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)

14,15-3H-Norethisterone-4 beta, 5 beta-epoxide, a metabolite of norethisterone, was incubated with several proteins and nucleic acids. After 30 min incubation 0.19 nmol of the epoxide were irreversibly bound per mg albumin which contains free sulfhydryl groups; proteins without SH-groups, such as concanavalin A, gamma-globulin, DNA and RNA, did not irreversibly bind norethisterone epoxide. A superoxide (O2) generating enzyme system comprised of xanthine oxidase and hypoxanthine was capable of catalyzing the irreversible binding of the parent compound, norethisterone, to albumin, indicating that an oxidation product was formed which reacted with the protein. When norethisterone epoxide was incubated for 60 min with hepatic microsomes of rats in absence of NADPH, about 2.0 nmol of the epoxide were irreversibly incorporated per mg microsomal protein. This binding was increased to 5.2 nmol by addition of a NADPH regenerating system. Addition of glutathione and cytosol decreased only the NADPH-dependent protein binding; phenobarbital pretreatment of rats induced this NADPH-dependent binding of norethisterone epoxide to microsomal protein by a factor of 2. In presence of NADPH, binding of the epoxide to microsomal protein depended on substrate concentration used. The results indicate that norethisterone epoxide is able to chemically react with proteins. In addition, hepatic microsomal enzymes convert the epoxide to another metabolite which also can react with proteins.
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PMID:Irreversible protein binding of norethisterone (norethindrone) epoxide. 0 5

Lysosomes were isolated from adult male Wistar rat brain and incubated in vitro with 10 micron trichloroethylene and microsomes or postmicrosomal supernatant with added NADPH. Freezing and incubation with the solvent alone served as controls. The results were compared with the effect of peroxide anion from the xanthine-xanthine oxidase reaction. Mere solvent did not cause an appearance of acid proteinase activity in the incubation medium whereas other treatments induced lysosomal labilization.
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PMID:Labilization of brain lysosomes by trichloroethylene metabolites and peroxide anion in vitro. 2 9

A protein fraction, which did not contain NADP [or NADPH]-dependent aldehyde reductase as well as NAD [or NADP]-dependent aldehyde dehydrogenases, but which catalyzed oxidation of fatty-aromatic aldehydes, was isolated from extract of rat liver tissue using ammonium sulfate fractionation combined with gradient syvorptive chromatography on DEAE-Sephadex A-25 [or Molselect DEAE-25], CM-Sephadex C-25 and gel-filtration on Sephadex G-200. Investigations of molecular weight and catalytic properties of the protein fraction obtained enabled to identify it with xanthine oxidase [EC 1.2.3.2]. Aldehyde dehydrogenases as well as xanthine oxidase are involved in oxidation of fatty-aromatic aldehydes to corresponding fatty acids, besides the reduction of the aldehydes to alcohols, catalyzed by aldehyde reductase and alcohol dehydrogenases.
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PMID:[Oxidation of fatty-aromatic aldehydes in liver tissues]. 3 12

1. Ethanol metabolism in slices or homogenates of transplantable hepatocellular carcinoma HC-252 (HC-252) was 50 to 60% of the rate found in host liver slices or homogenates when they were expressed per gram of tissue wet weight and 70 to 80% of the liver when the rates were expressed per milligram of tissue protein. At 10 mM ethanol, the activities of alcohol dehydrogenase in tumor and liver supernatants were comparable. 2. Tumor microsomes did not oxidize ethanol in the presence of a NADPH-generating system, indicating the absence of the microsomal ethanol-oxidizing system and catalase-mediated peroxidation of ethanol. The HC-252 microsomes were contaminated with catalase, and acetaldehyde production occurred in the presence of a H2O2-generating system (xanthine oxidase). The virtual absence of ethanol oxidation and drug metabolism (aminopyrine demethylase and aniline hydroxylase) in HC-252 microsomes may be due to the low activities of NADPH-cytochrome c reductase, NADPH oxidase, and NADPH-dependent oxygen uptake. 3. Microsomal oxidation of ethanol was present in Morris hepatoma 5123C, a well-differentiated tumor of intermediate growth rate, while activity was negligible in microsomes from Morris hepatoma 7288CTC, a less differentiated tumor. Microsomal NADPH oxidase was present in the well differentiated tumor 5123C but was lacking in the less differentiated tumor 7288CTC. Several microsomal, mitochondrial, and cytosolic properties of HC-252 are similar to those of Morris hepatoma 7288CTC but differ from those of the more differentiated 5123C tumor and normal liver. 4. The content of mitochondrial protein in HC-252 was only 25% that of liver, and oxygen consumption per gram of tumor was only 28% that of the liver. When corrected for the mitochondrial protein content, oxygen uptake in tumor HC-252 and liver homogenates was comparable. Isolated tumor and liver mitochondria displayed comparable State 4 and 3 rates of oxygen consumption with succinate and glutamate as substrates. The activities of the reconstituted malate-aspartate and alpha-glycerophosphate shuttles were only slightly lower in isolated HC-252 mitochondria compared to liver mitochondria, when shuttles were reconstituted with purified enzymes. 5. Antimycin inhibited alcohol metabolism,and pyruvate stimulated alcohol metabolism, much less in tumor slices than in liver slices, suggesting the presence of an augmented mitochondria-independent, cytosolic mechanism for oxidizing reducing equivalents in the tumor. These factors suggest that oxidation of NADH is the limiting factor in ethanol metabolism. Whereas, in the liver mitochondrial reoxidation is predominant, in HC-252, cytosolic reoxidation of NADH also plays a major role.
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PMID:Ethanol metabolism by a transplantable hepatocellular carcinoma. Role of microsomes and mitochondria. 13 37

A molybdenum cofactor (Mo-co) from xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2) can be isolated from the enzyme by a technique that has been used to isolate an iron-molybdenum cofactor (FeMo-co) from component I of nitrogenase. N-Methylformamide is used for the extraction of these molybdenum cofactors. Mo-co from xanthine oxidase activates nitrate reductase (NADPH:nitrate oxidoreductase, EC 1.6.6.2) in an extract from Neurospora crassa mutant strain Nit-1; however, FeMo-co is unable to activate nitrate reductase in strain Nit-1. Mo-co from xanthine oxidase is unable to activate nitrogenase in an extract of Azotobacter vinelandii mutant strain UW45. Inactive component I in this extract can be activated by FeMo-co. These results indicate that nitrate reductase and xanthine oxidase share a common molybdenum cofactor, but this cofactor is different from the molybdenum cofactor in nitrogenase.A. vinelandii synthesizes both Mo-co and FeMo-co. Mo-co is produced when the cells fix N(2) and also when they are repressed for nitrogenase synthesis by growth in a medium containing excess ammonium. However, FeMo-co is not produced when cells are grown in an ammonium-containing medium. Partially purified preparations of component I from A. vinelandii and Klebsiella pneumoniae contain both FeMo-co and Mo-co. The presence of both FeMo-co and Mo-co activities in partially purified preparations of component I explains previous reports of activation of inactive nitrate reductase in strain Nit-1 by acid-treated component I of nitrogenase. The Mo-co can be separated from FeMo-co in these preparations by chromatography on Sephadex G-100 in N-methylformamide. Both FeMo-co and Mo-co are sensitive to oxygen.
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PMID:Molybdenum cofactors from molybdoenzymes and in vitro reconstitution of nitrogenase and nitrate reductase. 14 98

Evidence for the formation of singlet oxygen during the oxidation of NADPH by liver microsomes is presented. The evidence is based primarily on the enzyme-dependent formation of dibenzoylethylene from diphenylfuran, a reaction which is specific for singlet oxygen. The apparent formation of singlet oxygen is coupled to the occurrence of peroxidation of microsomal lipid, a phenomenon known to be associated with NADPH oxidation by the particles. Both the peroxidation of lipid and the apparent formation of singlet oxygen are related to the amount of Fe3+ present in the system and the results are consistent with the possibility that the singlet oxygen formed by this system is derived from the breakdown of lipid peroxides. If 1O2 is formed from breakdown of lipid peroxides, it would be dependent on O-/-2 formation because superoxide anion has been shown to undergo reactions in this system which generate extremely reactive free radicals (probably hydroxyl) that initiate lipid peroxidation. These peroxides are quite unstable and their degradation may be the source of 1O2. We have consistently observed that O-/-2 itself is not a reactive radical with respect to lipids or radical scavengers. Hence, O-/-2 cannot be the radical which initiates lipid peroxidation on which 1O2 generation appears to depend. The results may offer at least part of the explanation for the dietary requirement for alpha-tocopherol which not only scavenges free radicals but quenches singlet oxygen as well. This report also includes description of studies indicating that another enzyme, xanthine oxidase, which forms superoxide anion during its activity under aerobic conditions, does not form singlet oxygen during its function. This finding is in contrast to reports of others which indicate that xanthine oxidase activity does produce 1O2.
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PMID:Singlet oxygen production associated with enzyme-catalyzed lipid peroxidation in liver microsomes. 16 47

In the presence of Fe-3+ and complexing anions, the peroxidation of unsaturated liver microsomal lipid in both intact microsomes and in a model system containing extracted microsomal lipid can be promoted by either NADPH and NADPH : cytochrome c reductase or by xanthine and xanthine oxidase. Erythrocuprein effectively inhibits the activity promoted by xanthine and xanthine oxidase but produces much less inhibition of NADPH-dependent peroxidation. The singlet-oxygen trapping agent, 1, 3-diphenylisobenzofuran, had no effect on NADPH-dependent peroxidation but strongly inhibited the peroxidation promoted by xanthine and xanthine oxidase. NADPH-dependent lipid peroxidation was also shown to be unaffected by hydroxyl radical scavengers.. The addition of catalase had no effect on NADPH-dependent lipid peroxidation, but it significantly increased the rate of malondialdehyde formation in the reaction promoted by xanthine and xanthine oxidase. The results demonstrate that NADPH-dependent lipid peroxidation is promoted by a reaction mechanism which does not involve either superoxide, singlet oxygen, HOOH, or the hydroxyl radical. It is concluded that NADPH-dependent lipid peroxidation is initiated by the reduction of Fe-3+ followed by the decomposition of hydroperoxides to generate alkoxyl radicals. The initiation reaction may involve some form of the perferryl ion or other metal ion species generated during oxidation of Fe-2+ by oxygen.
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PMID:The mechanism of liver microsomal lipid peroxidation. 23 6

A new method for the determination of guanase is described. Xanthine, the product of the guanase reaction, is oxidized by xanthine oxidase, forming uric acid and hydrogen peroxide. Hydrogen peroxide is further reduced to water by catalase in the presence of ethanol. The acetaldehyde formed in this reaction step is dehydrogenated NAD or NADP dependent by aldehyde dehydrogenase. The NADH or NADPH production is measured and utilized for the calculation of the guanase activity. The sensitivity of the method can be doubled by the addition of uricase, which oxidizes uric acid to permit the formation of another mole of hydrogen peroxide.
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PMID:A new spectrophotometric assay for enzymes of purine metabolism. II. Determination of guanase activity. 48 57

The mechanism of the inhibitory action of rebamipide, a new mucosal protective drug, was studied using rats with diethyldithiocarbamate-induced gastric antral ulcers. Rebamipide reduced ulcer formation and inhibited the elevation in lipid peroxide concentration in the gastric mucosa. Rebamipide inhibited both luminol- and lucigenin-dependent chemiluminescence of neutrophils activated by formyl-methionyl-leucyl-phenylalanine. Rebamipide did not alter the reduction of cytochrome c induced by the xanthine-xanthine oxidase system or the NADPH-dependent microsomal lipid peroxidation in the liver. These findings suggest that rebamipide prevents diethyldithiocarbamate-induced gastric ulcer formation by inhibiting neutrophil activation.
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PMID:Antiulcer mechanism of action of rebamipide, a novel antiulcer compound, on diethyldithiocarbamate-induced antral gastric ulcers in rats. 131 72

Picroliv, the active principle of Picrorhiza kurrooa, and its main components which are a mixture of the iridoid glycosides, picroside-I and kutkoside, were studied in vitro as potential scavengers of oxygen free radicals. The superoxide (O2-) anions generated in a xanthine-xanthine oxidase system, as measured in terms of uric acid formed and the reduction of nitroblue tetrazolium were shown to be suppressed by picroliv, picroside-I and kutkoside. Picroliv as well as both glycosides inhibited the non-enzymic generation of O2- anions in a phenazine methosulphate NADH system. Malonaldehyde (MDA) generation in rat liver microsomes as stimulated by both the ascorbate-Fe2+ and NADPH-ADP-Fe2+ systems was shown to be inhibited by the Picroliv glycosides. Known antioxidants tocopherol (vitamin E) and butylated hydroxyanisole (BHA) were also compared with regard to their antioxidant actions in the above system. It was found that BHA afforded protection against ascorbate-Fe(2+)-induced MDA formation in microsomes but did not interfere with enzymic or non-enzymic O2- anion generation; and tocopherol inhibited lipid peroxidation in microsomes by both prooxidant systems and the generation of O2- anions in the non-enzymic system but did not interfere with xanthine oxidase activity. The present study shows that picroliv, picroside-I and kutkoside possess the properties of antioxidants which appear to be mediated through activity like that of superoxide dismutase, metal ion chelators and xanthine oxidase inhibitors.
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PMID:Picroliv, picroside-I and kutkoside from Picrorhiza kurrooa are scavengers of superoxide anions. 132 26


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