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

The relationship between the structure and function of ferricytochrome c bound to the phosphoprotein phosvitin was investigated. The rates of reduction of phosvitin-bound ferricytochrome c by cytochrome b2, ascorbate and the superoxide radical generated by xanthine oxidase wer repressed where the binding ratio was less than half the maximum, but at higher ratios they were restored gradually with increase in the ratio. The affinity of cytochrome b2 for cytochrome c was not affected by binding of cytochrome c to phosvitin. The redox potential of the bond form was lower than that of the free form and only decreased with decrease in the ratio. The conformatin around the heme moiety and the electronic structure of the heme group of bound ferricytochrome c were similar to those of free ferricytochrome c, but the conformational stability in the vicinity of the prosthetic group was related to the binding ratio as ratios above half the maximum and was well correlated with the reduction rate. Since the binding of cytochrome c to phosvitin is much stronger at binding ratios below half the maximum, these results suggest that this binding strength exclusively affects the conformational flexibility of the heme crevice in the cytochrome molecule, thus altering the reduction rate.
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PMID:Relation of the structure and function of ferricytochrome c bound to the phosphoprotein phosvitin. 625 2

Hydroxyl radical production, detected by ethylene formation from methional, has been investigated in plasma, lymph and synovial fluid. In the presence of added iron--EDTA, addition of either H2O2 or xanthine and xanthine oxidase gave rise to hydroxyl radical formation that in most cases was not superoxide-dependent. The ascorbate already present in the fluid appeared to participate in the reaction. In the absence of added catalyst, the reaction was hardly detectable, the rate being less than 5% of that observed with 1 microM-iron--EDTA added. This implies that the fluids had little if any capacity to catalyse hydroxyl radical production via this mechanism.
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PMID:Hydroxyl radical production in body fluids. Roles of metal ions, ascorbate and superoxide. 627 37

The possible role of superoxide anion in 2-oxoglutarate-coupled dioxygenase reactions has been investigated. gamma-Butyrobetaine hydroxylase (EC 1.14.11.1) was inhibited by human erythrocyte superoxide dismutase (EC 1.15.1.1), probably due to release of Cu(2+) or Zn(2+), as the inhibition was more pronounced after heat-inactivation of the dismutase and as Cu(2+) was a potent inhibitor. Bovine superoxide dismutase and the Mn(2+)-containing superoxide dismutase from Escherichia coli were not inhibitory. Superoxide anion generated from xanthine/xanthine oxidase was not stimulatory and could not replace ascorbate. Thymine 7-hydroxylase (EC 1.14.11.6) and thymidine 2'-hydroxylase (EC 1.14.11.3) were not inhibited by erythrocyte superoxide dismutase or stimulated by superoxide anion. gamma-Butyrobetaine hydroxylase was inhibited by a number of low-molecular-weight compounds, such as tetranitromethane, Nitro Blue Tetrazolium, adrenaline and Tiron, which may act as scavengers of superoxide anion. Involvement of this radical in other oxygenase reactions has been inferred from the findings that they were inhibitory for the respective enzymes. Several of these compounds also inhibited gamma-butyrobetaine hydroxylase. It could be concluded from these experiments, however, that mechanisms other than disposal of superoxide anion might equally well be operative, such as hydrophobic interaction with the enzyme protein and interaction with compounds required for full enzymic activity, e.g. iron and ascorbate. The results appear to rule out a requirement for superoxide anion generated in free solution, and have not yielded evidence for participation of enzyme-bound superoxide anion in 2-oxoglutarate-dependent hydroxylations.
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PMID:Does superoxide anion participate in 2-oxoglutarate-dependent hydroxylation? 629 7

Copper (Cu2+) ions at physiological concentrations can promote the formation of hydroxyl radical (OH) or a species of equivalent reactivity. The reaction requires H2O2 and a reducing agent. Reduction of Cu2+ can be achieved by superoxide ion generated by a mixture of hypoxanthine and xanthine oxidase or added directly as its potassium salt. Reduction of Cu2+ can also be achieved by ascorbic acid. Hence both O2- -dependent and ascorbate-dependent formation of OH from H2O2 in the presence of Cu2+ can be observed. Only the former reaction is significantly inhibited by superoxide dismutase. The binding of Cu2+ to histidine or albumin at physiological concentrations decreases the formation of OH radicals in free solution in the presence of either ascorbate or an (O2- -generating system. It is suggested that OH is still formed but reacts immediately with the binding molecule.
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PMID:Superoxide-dependent and ascorbate-dependent formation of hydroxyl radicals in the presence of copper salts: a physiologically significant reaction? 631 Nov 5

The polycyclic nitroaromatic hydrocarbon 1-nitropyrene is an environmental pollutant, a potent bacterial mutagen, and a carcinogen. Xanthine oxidase, a mammalian nitroreductase, catalyzed the in vitro metabolic activation of this compound to DNA-bound adducts. Maximum adduct formation occurred at pH 5.5 to 6.0 and was increased by the addition of catalase to the incubation medium. DNA binding from 1-nitropyrene was inhibited by hydrogen peroxide, L-ascorbate, and glutathione. Enzymatic hydrolysis of the modified DNA and subsequent analysis by high-pressure liquid chromatography indicated the presence of one major and two minor adducts. The major adduct was characterized by mass spectrometry and nuclear magnetic resonance spectroscopy as N-(deoxyguanosin-8-yl)-1-aminopyrene. The minor adducts appear to be decomposition products of the major adduct. When Salmonella typhimurium TA1538 was incubated with 1-nitropyrene, a strong correlation was found between the extent of DNA binding and the frequency of induced histidine reversions. Analysis of the bacterial DNA indicated one major adduct which had chromatographic properties and pKaS identical to those of N-(deoxyguanosin-8-yl)-1-aminopyrene. These data indicate that N-hydroxy-1-aminopyrene is probably the mutagenic and DNA-binding species formed during the metabolic reduction of 1-nitropyrene.
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PMID:Formation of DNA adducts in vitro and in Salmonella typhimurium upon metabolic reduction of the environmental mutagen 1-nitropyrene. 633 47

The induction of lipid peroxidation in the eye pigment epithelium of pigmented rabbits by the Fe2+ + ascorbate and xanthine--xanthine oxidase systems did not result in accumulation of malonic dialdehyde. In albino rabbits the lipid peroxidation of the non-pigmented pigment epithelium and retina occurred at a high rate under the same conditions. The rate of lipid peroxidation also showed an increase after removal of melanoprotein granules from the pigmented pigment epithelium. The latter inhibited the rate of lipid peroxidation in the eye retina. In albino animals the rate of lipid peroxidation in a mixture of the tow tissues (i.e. pigment epithelium and retina) is almost 4 times that in the pigmented animals. Consequently, the pigmented pigment epithelium of the eye is much more resistant to the effect of prooxidant systems as compared to the non-pigmented one. It is assumed that one of the main functions of the melanoprotein granules in the eye pigment epithelium cells is their protective effect.
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PMID:[Comparative study of lipid peroxidation in the eye pigment epithelium of pigmented and albino animals]. 696 13

Degradation of deoxyribonucleic acid (DNA) by 1,10-phenanthroline has been shown to require Cu(II), a reducing agent, and O2. Other metal ions do not substitute for Cu(II), and degradation of DNA is inhibited by metal ions that can form stable complexes with 1,10-phenanthroline, such as Co(II), Cd(II), Ni(II), or Zn(II), as well as by chelators that can bind copper, such as triethyltetraamine, neocuproine, or ethylenediaminetetraacetic acid (EDTA). Neocuproine, a specific copper chelator, is more effective than EDTA in inhibiting the breakdown of DNA. The degradation of DNA shows a requirement for a reducing agent which can be satisfied by either ascorbate or a thiol. A free radical generating system, e.g., xanthine oxidase-hypoxanthine, can substitute for the reducing agent. DNA degradation, in the presence of either an organic reducing agent or xanthine oxidase-hypoxanthine, is inhibited by hydroxyl radical scavengers and by catalase, suggesting that hydroxyl radical is the reactive species in DNA degradation and that hydrogen peroxide is an intermediate in hydroxyl radical generation.
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PMID:Degradation of deoxyribonucleic acid by a 1,10-phenanthroline-copper complex: the role of hydroxyl radicals. 747 Apr 43

Intracellular reduced ascorbate (AA) levels in confluent cultures of human umbilical vein endothelial (HUVE) cells, grown under conventional conditions, were shown to be very low, ranging between undetectable, < 0.1 nmol/mg protein, and 0.3 nmol/mg protein. Reduced ascorbate was accumulated into the endothelial cells from M199 culture medium in time- and concentration-dependent manners, and was saturated at medium concentrations related to the normal plasma concentrations of the antioxidant (i.e. between 50 microM and 100 microM). Cells derived from different individuals demonstrated considerable inter-individual variation in these AA uptake parameters. The uptake of AA was sensitive to temperature and the presence of the structural analogue isoascorbate in the medium, indicating the involvement of an active transport mechanism. A role for the glucose transporter is, however, not indicated, as AA uptake was not sensitive to phloretin, an inhibitor of the cellular glucose transporter, nor greatly enhanced by depletion of glucose from the medium. Incubation of HUVE cells with dehydroascorbate (DHAA) caused a dose-dependent, but transient increase in intracellular AA. This indicates that HUVE cells are both competent in the uptake and intracellular reduction of oxidised ascorbate, and may resecrete AA into the medium. Indeed, reduced ascorbate in the medium was shown to be preferentially maintained in the presence of cells. The uptake of AA was not sensitive to the presence of DHAA in the medium, perhaps indicating different transporters for reduced and oxidised forms of ascorbate in these human cells. Pre-loading HUVE cells with AA was shown to protect control cells only weakly from the acute, sub-lethal toxicity of H2O2 generated by xanthine oxidase (1 U/mL or 10 U/mL). Protection was optimal at intracellular levels of 3-4 nmol AA/mg protein, with higher concentrations lacking a protective effect. Additionally, the presence of the iron chelator, desferoxamine, significantly protected GSH-depleted HUVE cells only in response to the peroxide, but did not potentiate the protective action of intracellular AA in either control or GSH-depleted cells. This indicates that ascorbate-driven redox-cycling of the Fe2+/Fe3+ does not hamper the intracellular protective function of ascorbate during hydrogen peroxide-derived oxidative stress. These results are discussed in terms of the central role of endothelial cells in the distribution of AA to the tissues of the body, the use of the HUVE cell system for model studies of the toxicity of oxidants in the human endothelium, and the balance between the antioxidant and pro-oxidant actions of AA.
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PMID:The uptake of ascorbic acid into human umbilical vein endothelial cells and its effect on oxidant insult. 750 81

The direct neurotoxic action of the beta-amyloid protein, the major constituent of senile plaques, may represent the underlying cause of neuronal degeneration observed in Alzheimer's disease. The apoptotic-mediated neuronal death induced by beta-amyloid appears to reside in its ability to form Ca(2+)-permeable pores in neuronal membranes resulting in an excessive influx of Ca2+ and the induction of neurotoxic cascades. It is possible that during beta-amyloid exposure a Ca(2+)-mediated increase in free radical generation may exceed the defensive capacity of cells and thus lead to cell death. Consequently, in the present study we have investigated the effect of a panoply of antioxidants and inhibitors of free radical formation on the development of beta-amyloid neurotoxicity. Acute exposure of rat hippocampal neurons to "aged" beta-amyloid25-35 peptide (5-50 microM) induced a slow, concentration-dependent apoptotic neurotoxicity (25-85%) during a 6 day exposure. Co-incubation of cultures with beta-amyloid25-35 peptide (25 microM) and inhibitors of nitric oxide synthase and/or xanthine oxidase (NG-monomethyl-L-arginine [1 mM), N omega-nitro-L-arginine [1 mM], oxypurinol [100 microM], allopurinol [100 microM]), important mediators of nitric oxide, superoxide, and hydroxyl radical formation, did not attenuate beta-amyloid neurotoxicity. Similarly, a reduction in free radical generation by selective inhibition of phospholipase-A2 cyclooxygenase, and lipoxygenase activities with quinacrine (0.5 microM), indomethacin (50 microM), and nor-dihydroguaiaretic acid (0.5 microM), respectively, did not reduce the proclivity of beta-amyloid to induce cell death. Exposure of cultures to catalase (25 U/ml) and/or superoxide dismutase (10 U/ml) as well as the free radical scavengers vitamin E (100 microM), vitamin C (100 microM), glutathione (100 microM), L-cysteine (100 microM), N-acetyl-cysteine (100 microM), deferoxamine (5 microM), or haemoglobin (35 micrograms/ml) failed to attenuate the neurotoxic action of beta-amyloid. On the other hand, pre-treatment of cultures with subtoxic concentrations of beta-amyloid peptide significantly increased the vulnerability of neurons to H2O2 exposure and suggest that beta-amyloid peptide renders neurons more sensitive to free radical attack. However, a potential beta-amyloid-mediated increase in free radical formation is not a proximate cause of the neurotoxic mechanism of beta-amyloid in vitro.
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PMID:Inhibitors of free radical formation fail to attenuate direct beta-amyloid25-35 peptide-mediated neurotoxicity in rat hippocampal cultures. 753 47

The ability of O2 metabolites derived from the xanthine-xanthine oxidase system to inhibit mitochondrial function was examined using freshly isolated rat liver mitochondria. Under 2,4-dinitrophenol-uncoupled conditions, mitochondria exposed to free radicals exhibited a significant decrease in O2 consumption supported by NAD(+)-linked substrates, but showed almost no change in O2 consumption in the presence of succinate and ascorbate. Oxidative stress caused the loss of intramitochondrial nicotinamide nucleotides, and addition of NAD+ fully prevented any fall in O2 consumption with NAD(+)-linked substrates. The activity of electron-transfer complex I (NADH oxidase and NADH-cytochrome c oxidoreductase) and the energy-dependent reduction of NAD+ by succinate were unaltered by oxidative stress. Exposure to free radicals also had an uncoupling effect at all three coupling sites. The degree of mitochondrial swelling was closely correlated with the inhibition of State-3 oxidation of site-I substrates and with the increase in State-4 oxidation of succinate. The immunosuppressive agent cyclosporin A completely prevented the mitochondrial damage induced by oxygen free radicals (swelling, Ca2+ release, sucrose trapping, uncoupling and selective inhibition of the mitochondrial respiration of site-I substrates). The same protective effect was found when Ca2+ cycling was prevented, either by chelating Ca2+ with EGTA or by inhibiting Ca2+ reuptake with Ruthenium Red. These findings suggest that the deleterious effect of free radicals on mitochondria in the present experimental system was triggered by the cyclosporin A-sensitive and Ca(2+)-dependent membrane transition, and not by direct impairment of the mitochondrial inner-membrane enzymes.
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PMID:Oxidative damage to mitochondria is mediated by the Ca(2+)-dependent inner-membrane permeability transition. 769 Oct 56


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