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)

In vitro assembly or complementation of a hybrid assimilatory nitrate reductase was attained by mixing a preparation of nitrate-induced N. crassa mutant nit-1 specifically with acid-treated (pH 2.5) bovine milk or intestinal xanthine oxidase, rabbit liver aldehyde oxidase, or chicken liver xanthine dehydrogenase. The complementation reaction specifically required induced nit-1, the only nitrate reductase mutant of Neurospora that lacked xanthine dehydrogenase and was unable to use hypoxathine or nitrate as a sole nitrogen source. The complementing activities of the above acid-treated enzymes correspond to their xanthine or aldehyde oxidizing activity profiles on sucrose density gradients. The resulting soluble, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-nitrate reductases are the same as the Neurospora wild type enzyme in sucrose density gradient profile, molecular weight, substrate affinities, and sensitivity to inhibitors and temperature. By analogy to a similar in vitro complementation of nitrate reductase in mixtures of induced nit-1 and individual nonalleic Neurospora mutants, or uninduced wild type, the complemented nitrate apparently consists of an inducible protein subunit (possessing inducible NADPH-cytochrome c reductase) furnished by nit-1 and a subunit from the acid-treated xanthine or aldehyde oxidizing system which can substitute for the constitutive component furnished by the other mutants or uninduced wild type. The data suggest that Neurospora nitrate reductase and the xanthine oxidizing system and aldehyde oxidase of animals, all of which are molybdenum-containing enzymes catalyzing the reduction of nitrate to nitrite, share a highly similar protein subunit.
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PMID:In vitro assembly of Neurospora assimilatory nitrate reductase from protein subunits of a Neurospora mutant and the xanthine oxidizing or aldehyde oxidase systems of higher animals. 439 66

In the present study we examined the effect of reactive oxygen metabolites (generated by the xanthine-xanthine oxidase system), on adenosine-3',5'-cyclic monophosphate (cyclic AMP) and guanosine-3',5'-cyclic monophosphate (cyclic GMP) content in glomeruli and tubules that were isolated from rat renal cortex. Xanthine (0.1 mM)-xanthine oxidase (0.025 U/ml) significantly increased (P less than 0.001) the cyclic AMP content in glomeruli from 18 +/- 1 to 50 +/- 4 pmol/mg protein (n = 13). The response was dose dependent and was markedly inhibited (delta %-74 +/- 9, n = 3) by allopurinol (10(-3), a specific inhibitor of xanthine oxidase. Cyclic AMP content in the tubules, and the cyclic GMP content in glomeruli and tubules, were not altered by the xanthine-xanthine oxidase system. This lack of response was not due to lack of responsiveness of the tissues because parathyroid hormone caused a marked increase in the cyclic AMP content in tubules, and nitroprusside markedly increased the cyclic GMP content in glomeruli. The increase in cyclic AMP in glomeruli was due to generation of reactive oxygen metabolites rather than of other products (e.g. uric acid) of the xanthine-xanthine oxidase reaction--addition of uric acid to incubations had no effect; using another substrate for xanthine oxidase, acetaldehyde significantly increased (delta % 112 +/- 7, n = 4, P less than 0.001) the cyclic AMP content; and catalase that destroys hydrogen peroxide caused a marked inhibition (delta % -90 +/- 5, n = 4) of the response to xanthine-xanthine oxidase. The marked inhibition by catalase, and the lack of effect of superoxide dismutase (in a concentration that completely scavenged superoxide) suggested hydrogen peroxide as the responsible oxygen metabolite for the observed effect. Glucose-glucose oxidase (a system that directly generates hydrogen peroxide), and direct addition of hydrogen peroxide caused a dose-dependent increase in the cyclic AMP content in glomeruli, which further supports the role of hydrogen peroxide as the responsible species for the observed effect. Additional experiments that used prostaglandin synthesis inhibitors and antagonists of serotonin and histamine suggested that hydrogen peroxide increases cyclic AMP content in glomeruli by enhancing prostaglandin synthesis.
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PMID:Effect of enzymatically generated reactive oxygen metabolites on the cyclic nucleotide content in isolated rat glomeruli. 608 13

Brief treatment (3 min at 37 degrees C) of human neutrophils with triphenyltin chloride (TPTC1) resulted in a dose-dependent inhibition of superoxide (O2-.) production stimulated by concanavalin A+ cytochalasin D. It was considered from the following findings that the inhibition may be caused by some functional disorders of neutrophils: 1) O2-. generated by xanthine oxidase-acetaldehyde system was not inhibited by TPTC1. 2) There was no change in cell viability after treatment with TPTC1. When the other phenyltin compounds were examined, the relative potencies of inhibitory effect were shown to be in the order of TPTC1 greater than diphenyltin dichloride greater than phenyltin trichloride greater than tetraphenyltin on a molar basis. Lysosomal enzyme release caused by neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP) was also inhibited by TPTC1. These results suggest that TPTC1 inhibits the common pathway(s) of the two stimulus responses.
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PMID:[Effect of triphenyltin chloride on superoxide (O2-.) production in human neutrophils]. 609 90

The reduced forms of xanthine oxidase, xanthine dehydrogenase, aldehyde oxidase, and sulfite oxidase are inactivated by cyanide. Following gel filtration to remove excess of reductant and cyanide, the isolated enzymes remain inactive. Thiocyanate, a product of inactivation of the oxidized forms of the xanthine- and aldehyde-oxidizing enzymes by cyanide, is not released during inactivation of the reduced enzymes. Studies with [14C]cyanide show that, while stoichiometric binding is required for the onset of inactivation, its continued binding is not essential to maintenance of the inactivated state. Electron paramagnetic resonance and absorption spectroscopic studies on the isolated inactivated enzymes show that prosthetic groups other than molybdenum are fully oxidized but that the molybdenum centers are modified. Reactivation is accomplished by incubation with suitable oxidants. Aerobic reactivation of inactive sulfite oxidase required only 1 eq of ferricyanide/active site. However, under rigorously anaerobic conditions, 3 to 4 mol of ferricyanide/active site were reduced, indicating that the molybdenum centers in the inactive enzyme had been reduced below the levels attained by the native enzyme during catalysis.
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PMID:Mechanisms of inactivation of molybdoenzymes by cyanide. 624 90

Certain products of arachidonic acid have been demonstrated recently to possess chemotactic activity for human polymorphonuclear leukocytes (PMN). Enzymatic (lipoxygenase, cyclooxygenase) generation of these lipid chemotaxins proceeds through the formation of intermediate lipid peroxides. Since lipid peroxidation can be mediated by oxygen-derived free radicals, we have examined whether chemotactically active products of arachidonic acid could be produced by exposing this unsaturated fatty acid to a superoxide-generating system. A lipid with potent chemotactic activity for human PMN was produced by incubating arachidonic acid with xanthine oxidase and acetaldehyde. Generation of chemotactic activity was time-dependent and could be inhibited to the greatest extent by scavengers of singlet oxygen (i.e., histidine, uric acid, and 2,5-dimethylfuran). Inhibition was also observed with scavengers of superoxide anion radicals (i.e., superoxide dismutase), hydrogen peroxide (i.e., catalase), and hydroxyl radicals (i.e., mannitol). Silica gel thin-layer radiochromatography demonstrated a single peak with chemotactic activity (Rf = 0.33-0.38) distinct from unaltered arachidonic acid. The product of arachidonic acid was chemotactic at a concentration of 3.0 ng/ml and chemokinetic at concentrations of 0.75-1.5 ng/ml. Since PMN produce oxygen-derived free radicals and singlet oxygen upon stimulation of their plasma membrane, and since arachidonic acid is widely distributed in human tissues, free radical-mediated generations of chemotactic activity from arachidonic acid may play an important role in amplifying inflammatory responses.
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PMID:Generation of a chemotactic lipid from a arachidonic acid by exposure to a superoxide-generating system. 625 92

Listeria monocytogenes cells suspended in brain heart infusion broth or in carbonated saline solution emitted light (chemiluminescence) that could be detected by a liquid scintillation spectrometer. This chemiluminescence was inhibited by superoxide dismutase and catalase but not by the hydroxyl radical scavengers mannitol and benzoate; it was also dependent upon and proportional to the carbonate ion concentration in the medium. Organisms suspended in carbonated saline solution which had ceased to chemiluminesce immediately began to chemiluminesce again when acetaldehyde was added but not when glucose, sucrose, or xanthine was added. Acetaldehyde-induced chemiluminescence was inhibited by suproxide dismutase and catalase but not by allopurinol. Our data indicate that the superoxide anion, hydrogen peroxide, and the carbonate ion are involved in chemiluminescence by L. monocytogenes. Chemiluminescence is apparently initiated by the extracellular generation of superoxide anon by this organism. The mechanism for the production of the superoxide anion is not known, but xanthine oxidase does not appear to be involved.
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PMID:Chemiluminescence by Listeria monocytogenes. 625 42

In previous studies, we noted that Candida hyphae and pseudohyphae could be damaged and probably killed by neutrophils, primarily by oxygen-dependent nonphagocytic mechanisms. In extending these studies, amount of damage to hyphae again was measured by inhibition of [(14)C]cytosine uptake. Neutrophils from only one of four patients with chronic granulomatous disease damaged hyphae at all, and neutrophils from this single patient damaged hyphae far less efficiently than simultaneously tested neutrophils from normal control subjects. Neutrophils from neither of two subjects with hereditary myeloperoxidase deficiency damaged the hyphae. This confirmed the importance of oxidative mechanisms in general and myeloperoxidase-mediated systems in particular in damaging Candida hyphae. Several potentially fungicidal oxidative intermediates are produced by metabolic pathways of normal neutrophils, but their relative toxicity for Candida hyphae was previously unknown. To help determine this, cell-free in vitro systems were used to generate these potentially microbicidal products. Myeloperoxidase with hydrogen peroxide, iodide, and chloride resulted in 91.2% damage to hyphal inocula in 11 experiments. There was less damage when either chloride or iodide was omitted, and no damage when myeloperoxidase was omitted or inactivated by heating. Azide, cyanide, and catalase (but not heated catalase) inhibited the damage. Systems for generation of hydrogen peroxide could replace reagent hydrogen peroxide in the myeloperoxidase system. These included glucose oxidase, in the presence of glucose, and xanthine oxidase, in the presence of either hypoxanthine or acetaldehyde. In the presence of myeloperoxidase and a halide, the toxicity of the xanthine oxidase system was not inhibited by superoxide dismutase and, under some conditions, was marginally increased by this enzyme. This suggested that superoxide radical did not damage hyphae directly but served primarily as an intermediate in the production of hydrogen peroxide. The possible damage to hyphae by singlet oxygen was examined using photoactivation of rose bengal. This dye damaged hyphae in the presence of light and oxygen. The effect was almost completely inhibited by putative quenchers of singlet oxygen: histidine, tryptophan, and 1,4-diazobicyclo[2.2.2]octane. These agents also inhibited damage to hyphae by myeloperoxidase, halide, and either hydrogen peroxide or a peroxide source (xanthine oxidase plus acetaldehyde). Myeloperoxidase-mediated damage to hyphae was also inhibited by dimethyl sulfoxide, an antioxidant and scavenger of the hydroxyl radical. These data support the involvement of oxidative mechanisms and the myeloperoxidase-H(2)O(2)-halide system, in particular in damaging hyphae in vitro and perhaps in vivo as well.
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PMID:Damage to Candida albicans hyphae and pseudohyphae by the myeloperoxidase system and oxidative products of neutrophil metabolism in vitro. 625 27

A spectrophotometric method is described for the determination of 5'-nucleotidase. In combination with the enzymes nucleoside phosphorylase and xanthine oxidase, inosine, formed by hydrolysis of 5'-IMP by 5'-nucleotidase, is cleaved phosphorolytically to hypoxanthine, which is oxidized to uric acid. In the presence of ethanol, the hydrogen peroxide formed is reduced by catalase and equivalent amounts of acetaldehyde are produced. The aldehyde is dehydrogenated (NADP-dependent) by aldehyde dehydrogenase and the production rate of NADPH is recorded at 334 nm. The inhibition of the unspecific cleavage of 5'-IMP by phosphatases is examined critically.
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PMID:A new spectrophotometric method for the determination of 5'-nucleotidase. 625 57

Among the antimicrobial systems of polymorphonuclear leukocytes (PMNs) are those that are oxygen-dependent. Recent interest has been directed at the hydroxyl radical(OH.), a highly reactive reduction product of oxygen, as a possible mediator of microbicidal activity. The role of OH. in PMN microbicidal activity is discussed in relation to the observations that (1) an enzymic OH. generating system consisting of xanthine oxidase plus acetaldehyde is bactericidal, (2) phagocytosing PMNs convert substrates like methional and 5,5-dimethyl pyrroline-1-oxide to products suggestive of OH.-mediated reactions and (3) PMN-mediated microbicidal activity is partially inhibited by scavengers of OH.
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PMID:Role of hydroxyl radical in polymorphonuclear leukocyte-mediated bactericidal activity. 626 70

Oxygen radicals are suspected as being a cause of the cellular damage that occurs at sites of inflammation. The phagocytic cells that accumulate in areas of inflammation produce superoxide, hydrogen peroxide, hydroxyl radical, and probably singlet oxygen in the extracellular fluid. The mechanism by which these oxygen molecules kill cells is unknown. To determine which of the oxygen species is responsible for the cellular killing, we exposed human fibroblasts in culture to oxygen radicals generated by the enzymatic action of xanthine oxidase upon acetaldehyde. Using the amount of chromium-51 released from labeled fibroblasts as an index of cellular death, we found that cells were protected only by interventions that reduce hydrogen peroxide concentration. Agents that inactivate superoxide, hydroxyl radical, and singlet oxygen were ineffective in limiting oxygen radical-induced cellular death.
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PMID:Hydrogen peroxide causes the fatal injury to human fibroblasts exposed to oxygen radicals. 626 40


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