purified NADPH oxidase, nor the rate of reduction of cytochrome c as supported by the xanthine/xanthine oxidase reaction. These results indicate that physiological concentrations of polyamines can stimulate superoxide formation by polymorphonuclear leukocyte cells produced by the chemotactic peptide fMet-Leu-Phe, probably by increasing the availability of external calcium.
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PMID:Polyamines stimulate superoxide production in human neutrophils activated by N-fMet-Leu-Phe but not by phorbol myristate acetate. 304 Jan 18

Haemocuprein was discovered fifty years ago by T. Mann and D. Keilin as a copper protein of red blood cells, later named erythrocuprein. Superoxide dismutase was discovered twenty years ago by J.M. McCord and I. Fridovich as an enzymatic activity in preparations of carbonic anhydrase or myoglobin that inhibited the aerobic reduction of cytochrome c by xanthine oxidase. Astonishingly the superoxide dismutase proved to be haemocuprein. Around this time zinc was found in haemocuprein, in equimolar amount to the copper. Haemocuprein thus became copper-zinc superoxide dismutase after thirty years as an obscure cuproprotein of red blood cells. This historical article is a tribute to the achievement of J.M. McCord and I. Fridovich. Their discovery of superoxide dismutase revolutionized the study of oxygen free-radicals in biochemistry.
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PMID:From haemocuprein to copper-zinc superoxide dismutase: a history on the fiftieth anniversary of the discovery of haemocuprein and the twentieth anniversary of the discovery of superoxide dismutase. 306 13

We have investigated the nitroreduction of the 2-nitroimidazole benznidazole (BENZO) to its corresponding amine by murine normal tissues and tumours. In vivo concentrations of BENZO and its amine metabolite were measured by HPLC 3 hr after BENZO, 2.5 mmoles kg-1 i.p. This gave plasma and tissue BENZO concentrations of 96-160 micrograms ml-1 or g-1. Mouse plasma, KHT and RIF-1 tumour BENZO amine concentrations were very low (0.3-1.4 micrograms g-1); kidney and EMT6 tumours had intermediate levels; and liver contained very high amine levels (approximately 50 micrograms g-1). Three per cent of the BENZO dose was recovered as amine in the 24 hr urine, compared to 5% for the parent compound. Nitroreduction to the amine was demonstrated with liver and tumour preparations under N2 in vitro. The reaction was highly dependent on NADPH, and inhibited extensively in air. With liver microsomes and whole homogenates 2 and 3 moles respectively of BENZO were consumed per mole of amine formed. Inhibitor studies showed that NADPH: cytochrome P-450 (cytochrome c) reductase and cytochrome P-450 were both involved in BENZO reduction, predominantly at early and late reduction steps respectively. Aldehyde oxidase contributed to the cytosolic nitroreduction. Purified buttermilk xanthine oxidase also reduced BENZO to its amine under anaerobic conditions in vitro, but very inefficiently. The apparent Km and Vmax for BENZO amine production by whole liver homogenates were 0.148 mM and 1.45 nmole min-1 mg-1 protein respectively. Tumour homogenates were less active than liver; e.g. Vmax for the KHT tumour was 6-10-fold lower.
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PMID:Nitroimidazole bioreductive metabolism. Quantitation and characterisation of mouse tissue benznidazole nitroreductases in vivo and in vitro. 310 39

The active site arginine-143 of human Cu,Zn superoxide dismutase has been replaced by lysine or by isoleucine. The mutant proteins were expressed at high levels in yeast, purified, and the amino acid substitution explored through the use of group specific reagents. The specific activities of these enzymes, measured by the xanthine oxidase/cytochrome c method and by using dry weight determination to establish protein concentration, were: native enzyme, 6570 units/mg; Lys-substituted enzyme, 2840 units/mg, Ile-substituted enzyme, 708 units/mg. The active site arginine thus plays an important, but not an essential, role in the catalytic process.
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PMID:Examination of the role of arginine-143 in the human copper and zinc superoxide dismutase by site-specific mutagenesis. 311 54

Vanadate-dependent oxidation of NADH by xanthine oxidase does not require the presence of xanthine and therefore is not due to cooxidation. Addition of NADH or xanthine had no effect on the oxidation of the other substrate. Oxidation of NADH was high at acid pH and oxidation of xanthine was high at alkaline pH. The specific activity was relatively very high with NADH. Concentration-dependent oxidation of NADH Concentration-dependent oxidation of NADH was obtained in the presence of the polymeric form of vanadate, but not orthovanadate or metavanadate. Both NADH and NADPH were oxidized, as in the nonenzymatic system. Oxidation of NADH, but not xanthine, was inhibited by KCN, ascorbate, MnCl2, cytochrome c, mannitol, Tris, epinephrine, norepinephrine, and triiodothyronine. Oxidation of NADH was accompanied by uptake of oxygen and generation of H2O2 with a stoichiometry of 1:1:1 for NADH:O2:H2O2. A 240-nm-absorbing species was formed during the reaction which was different from H2O2 or superoxide. A mechanism of NADH oxidation is suggested wherein Vv and O2 receive one electron each successively from NADH followed by VIV giving the second electron to superoxide and reducing it to H2O2.
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PMID:Vanadate-stimulated NADH oxidation by xanthine oxidase: an intrinsic property. 363 90

New evidence in support of zinc's role as a membrane antioxidant is presented. Human erythrocyte membranes in buffered saline underwent catalase- and superoxide dismutase-inhibitable lipid peroxidation when incubated with xanthine, xanthine oxidase, and Fe(III). Free radical mediated peroxidation was measured in terms of thiobarbituric acid reactivity and iodometric determination of lipid hydroperoxides. Whereas Ca(II) had relatively little effect on lipid peroxidation, Zn(II) strongly inhibited the reaction and suppressed peroxidation-dependent lysis of resealed membranes. Inhibition of lipid peroxidation was essentially complete in the presence of 0.1 mM Zn(II), a concentration equivalent to that of added Fe(III). By contrast, Zn(II) had no effect on rose bengal-photosensitized lipid peroxidation, a predominantly nonradical, singlet oxygen-driven process. Zinc(II) also interfered with xanthine/xanthine oxidase/iron-induced peroxidation of Triton X-100-dispersed membranes, but had no effect if EDTA was present. Trivial reasons for inhibition, for example, inactivation of xanthine oxidase or complex formation with O2-, were ruled out by showing that the rate of reduction of cytochrome c by xanthine/xanthine oxidase is not affected by Zn(II). We speculate that Zn(II) acts by interfering with the redox cycling of iron, possibly by competing with the latter for membrane binding sites.
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PMID:Inhibitory effect of zinc(II) on free radical lipid peroxidation in erythrocyte membranes. 384 4

The ability of various antibiotics to inhibit superoxide anion(O-2)-mediated formation of adrenochrome from adrenaline and recovery of cytochrome c by xanthine oxidase was studied. In the adrenaline system (pH 10.2), aminoglycosides might be arranged, according to the inhibitory effect, in the following order: monomycin greater than gentamicin greater than kanamycin greater than lincomycin greater than streptomycin. In the xanthine oxidase system (pH 7.8), that order was the following: monomycin greater than gentamicin greater than lincomycin greater than greater than kanamycin. It was suggested that the antibiotic inhibition of the O-2-dependent processes at the essential sites of metabolism and/or the antibiotic involvement into the process of free radical oxidation initiated by O-2 in the cells might be one of the mechanisms of the drug action and toxicity with respect to the host.
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PMID:[Inhibition of superoxide-dependent processes by aminoglycoside antibiotics]. 609 35

Egg yolk phosphatidylcholine monolamellar liposomes (1000 A in diameter) loaded with cytochrome c were placed into an external solution, in which superoxide radicals, O2-., were generated by a xanthine-xanthine oxidase system. The penetration of the superoxide radicals across the liposomal membrane was detected by cytochrome c reduction in the inner liposome compartment. The effects of modifiers and temperature on this process were studied. The permeability of liposomal membrane for O2-. (P'O-2 = (7.6 +/- 0.3) X 10(-8) cm/s), or HO.2 (P'HO.2 = 4.9 X 10(-4) cm/s) were determined. The effect of the transmembrane electric potential (K+ concentration gradient, valinomycin) on the permeability of liposomal membranes for O2-. were investigated. It was found that O2-. can penetrate across liposomal membrane in an uncharged form. The feasibility of penetration of superoxide radicals through liposomal membrane, predominantly via anionic channels, was demonstrated by the use of an intramolecular cholesterol-amphotericin B complex.
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PMID:Permeability of bilayer lipid membranes for superoxide (O2-.) radicals. 609 12

Superoxide dismutase (SOD) activity was measured by seven assay methods. The nitrite method was found to be the best for our SOD assay kit. This method was then modified to give better sensitivity and minimize interference by coexisting protein, a factor which has been previously ignored. Hydroxylamine or its O-sulfonic acid, xanthine oxidase, hypoxanthine, EDTA, and the sample were incubated with or without KCN at pH 8.2, 37 degrees C, for 30 min. Diazo dye-forming reagent was added and the absorption was measured at 550 nm. Human plasma and erythrocyte lysate from healthy adults and Down's syndrome patients were assayed by this SOD kit and by the cytochrome c method. Our kit gave 8.5 times higher sensitivity than the cytochrome c method. This high sensitivity allowed the use of a simple spectrophotometer and, moreover, only one dilution was needed to determine the SOD unit with the help of our formulas. Good recovery, reproducibility, and stability of reagents were demonstrated.
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PMID:Reevaluation of assay methods and establishment of kit for superoxide dismutase activity. 609 57

Changes in superoxide dismutase (SOD) activity were studied in vitro at increasing NaCl or KCl concentrations. SOD activity was measured using two different systems of superoxide radical generation: pyrogallol autoxidation, and xanthine-xanthine oxidase reaction. Pyrogallol autoxidation was directly measured by spectrophotometry, whereas in the second case cytochrome c reduction was followed at 550 nm. The inhibition of SOD on those parameters was taken as measure of SOD activity. Increasing concentrations of NaCl and KCI significantly increased the rate of pyrogallol autoxidation. The inhibitory effect of SOD significantly decreased under the influence of these salts and followed an exponential curve. The two salts studied resulted in essentially identical changes in SOD activity. Increasing concentrations of NaCl and KCl decreased the rate of cytochrome c reduction in the xanthine-xanthine oxidase system. When correcting the results for these primary effects, SOD activity also displayed in this system an exponential decay with increasing salt concentrations. The results are interpreted in terms of the known charge distribution pattern on the surface of the SOD molecule, and of the age-dependent increase of the intracellular potassium and sodium concentrations in the postmitotic cells.
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PMID:Effects of ionic strength on the activity of superoxide dismutase in vitro. 609 11


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