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)

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

The relationship between allopurinol oxidizing enzyme and aldehyde oxidase was investaged in mice. The oxidation of both N-methylnicotinamide and allopurinol appears to be catalized by a single enzyme, aldehyde oxidase (aldehyde-oxygen oxidoreductase EC, 1.2.3.1.). This conclusion is based on the following evidence; The postnatal changes of allopurinol and N-methylnicotinamide oxidizing activities were similar during growth and the levels of both activities increased in a parallel fashion upon the attainment of sexual maturity. The rates of loss of the activities of both enzymes by heat denaturation as well as dexamethasone administration were similar. The inhibitors of allopurinol oxidizing enzyme also suppressed N-methylnicotinamide oxidation. Competition of N-methylnicotineamide and allopurinol for oxidation was demonstrated. The rate of increase of the activities in both enzymes was almost parallel during each step of the purification from mouse liver supernatant. It was ascertained that xanthine oxidase in the enzyme preparation does not influence allopurinol oxidation.
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PMID:[Hepatic allopurinol oxidizing enzyme in mice]. 12 99

The syntheses of a number of 2-substituted 4-trifluoromethylimidazoles and 3-substituted 5-(4-pyridyl)-1,2,4-triazoles are described. The trifluoromethylimidazoles were prepared from 3,3-dibromo-1,1,1-trifluoroacetone after hydrolysis with aqueous sodium acetate solution and condensation with an aldehyde in the presence of ammonia. Basic hydrolysis of the trifluoromethyl group was found to provide a facile method for the synthesis of imidazole-4-carboxylic acids. In the imidazole series a 2-aryl substituent and a free imino group were required for xanthine oxidase inhibitory activity. The triazoles were obtained through the reaction of an aroylhydrazine and an imino ether followed by thermal ring closure of the intermediate acylamidrazone. As in the imidazole series, a free imino group is an absolute requirement for in vitro activity. Additional structure-activity relationships of these compounds are presented.
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PMID:4-Trifluoromethylimidazoles and 5-(4-pyridyl)-1,2,4-triazoles, new classes of xanthine oxidase inhibitors. 117 86

Ultraweak chemiluminescence (CL) from bilirubin occurs in the presence of triplet oxygen and is stimulated by the addition of aldehydes. Active oxygen species also enhance bilirubin CL, in the absence of aldehydes. An inhibitory effect of active oxygen scavengers on the CL indicated that active oxygens generated from the decomposition of added hydrogen peroxide or from the xanthine-xanthine oxidase reaction contributed to the CL from bilirubin molecules. However, the contribution of singlet oxygen to the CL disappeared in the presence of formaldehyde. This suggested that the scission of tetrapyrrole bonds via a dioxetane intermediate or the production of triplet carbonyls from the oxidation of aldehydes by singlet oxygen was not involved in the CL, at least in the presence of formaldehyde. The spectrum of CL induced by the generation of active oxygen was the same as that from the aldehyde-enhanced CL reaction. We propose that the formation of a hydroperoxide (and/or hydroxide) bilirubin intermediate, but not a dioxetane, may be involved in the excitation of bilirubin molecules for CL.
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PMID:Bilirubin chemiluminescence induced by the attack of active oxygen species. 132 33

Free radical generation and catalytic iron have been implicated in the pathogenesis of alcohol-induced liver injury but the source of free radicals is a subject of controversy. The mechanism of ethanol-induced liver injury was investigated in isolated hepatocytes from a rodent model of iron loading in which free radical generation was measured by the determination of alkane production (ethane and pentane). Iron loading (125 mg/kg i.p.) increased hepatic non-heme iron 3-fold, increased the prooxidant activity of cytosolic ultrafiltrates 2-fold and doubled ethanol-induced alkane production. The addition of desferrioxamine (20 microM), a tight chelator of iron, completely abolished alkane production indicating the importance of catalytic iron. The role of cellular oxidases as a source of ethanol induced free radicals was studied through the use of selective inhibitors. In both the presence and absence of iron loading, selective inhibition of xanthine oxidase with oxipurinol(20 microM) diminished ethanol-induced alkane production 0-40%, inhibition of aldehyde oxidase with menadione (20 microM) diminished alkane production 36-75%, while the inhibition of aldehyde and xanthine oxidase by feeding tungstate (100 mg/kg/day) virtually abolished alkane production. Addition of acetaldehyde(50 microM) to hepatocytes generated alkanes at rates comparable to those achieved with ethanol indicating the importance of acetaldehyde metabolism in free radical generation. The cellular oxidases (aldehyde and xanthine oxidase) along with catalytic iron play a fundamental role in the pathogenesis of free radical injury due to ethanol.
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PMID:The role of cellular oxidases and catalytic iron in the pathogenesis of ethanol-induced liver injury. 160 88

This paper describes a new approach to the histochemical demonstration of superoxide generation by pulmonary vascular endothelial cells using a supravital high manganese/diamine technique, in which nascent superoxide radicals induce formation of amber, osmiophilic polymers of diaminobenzidine (DAB), detectable by light or electron microscopy. Superoxide oxidizes Mn2+ ions to the Mn3+ valence state. In turn trivalent manganese readily initiates formation of the polymerized DAB reaction product. Isolated rat lungs were perfused in situ with bloodless, buffered high manganese/DAB salt solution via the pulmonary artery. The aortic root was ligated to minimize outflow from the left heart, so that perfusate shunted across pulmonary capillary endothelium, to fill the alveolar spaces and drain via the trachea. Lungs were perfused for 3 min with oxygen equilibrated buffer, with or without 60 min prior warm anoxia, induced by initial perfusion with argon sparged buffer. After aldehyde fixation and tissue processing DAB reaction product was detected on the inner, luminal surface of the vascular endothelium by both light and electron microscopy. Bronchi and epithelial cells never stained positively. The histochemical reaction was absent or markedly reduced in non-manganese treated or superoxide dismutase treated lungs, as well as in lungs perfused with calcium free buffer. The histochemical reaction was not prevented by the xanthine oxidase inhibitors allopurinol or methylene blue. The high manganese/diamine technique provides direct visual evidence of a calcium dependent mechanism by which pulmonary vascular endothelial cells can generate superoxide radicals.
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PMID:Endothelial superoxide production in buffer perfused rat lungs, demonstrated by a new histochemical technique. 165 43

Acetaldehyde (AA), the first product of ethanol metabolism, has been suggested as an important mediator in alcoholic pancreatitis, but experimental evidence has not been convincing. Prior work using the isolated perfused canine pancreas preparation has suggested that toxic oxygen metabolites generated by xanthine oxidase (XO) may mediate the early injury in pancreatitis. Xanthine oxidase is capable of oxidizing AA, and during this oxidation free radicals are released. The hypothesis that acute alcoholic pancreatitis may be initiated by AA in the presence of active XO (converted from xanthine dehydrogenase [XD]) was tested in the authors' experimental preparation by converting XD to XO by a period of ischemia, and infusing AA. Control preparations remained normal throughout the 4-hour perfusion (weight gain, 7 +/- 4 g; amylase activity, 1162 +/- 202 U/dL). One hour of ischemia or infusion of AA at 25 mg/hr or at 50 mg/hr without ischemia did not induce changes in the preparation. Acetaldehyde at 250 mg/hr induced minimal edema and weight gain (16 +/- 4 g; p less than 0.05), but not significant hyperamylasemia. Changes also were not observed when 1-hour ischemia was followed by a bolus of ethanol (1.5 g) or sodium acetate (3.0 g), or by infusion of 25 mg/hr of AA. One hour of ischemia followed by infusion of AA at 50 mg/hr or at 250 mg/hr induced edema, hemorrhage, weight gain (22 +/- 7 g [p less than 0.05] and 26 +/- 17 g [p less than 0.05]) and hyperamylasemia (2249 +/- 1034 U/dL [p less than 0.05] and 2602 +/- 1412 U/dL [p less than 0.05]). Moreover infusion of AA at 250 mg/hr after 2 hours of ischemia potentiated the weight gain (62 +/- 20 g versus 30 +/- 14 g [p less than 0.05]), but not the hyperamylasemia (3404 +/- 589 U/dL versus 2862 +/- 1525 U/dL) as compared with 2 hours of ischemia alone. Pancreatitis induced by 1 hour of ischemia followed by AA at 50 mg/hr could be inhibited by pretreatment with the free radical scavengers superoxide dismutase and catalase and ameliorated with the XO inhibitor allopurinol. The authors conclude that AA, in the presence of active XO, can initiate acute pancreatitis in the isolated canine pancreas preparation and may be important in the initiation of acute alcoholic pancreatitis in man. Toxic oxygen metabolites appear to play an important intermediary role.
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PMID:The role of acetaldehyde in the pathogenesis of acute alcoholic pancreatitis. 172 Jun 11

IN vitro peroxidation by air, or xanthine-xanthine oxidase (xanthine-XOD) was performed to estimate the production of aliphatic aldehydes from free polyunsaturated fatty acids (PUFA), triglycerides, phospholipids and rat liver microsomes and mitochondria. The aldehyde contents in peroxidized lipids were determined by liquid chromatography and fluorescence detection. In both peroxidation, pentanal, (E)-4-hydroxy-2-nonenal (4-HN), and hexanal were produced from omega-6 PUFA rich lipids and propanal was markedly enhanced by increasing the degree of fatty acid unsaturation. The ratios of 4-HN to hexanal production in xanthine-XOD peroxidation of the omega-6 PUFA rich lipids, and rat liver microsomes and mitochondria were much higher than those in air peroxidation. The ratios (4-HN/hexanal) obtained in microsomes and mitochondria by xanthine-XOD were similar to those in rat liver observed in vitamin E deficient studies. The determination of these aldehydes may be useful to estimate the kinds of fatty acids peroxidized and investigate in vivo lipid peroxidation mechanism.
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PMID:Production of aliphatic aldehydes on peroxidation of various types of lipids. 177 32

NAD(P)-linked aldehyde dehydrogenases catalyze the oxidation of a wide variety of aldehydes. Thirteen of these enzymes have been identified in mouse tissues; eleven are found in the liver. Some are substrate-nonspecific; others are relatively substrate-specific. The present investigation sought to determine which of these enzymes are operative in catalyzing the oxidation of retinaldehyde to retinoic acid, a metabolite of vitamin A that promotes the differentiation of epithelial and other cells. Spectrophotometric and HPLC assays were used for this purpose. Enzyme-catalyzed oxidation of retinaldehyde (25 microM) was restricted to the cytosol (105,000 g supernatant fraction) and occurred at a rate of 211 nmol/min/g liver; oxidation of acetaldehyde (4 mM) by this fraction proceeds about ten times faster. At least 90% of this activity was NAD dependent. Of the approximately 10% that was apparently NAD independent, two-thirds was inhibited by 1 mM pyridoxal, a known inhibitor of aldehyde oxidase. Of the six cytosolic aldehyde dehydrogenases, only two, viz. AHD-2 and AHD-7, catalyzed the oxidation of retinaldehyde to retinoic acid. An additional NAD-dependent enzyme, viz. xanthine oxidase (dehydrogenase form), also catalyzed the reaction. Catalysis by AHD-2 accounted for more than 90% of the total NAD-dependent activity. Km values were 0.7, 0.6 and 0.9 microM, respectively, for the AHD-2-, AHD-7- and xanthine oxidase (dehydrogenase form)-catalyzed reaction. AHD-4, an aldehyde dehydrogenase found in the cytosol of mouse stomach epithelium and cornea, did not catalyze the reaction.
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PMID:Identification of mouse liver aldehyde dehydrogenases that catalyze the oxidation of retinaldehyde to retinoic acid. 188 36

Exposure of human lymphocyte cultures to superoxide generated by the xanthine-xanthine oxidase (X-XO) system, resulted in formation of a clastogenic factor (CF), as expected from previous work. We speculated that arachidonic acid (AA), the major polyunsaturated fatty acid of biological membranes, was oxidized via the cyclooxygenase-lipoxygenase pathways or nonenzymatically by oxygen free radicals in the culture medium to products with clastogenic properties. In the present study, we analyzed CF for AA-derived products and tested corresponding commercial standards for their clastogenic properties. The results show that prostaglandins, thromboxane, and H(P)ETEs were not increased in supernatants from X-XO treated cultures compared to untreated cultures. Synthetic H(P)ETEs added to the medium of lymphocyte cultures were only slightly or not clastogenic. In contrast hereto, the degradation product 4-hydroxynonenal was found in 50% of CF samples, while it was absent in all 43 control samples. The kinetics of detectability in the culture medium was similar to that of CF. Also, the clastogenic effect of synthetic 4-hydroxynonenal at concentrations as low as 0.1 microM suggested that this aldehyde, known for its genotoxic effects, was a clastogenic component of CF. The indirect action mechanisms of 4-hydroxynonenal via inactivation of functional SH groups in DNA polymerases, may explain why chromatid-type damage is predominant in lymphocytes exposed to CF in the Go-G1 phase of the cell cycle. This particularly was already stressed 20 years ago in the first observations of radiation-induced CF. However, 4-hydroxynonenal is not the only clastogenic component of CF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hydroxynonenal, a component of clastogenic factors? 190 88


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