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)

1. Isoquinoline, cinnoline, quinoxaline, quinazoline and phthalazine were incubated with preparations of rabbit liver aldehyde oxidase. 2. The oxidation products, 1-hydroxyisoquinoline, 4-hydroxycinnoline, 2-hydroxy- and 2,3-dihydroxy-quinoxaline, 4-hydroxy- and 2,4-dihydroxy-quinazoline, and 1-hydroxyphthalazine were identified by comparison of their spectral and chromatographic characteristics with those of authentic compounds. 3. Michaelis-Menten constants are reported for the action of the parent heterocycles with aldehyde oxidase. The compounds reported in this study are among the most efficient substrates yet described for rabbit liver aldehyde oxidase. 4. The compounds in 1 above were incubated with bovine milk xanthine oxidase: only quinazoline and phthalazine yielded significant amounts of metabolites. Km values were calculated for these compounds. 5. Incubation of the heterocycles with rat liver preparations gave qualitatively the same results as those obtained using rabbit liver, but smaller amounts of the oxidation products were detected from rat liver incubations.
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PMID:The oxidation of azaheterocycles with mammalian liver aldehyde oxidase. 51 90

1. Twenty-six strains of mice were surveyed by starch gel electrophoresis for genetic variation of four liver enzymes; aldehyde dehydrogenase, aldehyde oxidase, xanthine oxidase and formaldehyde dehydrogenase. 2. A variant of aldehyde dehydrogenase was found in strains ICFW, IS/Cam, NZB, NZW, Simpson and Schneider. A variant of aldehyde oxidase was found in CE. A possible variant of xanthine oxidase was found in SF/Cam. 3. The gene determining the electrophoretic variant of aldehyde oxidase is either the same as, or very closely linked to, the Aox gene which determines aldehyde oxidase activity.
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PMID:Genetic variation of some aldehyde-oxidizing enzymes in the mouse. 74 39

Tissue distribution and levels of allopurinol oxidizing enzyme and xanthine oxidase with hypoxanthine as a substrate were compared with supernatant fractions from various tissues of mice and from liver of mice, rats, guinea pigs and rabbits. The allopurinol oxidizing enzyme activities in liver were quite different among the species and the sex difference of the enzyme activity only in mouse liver. In mice, the highest activity of allopurinol oxidizing enzyme was found in the liver with a trace value in lung, but the enzyme activity was not detected in brain, small intestine and kidney, while the highest activity of xanthine oxidase was detected in small intestine, lung, liver and kidney in that sequence. The allopurinol oxidizing enzyme activity in mouse liver supernatant fraction did not change after storage at -20 degrees C or dialysis against 0.1 M Tris-HCl containing 1.15% KCl, but the activity markedly decreased after dialysis against 0.1 M Tris-HCl. On the contrary, the xanthine oxidase was activated 2 to 3 times the usual activity after storage at -20 degrees C or dialysis of the enzyme preparation. These results indicated that allopurinol was hydroxylated to oxipurinol mainly by the enzyme which is not identical to xanthine oxidase in vivo. A possible role of aldehyde oxidase involved in the allopurinol oxidation in liver supernatant fraction was dicussed.
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PMID:Tissue distribution and characteristics of xanthine oxidase and allopurinol oxidizing enzyme. 102 7

The metabolism of 8-14C-theophylline (14C-Theo) was investigated in vivo and in vitro in the rat. In vivo, 14C-Theo at an initial blood concentration of 10muM was metabolized to at least two different metabolites, 1,3-dimethyl uric acid and 1-methyl uric acid. The biological half-life of the 8-14C-Theo (6 +/- 1.5 hours) was determined from the urinary excretion of radioactivity. Ten days of oral pretreatment of rats with theophylline resulted in a faster rate of metabolism of both 14C-Theo and zoxazolamine. In vitro metabolism of 14C-Theo was investigated in order to identify the enzyme(s) responsible for theophylline metabolism. A tissue survey utilizing tissue slices demonstrated that the metabolism is localized only in the liver since slices of heart, lung, intestine, brain, adrenals, kidney or spleen did not metabolize 14C-Theo. 14C-Theo metabolism in the liver was localized in the subcellular fraction of microsomes and not in the mitochondria or cytosol. 14C-Theo metabolism by liver slices or liver microsomes was inhibited by typical liver microsomal inhibitors such as 2-diethylaminoethyl-2,2-diphenylvalerate (SKF 525-A) and 3-methyl-4-methylaminoazobenzene. 14C-Theo metabolism in liver slices was increased by the liver microsomal-inducing agents, phenobarbital and 3-methylcholanthrene. 3-Methylcholanthrene also increased 14C-Theo metabolism by the liver microsomal fraction. One of the metabolites, 1-methylxanthine, generated by the microsomal system, is a substrate for xanthine oxidase, and its conversion to 1-methyl uric acid by xanthine oxidase was blocked by allopurinol. 14C-Theo per se was shown not to be a substrate for liver xanthine oxidase or aldehyde oxidase. These results indicate that Theo per se is metabolized by the liver microsomal system and not by liver xanthine oxidase or aldehyde oxidase.
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PMID:Theophylline metabolism by the rat liver microsomal system. 124 12

1. Enzyme systems responsible for formation of cyclopropane ring-cleavage metabolites (M1 and M2) of illudin S in rat liver were characterized. 2. The enzymes were localized in the cytosol fraction and utilized NADPH alone as electron donor; they were not affected by oxygen and had low pH optima. 3. Formation of metabolites M1 and M2 was inhibited completely by dicumarol (10(-4) M), an inhibitor of DT-diaphorase. 4. Menadione (10(-4) M) and quercetin (10(-4) M) both inhibited formation of M1 and M2 by 35% and 15%, respectively, but quinacrine, barbital, pyrazole and p-chloromercuribenzoic acid had no significant effect. 5. Results show that the enzyme systems may differ from DT-diaphorase, aldehyde oxidase, xanthine oxidase, ketone reductase, aldose reductase, aldehyde reductase and alcohol dehydrogenase, known cytosolic enzymes responsible for xenobiotic metabolism.
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PMID:Metabolism by rat liver cytosol of illudin S, a toxic substance of Lampteromyces japonicus. II. Characterization of illudin S-metabolizing enzyme. 137 39

The reactivities with an excess of 5-5'-dithiobis (2-nitrobenzoic) acid (DTNB) of sulphydryl residues present in xanthine oxidase and aldehyde oxidase were studied and compared. The results show that two classes of sulphydryl groups with quite different reactivities exist in both enzymes either native or denatured. Some of the available sulphydryl residues thus react instantaneously with the DTNB, whereas the others react very slowly following pseudo-first-order kinetics. The number of sulphydryl residues of each class and the rate constant of slowly reacting groups are, respectively, 1.7 and 0.8 in native xanthine oxidase and 1.6 and 1.7 in native aldehyde oxidase. In denatured enzymes, the number of fast- and slow-reacting sulphydryl residues obtained are, respectively, 13.9 and 7.9 in xanthine oxidase and 5.7 and 5.4 in aldehyde oxidase. Analogously, the rate constant for the slowly reacting groups is similar for the two native enzymes, but in denatured aldehyde oxidase it is double that of denatured xanthine oxidase.
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PMID:The molybdoenzymes xanthine oxidase and aldehyde oxidase contain fast- and slow-DTNB reacting sulphydryl groups. 144 1

Benznidazole (Bz) (N-benzyl-2-nitro-1-imidazole acetamide) is a drug used against Chagas' disease, a parasitic disease afflicting several millions of Latin Americans. Bz administration to Sprague-Dawley male rats at 100 mg/kg p.o. caused subcellular alterations in the adrenal cortex involving fasciculata and reticularis zones but not in the glomerulosa. There is Bz nitroreductase activity in the adrenal microsomal and mitochondrial fractions but most of it is localized in mitochondria. Activity in the two fractions requires NADPH under anaerobic conditions. Mitochondrial Bz nitroreductase activity was inhibited by oxygen. A minor but statistically significant inhibition was observed in mixtures incubated under carbon monoxide. Microsomal Bz nitroreductase activity was not detected under oxygen atmosphere and was not inhibited under carbon monoxide. No Bz nitroreductase activity mediated by xanthine oxidase or aldehyde oxidase was detected in the cytosolic fraction from rat adrenals. Electron microscopic examination of the adrenal cortex from Bz-treated animals revealed cells with marked lipid accumulation and alterations in nuclei, endoplasmic reticulum and mitochondria in the reticularis and fasciculata zones. In vitro results suggest a Bz nitroreductive activation, with minor or null P-450 participation, leading to reactive metabolites able to cause damage in various organelles.
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PMID:Benznidazole-induced ultrastructural alterations in rat adrenal cortex. Mechanistic studies. 151 44

Molybdenum hydroxylase activity in guinea pig liver has been compared with that of marker enzymes in mitochondria (succinate dehydrogenase), microsomes (glucose-6-phosphatase) and cytosol (lactate dehydrogenase). Aldehyde oxidase activity was highest in the cytosol, with about 10-fold activity of xanthine oxidase. Significant molybdenum hydroxylase activity was found in mitochondria with minimal levels in microsomes. Mitochondrial and cytosolic aldehyde oxidase varied in substrate specificity and electrophoretic mobility with two major bands in each fraction, one of which was common to cytosol and mitochondria.
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PMID:Subcellular localisation of guinea pig hepatic molybdenum hydroxylases. 159 89

5-Iodo-2-pyrimidinone-2'-deoxyribose (IPdR) can be converted into 5-iodo-deoxyuridine (IUdR), a clinical radiosensitizer, by aldehyde oxidase in the liver. This conversion does not require exogenous cofactors and cannot be catalyzed by mixed-function oxidases, xanthine oxidase or many other oxido-reductases. This "IPdR oxidase" activity is enriched in the liver; thus, extensive conversion of IPdR to IUdR could be anticipated in the liver and the therapeutic index of IPdR could be better than that of IUdR as a radiosensitizer for primary liver cancers or tumors metastasized to the liver. Based on structure and activity relationship studies, nucleoside analogues which could be activated by this enzyme to compounds capable of inhibiting DNA synthesis could be designed and should be explored as agents against cancer, viruses or parasites in the liver.
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PMID:Conversion of 5-iodo-2-pyrimidinone-2'-deoxyribose to 5-iodo-deoxyuridine by aldehyde oxidase. Implication in hepatotropic drug design. 159 12

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


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