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 luminol-dependent chemiluminescence (CL) response in vitro of guinea-pig C. parvum-activated peritoneal macrophages to platelet activating factor (PAF) has been compared with that to opsonized zymosan (OpZ). The response to PAF (5 X 10(-6) mol/l.) reached a peak within 1 min, that to OpZ (0.17 mg/ml) within 10-20 min. Peak responses to both stimuli were dose-dependently inhibited in a similar manner by p-hydroxymercuribenzoate (10(-5) - 10(-3) mol/l), sodium benzoate (10(-5) - 10(-3) mol/l.) and quinacrine (10(-6) - 10(-3) mol/l.). In contrast, the xanthine oxidase inhibitor allopurinol (IC50 vs OpZ, 220 mumol/l.; vs PAF greater than 1000 mumol/l.), the methylation-inhibiting combination homocysteine + 3-deazaadenosine (IC50 vs OpZ, 22 mumol/l.; vs PAF greater than 100 mumol/l.), the phospholipase A2 inhibitor and alkylating agent p-bromophenacylbromide (pBPB; IC50 vs OpZ, 2.6 mumol/l.; vs PAF 15 mumol/l.) and the beta-adrenoceptor agonist isoprenaline (IC50 vs OpZ, 0.1 mumol/l.; PAF greater than 10 mumol/l.) all exerted differential inhibitory effects on the CL responses to the two stimuli, though colour quenching by adrenochrome cannot be ruled out in the differential effect of isoprenaline. In screening studies, carried out with CL responses measured 2 or 5 min after PAF and OpZ, respectively, verapamil (less than or equal to 10(-4) mol/l.), trifluoperazine (less than or equal to 10(5) mol/l.) EDTA (less than or equal to 10(6) mol/l.), mannitol (less than or equal to 10(-2) mol/l.), metyrapone (less than or equal to 10(-5) mol/l.), SQ 22536 (less than or equal to 10 micrograms/ml.), iso-butyl methylxanthine (less than or equal to 10(-5) mol/l.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological analysis of guinea-pig macrophage chemiluminescence responses to platelet activating factor and opsonized zymosan. 380 36

The presence of antigenically active xanthine oxidase was indicated in various relatively purified preparations of sulfhydryl oxidase obtained from bovine milk. Evidence for formation of a complex of the two enzymes was obtained by double immunodiffusion. Furthermore, sodium dodecylsulfate-gel electrophoresis of sulfhydryl oxidase and xanthine oxidase model mixtures indicated that high molecular weight species were present that reacted with both antisulfhydryl oxidase and antixanthine oxidase. Similar gel electrophoretic patterns visualized by protein-dye binding methods revealed a distinct band (greater than 200 kdalton) was formed upon incubation of mixtures of the two enzymes, the presence of which was unaffected by reduction of protein disulfide bonds. Immunofluorescent staining techniques showed both enzymes in the apical plasma membrane. Because sulfhydryl oxidase previously has been shown to catalyze conversion of the dehydrogenase form of xanthine oxidase to the oxidase form, this conversion may occur when xanthine oxidase contacts sulfhydryl oxidase in the apical plasma membrane. This conversion and the resulting potential for production of active oxygen species could be significant to membranotropic processes, such as fat globule secretion, and to the oxidative stability of the milk fat globule membrane.
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PMID:Association of sulfhydryl oxidase and xanthine oxidase in bovine mammary tissue. 380 56

[3H]1-Nitropyrene was administered at a dose of 25 mg/kg by i.p. injection to female Wistar rats. Animals were killed 24 h later and DNA was isolated from kidney, liver and mammary gland, enzymically hydrolysed and analysed by reverse-phase h.p.l.c. A major adduct peak was detected in DNA from each of the three organs. Enzymic hydrolysates of DNA, which had been reacted in vitro with 1-nitropyrene in the presence of xanthine oxidase, were similarly analysed by h.p.l.c. One major adduct peak was obtained which had the same retention time as the in vivo product. Confirmatory evidence that the in vivo adduct and the in vitro adduct were structurally similar was obtained from the determination of the pH-dependent solvent partitioning profiles. Further, treatment of the in vivo adduct from liver, kidney or mammary gland DNA hydrolysates and the in vitro adduct with sodium hydroxide resulted in the formation of a more polar product which eluted earlier on h.p.l.c. This behaviour is consistent with scission of the imidazole ring of a deoxyguanosine adduct. The major DNA adduct formed in vitro following xanthine oxidase reduction of 1-nitropyrene has previously been identified by others as N-(deoxyguanosin-8-yl)-1-aminopyrene. The present data suggest that the in vivo 1-nitropyrene-DNA adduct has the same structure.
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PMID:Evidence for N-(deoxyguanosin-8-yl)-1-aminopyrene as a major DNA adduct in female rats treated with 1-nitropyrene. 383 6

We studied the effects of vitamin C (sodium ascorbate) on the genotoxicity of oxygen radicals to tissue culture cells. Chinese hamster ovary cells (CHO cells), when exposed to an enzymatic oxygen radical generating system (xanthine oxidase plus hypoxanthine), develop increased numbers of sister-chromatid exchanges (SCEs). Inclusion of ascorbate in these incubations resulted in significant, but variable effects. In some cases, ascorbate (less than 0.1 mM) was protective and fewer SCEs were produced. In others, significant augmentation of oxygen radical-induced SCEs occurred. These experiments illustrate the complexity of the interactions of ascorbate in biologic systems and the difficulty of predicting a desirable or harmful effect.
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PMID:The effect of vitamin C on oxygen radical-induced sister-chromatid exchanges. 383 99

Incubation of rat brain synaptosomes with xanthine and xanthine oxidase (X/XO) resulted in an inhibition of gamma-aminobutyric acid (GABA) uptake. The inhibitory effects of X/XO were temperature- and time-dependent, and were characterized by an increased Km for GABA and a decreased Vmax. Inhibition of GABA uptake by X/XO was associated with both the formation of malonyldialdehyde (MDA) and conjugated dienes, indicating that lipid peroxidation was involved. Studies with catalase, superoxide dismutase (SOD), mannitol, and chelated iron suggested that hydroxyl radical (OH X) was probably responsible for the initiation of lipid peroxidation. Both the peroxidation of synaptosomal membranes and the inhibition of GABA uptake by X/XO were enhanced by the addition of ADP and FeCl2. The X/XO-induced inhibition of GABA uptake by synaptosomes could be prevented by preincubation of synaptosomes with certain glucocorticoids prior to X/XO exposure. Methylprednisolone sodium succinate (MPSS), dexamethasone sodium phosphate (DMSP), and prednisolone sodium succinate (PSS) all prevented the inhibition of GABA uptake by X/XO. MPSS was most effective at concentrations around 100 microM, DMSP was slightly more potent, and PSS was optimal at around 300 microM. On the other hand, hydrocortisone sodium succinate (HCSS) was ineffective at preventing X/XO-induced inhibition of GABA uptake at concentrations up to 3 mM. The steroids are presumed to work through a mechanism that blocked the formation of lipid peroxides, as MPSS inhibited the formation of conjugated dienes in synaptosomes exposed to X/XO at a concentration that also protected GABA uptake.
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PMID:Lipid peroxidation-induced inhibition of gamma-aminobutyric acid uptake in rat brain synaptosomes: protection by glucocorticoids. 388 88

The milk-fat-globule membrane (MFGM) was isolated from guinea-pig milk and the membrane-associated proteins and glycoproteins characterized by electrophoretic techniques. Major components of the membrane included PAS-I, a sialoglycoprotein of Mr greater than or equal to 200000, the redox enzyme xanthine oxidase and the glycoprotein, butyrophilin. Membrane preparations also contained two other glycoproteins, GP-80 and GP-55, of Mr 80000 and 55000, respectively. Comparison of guinea-pig xanthine oxidase and butyrophilin with proteins from bovine MFGM by peptide mapping procedures, showed that the two proteins in both species were similar, but not identical. GP-55 may also be related to glycoproteins of Mr 45000 and 48000 in the bovine membrane. The integral and peripheral components of guinea-pig MFGM were identified by treating membrane preparations with sodium carbonate solutions at high pH and by partitioning the membrane proteins in solutions of Triton X-114. By these criteria xanthine oxidase and GP-55 appeared to be peripheral components and GP-80 an integral protein of the membrane. PAS-I and butyrophilin displayed hydrophilic properties in Triton X-114 solutions, but could not be removed from membrane preparations with sodium carbonate. Possible reasons for these ambiguous data are discussed. The observed similarity between several of the proteins of guinea-pig and bovine MFGM implies that these proteins may have specific functions related to milk secretion in mammary tissue, e.g. in the budding of milk-fat globules or the exocytosis of milk protein and lactose at the apical surface.
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PMID:Identification and characterization of the principal proteins of the fat-globule membrane from guinea-pig milk. 402 34

The composition of milk xanthine oxidase has been reinvestigated. When the enzyme is prepared by methods that include a selective denaturation step in the presence of sodium salicylate the product is obtained very conveniently and in high yield, and is homogeneous in the ultracentrifuge and in recycling gel filtration. It has specific activity higher than previously reported preparations of the enzyme and its composition approximates closely to 2mol of FAD, 2g-atoms of Mo and 8g-atoms of Fe/mol of protein (molecular weight about 275000). In contrast, when purely conventional preparative methods are used the product is also homogeneous by the above criteria but has a lower specific activity and is generally comparable to the crystallized enzyme described previously. Such samples also contain 2mol of FAD/mol of protein but they have lower contents of Mo (e.g. 1.2g-atom/mol). Amino acid compositions for the two types of preparation are indistinguishable. These results confirm the previous conclusion that conventional methods give mixtures of xanthine oxidase with an inactive modification of the enzyme now termed ;de-molybdo-xanthine oxidase', and show that salicylate can selectively denature the latter. The origin of de-molybdo-xanthine oxidase was investigated. FAD/Mo ratios show that it is present not only in enzyme purified by conventional methods but also in ;milk microsomes' (Bailie & Morton, 1958) and in enzyme samples prepared without proteolytic digestion. We conclude that it is secreted by cows together with the active enzyme and we discuss its occurrence in the preparations of other workers. Studies on the milks of individual cows show that nutritional rather than genetic factors determine the relative amounts of xanthine oxidase and de-molybdo-xanthine oxidase. A second inactive modification of the enzyme, now termed ;inactivated xanthine oxidase', causes variability in activity relative to E(450) or to Mo content and formation of it decreases these ratios during storage of enzyme samples including samples free from demolybdo-xanthine oxidase. We conclude that even the best purified xanthine oxidase samples described here and by other workers are contaminated by significant amounts of the inactivated form. This may complicate the interpretation of changes in the enzyme taking place during the slow phase of reduction by substrates. Attempts to remove iron from the enzyme by published methods were not successful.
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PMID:The composition of milk xanthine oxidase. 544 74

1. The reaction of milk xanthine oxidase with iodoacetamide has been studied with the silver-silver iodide electrode. 2. The reaction proceeds considerably faster in the presence of xanthine than in its absence. Anaerobically, with excess of xanthine, the reaction takes place as a rapid phase in which the enzyme is inactivated and in which approx. 1 thiol group/mol. of enzyme reacts and as a slower phase in which about 12 groups/mol. react. 3. The rapid reaction appears to be first-order with respect to xanthine oxidase and iodoacetamide and independent of the xanthine concentration with more than about 3mol. of xanthine/mol. of enzyme. 4. The velocity constant of the rapid phase is 0.26min.(-1) at 25 degrees and pH7.0, with 1mm-iodoacetamide and 17mum-xanthine oxidase. The velocity constant for the slower phase is about one-hundredth of this value. 5. The velocities of both phases increase with increasing pH in the range 5.0-9.6. 6. Xanthine may be replaced by salicylaldehyde without affecting the rate of loss of enzymic activity. With sodium dithionite as reducing agent, the reaction is slightly faster. 7. The possible function of thiol groups in the reaction mechanism of the enzyme is discussed.
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PMID:The chemistry of xanthine oxidase. Reaction with iodoacetamide. 595 74

The origin of luminol-dependent chemiluminescence (CL) in neutrophils stimulated by immune complexes (IC) was investigated. It was found that CL induced by soluble IC and aggregated human gamma globulin (AHG) was glucose-independent, while insoluble IC-induced CL was diminished in the absence of glucose. AHG-induced CL was not inhibited by superoxide dismutase, catalase or 2,5-dimethyl furan, but was suppressed in the presence of phenol, sodium benzoate, sodium formate and mannitol. The CL was also inhibited by inhibitors of arachidonic acid (AA) metabolism including 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, quinacrine, indomethacin and aspirin, and by prostaglandins E1 and E2, theophylline and dibutyryl cyclic AMP. Luminol-dependent CL was also studied in cell-free systems including AA plus soybean lipoxygenase, hydroperoxyeicosatetraenoic acid plus peroxidase and xanthine oxidase plus xanthine. Our results indicate that, in neutrophils exposed to soluble IC and AHG, CL is produced and this is closely linked to the formation of free radicals during the metabolism of AA. The radical(s) involved is likely to include the hydroxyl radical. In neutrophils stimulated by large aggregates of IC or micro-organisms, superoxide anion, H2O2 and singlet oxygen are also produced as a result of activation of NAD(P)H oxidase. These oxygen species function as oxidizing agents for AA metabolism and amplify the production of hydroxyl radical along the lipoxygenase (and possibly cyclooxygenase) pathway(s).
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PMID:Luminol-dependent chemiluminescence produced by neutrophils stimulated by immune complexes. 608 70

The molybdenum cofactor prepared by denaturing xanthine oxidase by heat treatment or other methods was partially purified by anaerobic gel filtration in the presence of sodium dithionite, with little loss of activity. A range of products with different elution volumes was obtained. This behaviour is apparently related to association of the molybdenum cofactor with various residual peptides. E.p.r. signals from molybdenum (V) in the active cofactor, present either in crude preparations or in purified fractions, may be generated in dimethyl sulphoxide solution by controlled oxidation carried out on the molybdenum cofactor alone or in the presence of added thiols. The g-values of the spectra suggest that in the oxidized cofactor molybdenum has one terminal oxygen ligand and four ligands from thiolate groups. It is proposed that two of these are from the organic part of the cofactor and two from cysteine residues in the protein or in residual peptides. A signal generated in high yield with little loss of cofactor activity in the presence of thiophenol has g parallel = 2.0258 and g = 1.9793. It is suggested that in this species two cysteine residues have been replaced by two thiophenol molecules. The possible usefulness of the thiophenol complex in further purification of the molybdenum cofactor is discussed.
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PMID:Studies by electron-paramagnetic-resonance spectroscopy of the environment of the metal in the molybdenum cofactor of molybdenum-containing enzymes. 609 19


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