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)

The electron-spin relaxation of iron-sulphur centres in a range of simple proteins (ferredoxin, high-potential iron-sulphur protein and rubredoxin) was investigated by means of the temperature dependence and microwave power saturation of the EPR signal. The proteins containing [2Fe-2S] centres all showed temperature optima higher than those for [4Fe-4S] centres, but the difference between the slowest-relaxing [4Fe-4S] protein (Chromatium high-potential iron-sulphur protein) and the fastest-relaxing [2Fe-2S] protein (Halobacterium halobium ferredoxin) was small. A greater distinction was seen in the power saturation behaviour at low temperature (10--20 K). The behaviour of the signal intensity as a function of microwave power was analyzed in terms of the power for half saturation P 1/2 and the degree of homogeneous/inhomogeneous broadening. The effect of distorting the protein structure by salts, organic solvents and urea was to decrease the electron-spin relaxation rate as shown by a decreased value of P 1/2. The addition of Ni2+ as a paramagnetic perturbing agent caused an increase in the electron-spin relaxation rate of all the proteins, with the exception of adrenal ferredoxin, as shown by an increased P 1/2 and, in a few cases, broadening of the linewidth. Ferricyanide, a commonly used oxidizing agent, has similar effects. These results are discussed in relation to the use of paramagnetic probes to determine whether iron-sulphur centres are near to a membrane surface. Spin-spin interactions between two paramagnetic centres in a protein molecule such as a 2[4Fe-4S] ferredoxin, lead to more rapid electron-spin relaxation. This method was used to detect a spin-spin interaction between molybdenum V and centre Fe-SI in xanthine oxidase.
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PMID:Electron spin relaxation of iron-sulphur proteins studied by microwave power saturation. 21 17

At physiologic pH values, histidine-containing nickel(II) oligopeptides reduced the flux of superoxide anion (O2-) generated in the hypoxanthine/xanthine oxidase system. The postulated involvement of the Ni(III)/Ni(II) redox couple in this apparent dismutation receives indirect support from electron-spin resonance data. These complexes also catalyzed the disproportionation of hydrogen peroxide, a process which generates active intermediates capable of hydroxylating p-nitrophenol and oxidizing uric acid to allantoin. An oxene moiety, namely [Nio]2+, is postulated as the active species in these H2O2-dependent reactions. Spectral analysis showed that monovalent, divalent and trivalent ions induced cooperative conformational changes in synthetic polydeoxynucleotides. For the nickel(II) ion, resistance to DNase-I activity clearly showed that an alternating G-C sequence is required for the observed transitions. It is concluded that the ability of nickel(II) peptide complexes to participate in active oxygen biochemistry suggests a possible role for nickel as a chemical promoter of cancer, whereas the capacity of the nickel(II) ion to induce conformational changes in DNA could, in principle, affect gene expression. Of course, the validity of both hypotheses require that the observed reactions be verified as biologically significant.
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PMID:Superoxide dismutase activity and novel reactions with hydrogen peroxide of histidine-containing nickel(II)-oligopeptide complexes and nickel(II)-induced structural changes in synthetic DNA. 248 92

Adriamycin and mitomycin C were reduced by xanthine oxidase/NADH in the presence of a DNA template comprising a stable initiated ternary transcription complex derived from the lac UV5 promoter. Subsequent elongation of the transcription complex treated with mitomycin C revealed high levels of terminated transcripts one nucleotide prior to G residues on the coding strand (i.e. at X of XpC sequences of the non-coding strand). Lower levels of termination occurred with adriamycin, and these were also one nucleotide prior to G residues of the coding strand, but with greater sequence specificity since they were observed mainly at G of GpC sequences of the non-coding strand. The same sites were also observed with adriamycin in the absence of reducing conditions and the level of termination at these sites was enhanced up to 10-fold by Fe2+ and Fe3+, but not by Cu2+, Zn2+, Co2+ or Ni2+. These results suggest that an iron-adriamycin complex with DNA is highly sequence-specific and results in adducts, similar to those of mitomycin C, which can terminate the transcription process. Such a mechanism offers new insights into the possible mode of action of anthracyclines.
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PMID:DNA sequence-specific adducts of adriamycin and mitomycin C. 249 87

Copper(II) and nickel(II) complexes of macrocyclic polyamine derivatives possessing partial oligopeptide-like structures are found to suppress the xanthine-xanthine oxidase-mediated reduction of nitroblue tetrazolium and also to suppress formazan formation by potassium superoxide. The activity in the superoxide dismutase assay is dependent on ring size, type and number of donor atoms, metal ion, and substituents on the macrocycles. Some of those are more active than the known O2- scavengers such as copper(II)-salicylate and copper(II)-amino acid (or peptide) complexes. Nickel (II)-naphthylmethyl-dioxo-[16]ane N5, 13, 1:1 complex (NiH-2L) is the most active among the 30 chelates examined.
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PMID:Superoxide dismutase activity of macrocyclic polyamine complexes. 689 4

The inhibition of the activity of bovine xanthine oxidase (XO) by divalent mercury and other metal ions has been investigated by optical spectroscopy and stop-flow kinetic measurements. The study shows that Hg2+ ion completely inhibits the activity of XO, while other metal ions such as Zn2+, Mg2+, Co2+, and Ni2+ inhibit the activity only marginally (approximately 10%). The inhibition by the Hg2+ ion was found to be monophasic and noncompetitive with strong affinity for binding to XO. The pH-dependent study of the inhibition indicates that at least two ionizing groups of XO are involved in the binding of the Hg2+ ion.
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PMID:The inhibition of bovine xanthine oxidase activity by Hg2+ and other metal ions. 867 4

Oxygen-derived free radicals (OFR) have been implicated in the pathogenesis of intracellular Ca2+ overload and the arrhythmias that characterize cardiac reperfusion. These arrhythmias may in large part be due to activation of the pathological transient inward current (ITI). However, the identity of the ITI generated by OFR is uncertain. We previously found that H2O2, an OFR-generating compound, markedly stimulated the ITI elicited by brief caffeine pulses in patch-clamped guinea pig ventricular myocytes. In the present study, using patch-clamped rabbit ventricular myocytes loaded with the Ca(2+)-sensitive indicator fura 2, we have further characterized this ITI and have identified its major component to be Na+/Ca2+ exchange based on its dependence on extracellular Na+ and sarcoplasmic reticulum Ca2+ release, its sensitivity to Ni2+, and the effects of its inhibition on relaxation. The effect on ITI was not unique to H2O2, because another free radical-generating system, xanthine + xanthine oxidase, produced a similar response. We hypothesize that enhancement of Na+/Ca2+ exchange by OFR during reperfusion, when intracellular Na+ is elevated, may promote intracellular Ca2+ overload and triggered arrhythmias.
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PMID:Free radicals enhance Na+/Ca2+ exchange in ventricular myocytes. 885 14

1. The mode of action of reactive oxygen intermediates in cysosolic Ca2+ movements of cultured porcine aortic endothelial cells exposed to xanthine/xanthine oxidase (X/XO) was investigated. 2. Cytosolic Ca2+ movements provoked by X/XO consisted of an initial Ca2+ release from thapsigargin-sensitive intracellular Ca2+ stores and a sustained Ca2+ influx through cell-membrane Ca2+ channels. The Ca2+ movements from both sources were inhibited by catalase, cell-membrane permeable iron chelators (o-phenanthroline and deferoxamine), a *OH scavenger (5,5-dimethyl-1-pyrroline-N-oxide), or an anion channel blocker (disodium 4, 4'-diisothiocyano-2, 2'-stilbenedisulphonic acid), suggesting that *O2- influx through anion channels was responsible for the Ca2+ movements, in which *OH generation catalyzed by intracellular transition metals (i.e., Haber-Weiss cycle) was involved. 3. After an initial Ca2+ elevation provoked by X/XO, cytosolic Ca2+ concentration decreased to a level higher than basal levels. Removal of X/XO slightly enhanced the Ca2+ decrease. Extracellular addition of sulphydryl (SH)-reducing agents, dithiothreitol or glutathione, after the removal of X/XO accelerated the decrement. A Ca2+ channel blocker, Ni2+, abolished the sustained increase in Ca2+, suggesting that Ca2+ influx through cell-membrane Ca2+ channels was extracellularly regulated by the redox state of SH-groups. 4. The X/XO-provoked change in cellular respiration was inhibited by Ni2+ or dithiothreitol as well as inhibitors of Haber-Weiss cycle, suggesting that Ca2+ influx was responsible for *OH-mediated cytotoxicity. We concluded that intracellular *OH generation was involved in the Ca2+ movements in endothelial cells exposed to X/XO. Cytosolic Ca2+ elevation was partly responsible for the oxidants-mediated cytotoxicity.
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PMID:Cytosolic Ca2+ movements of endothelial cells exposed to reactive oxygen intermediates: role of hydroxyl radical-mediated redox alteration of cell-membrane Ca2+ channels. 1021 41

This study was designed to test the idea that the redox state of sulfhydryl (SH)-groups in cell-membrane Ca2+ channels plays a pivotal role in Ca2+ influx, which in turn causes an increase in albumin permeability across the cultured monolayer of porcine pulmonary artery endothelial (PPAE) cells exposed to xanthine/xanthine oxidase (X/XO). Albumin permeability as well as the concentration of intracellular Ca2+ ([Ca2+]i) was increased by X/XO. A H2O2 scavenger (catalase), an iron chelator (o-phenanthroline), and a hydroxyl radical scavenger (dimethyl sulfoxide) inhibited these changes provoked by X/XO, in which intracellular iron-catalyzed hydroxyl radical generation was suggested to be involved. The increase in albumin permeability and [Ca2+]i continued once the PPAE cells were exposed to X/XO. The [Ca2+]i was decreased by a Ca2+ channel blocker, Ni2+, while the removal of Ni2+ increased [Ca2+]i again, suggesting the sustained Ca2+ influx through cell-membrane Ca2+ channels was responsible for the [Ca2+]i elevation. Ni2+ failed to inhibit albumin permeability sustained after the removal of X/XO. In contrast, SH-reducing agents (dithiothreitol and glutathione) inhibited the sustained permeability as well as Ca2+ influx. We concluded that the redox alteration of SH-groups in cell-membrane Ca2+ channels was involved in the increase in albumin permeability after exposure of the endothelial cells to oxidative stress.
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PMID:Albumin permeability across endothelial cell monolayer exposed to reactive oxygen intermediates: involvement of reversible functional alteration of the cell membrane Ca2+ channels. 1082 58

Nickel superoxide dismutase (NiSOD) is a mononuclear nickel-containing metalloenzyme that catalyzes the disproportionation of superoxide by cycling between NiII and NiIII oxidation states. In the reduced NiII oxidation state, the metal center is ligated by two cysteinate sulfurs, one amide nitrogen, and one amine nitrogen (from the N-terminus), while in the oxidized NiIII state, an imidazole nitrogen coordinates to the metal center. Herein, we expand on a previous report in which we described a functional metallopeptide-based NiSOD model compound [NiII(SODM1)] (SODM1 = H2N-HCDLPCGVYDPA-COOH) by exploring how acylation of the N-terminus (producing [NiII(SODM1-Ac)]) influences the properties of the metallopeptide. Titration results, GPC data, and mass-spectrometry data demonstrate that NiII coordinates to SODM1-Ac in a 1:1 ratio, while variable pH studies show that NiII coordination is strong at a pH of 7.5 and above but not observed below a pH of 6.2. This is higher than [NiII(SODM1)] by approximately 1.0 pH unit consistent with bisamide ligation. Ni K-edge XAS demonstrates that the NiII center is coordinated in a square-planar NiN2S2 coordination environment with Ni-N distances of 1.846(4) A and Ni-S distances of 2.174(3) A. Comparison of the electronic absorption and CD spectrum of [NiII(SODM1)] versus [NiII(SODM1-Ac)] in conjunction with time-dependent DFT calculations suggests a decrease in Ni covalency in the acylated versus unacylated metallopeptide. This decrease in covalency was also supported by DFT calculations and Ni L-edge XAS. [NiII(SODM1-Ac)] has a quasireversible NiII/NiIII redox couple of 0.49(1) V vs Ag/AgCl, which represents a -0.2 V shift compared with [NiII(SODM1)], while the peak separation suggests a change in the coordination environment upon oxidation (i.e., axial imidazole ligation). Using the xanthine/xanthine oxidase assay, we determine that [NiII(SODM1-Ac)] is less active than [NiII(SODM1)] by over 2 orders of magnitude (IC50 = 3(1) x 10-5 vs 2(1) x 10-7 M). Possible reasons for the decrease in activity are discussed.
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PMID:The influence of amine/amide versus bisamide coordination in nickel superoxide dismutase. 1717 10

Human aldehyde oxidase 1 (AOX1) has been subcloned into a vector suitable for expression in Escherichia coli, and the protein has been expressed. The resulting protein is active, with sulfur being incorporated in the molybdopterin cofactor. Expression levels are modest, but 1 liter of cells supplies enough protein for both biochemical and kinetic characterization. Partial purification is achieved by nickel affinity chromatography through the addition of six histidines to the amino-terminal end of the protein. Kinetic analysis, including kinetic isotope effects and comparison with xanthine oxidase, reveal similar mechanisms, with some subtle differences. This expression system will allow for the interrogation of human aldehyde oxidase structure/function relationships by site-directed mutagenesis and provide protein for characterizing the role of AOX1 in drug metabolism.
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PMID:Purification and mechanism of human aldehyde oxidase expressed in Escherichia coli. 1974 Oct 35


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