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. 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.
J Biol Chem 1976 Sep 10
PMID:Ethanol metabolism by a transplantable hepatocellular carcinoma. Role of microsomes and mitochondria. 13 37

A 25-year-old white man with gout and nephropathy and with a previous reaction to allopurinol was given a trial dose of oxypurinol. He developed malaise, a generalized erythematous reaction with edema, pruritus, and emesis; this was clinically identical to the reaction he experienced with allopurinol. When the patient's lymphocytes were exposed in vitro to oxypurinol and allopurinol, increased DNA synthesis was observed, suggesting an immunologic basis for the reaction. This patient indicates that clinical cross reactivity to allopurinol and oxypurinol does occur and may be of an immunologic basis. There is a need for additional xanthine oxidase inhibitors for such patients.
Ann Intern Med 1976 Sep
PMID:Allergic reaction to allopurinol with cross-reactivity to oxypurinol. 13 55

This report describes studies yielding additional evidence that superoxide anion (O2) production by some biological oxidoreductase systems is a potential source of hydroxyl radical production. The phenomenon appears to be an intrinsic property of certain enzyme systems which produce superoxide and H2O2, and can result in extensive oxidative degradation of membrane lipids. Earlier studies had suggested that iron (chelated to maintain solubility) augmented production of the hydroxyl radical in such systems according to the following reaction sequence: O2 + Fe3+ leads to O2 + Fe2+ Fe2+ + H2O2 leads to Fe3+ + HO-+OH-. The data reported below provide additional support for the occurrence of these reactions, especially the reduction of Fe3+ by superoxide. Because the conditions for such reactions appear to exist in animal tissues, the results indicate a mechanism for the initiation and promotion of peroxidative attacks on membrane lipids and also suggest that the role of antioxidants in intracellular metabolism may be to inhibit initiation of degradative reactions by the highly reactive radicals formed extraneously during metabolic activity. This report presents the following new information: (1) Fe3+ is reduced to Fe2+ during xanthine oxidase activity and a significant part of the reduction was oxygen dependent. (2) Mn2+ appears to function as an efficient superoxide anion scavenger, and this function can be inhibited by EDTA. (3) The O2-dependent reduction of Fe3+ to Fe2+ by xanthine oxidase activity is inhibited by Mn2+, which, in view of statement 2 above, is a further indication that the reduction of the iron involves superoxide anion. (4) Free radical scavengers prevent or reverse the Fe3+ inhibiton of cytochrome c3+ reduction by xanthine oxidase. (5) The inhibition of xanthine oxidase-catalyzed reduction of cyt c3+ by Fe3+ does not affect uric acid production by the xanthine oxidase system. (6) The reoxidation of reduced cyt c in the xanthine oxidase system is markedly enhanced by Fe3+ and is apparently due to enhanced HO-RADICAL formation since the Fe3+-stimulated reoxidation is inhibited by free radical scavengers, including those with specificity for the hydroxyl radical.
Chem Biol Interact 1976 Sep
PMID:Evidence for superoxide-dependent reduction of Fe3+ and its role in enzyme-generated hydroxyl radical formation. 18 3

The developmental patterns of enzyme activities related to GMP metabolism have been investigated in chick embryo musculus complexus (m. Complexus). Guanylate phosphatase activity increases conspicuously from 18th to 21st day, guanosine phosphorylase increases on the 21st day and the guanase shows a very low activity during the whole period considered. Xanthine oxidase was always found absent. The results suggest that during the first period of incubation GMP breakdown in chick embryo m. complexus might follow a catabolic pathway, while starting from the 18th day some guanine might be converted to GMP originating a new metabolic pathway as previously suggested for AMP metabolism.
Boll Soc Ital Biol Sper 1979 Sep 30
PMID:[Enzymes of purine metabolism in the nuchal muscle (M. complexus) of chick embryo]. 23 42

Methods for measuring enzymatic activity of adenosine deaminase from human erythrocytes were examined and compared with each other. Determination of ADA by the method in which adenosine is converted into inosine with uric acid as the final product by the action of nucleoside phosphorylase and xanthine oxidase appears to yield the most reliable results. In the recommended assay saponin is used for lysis of erythrocytes when testing adenosine deaminase activity in red blood cells. Storage of erythrocyte samples is optimal at +4 degrees C; storage at room temperature or at -20 degrees C leads to loss of adenosine deaminase activity.
Clin Chim Acta 1975 Sep 16
PMID:Quantitative measurement of adenosine deaminase from human erythrocytes. 24 May 21

The fluorescent nucleotide analogues (the 5'-mono-, di-, and triphosphates of lin-benzoguanosine, lin-benzoxanthosine, and lin-benzoinosine) have been prepared for use as dimensional probes of enzyme binding sites. They have quantum yields in aqueous solution of 0.39, 0.55, and 0.04 and fluorescent lifetimes of 6, 9, and approximately equal to 1.5 nsec, respectively. lin-Benzoinosine 5'-monophosphate is a substrate for xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2), providing lin-benzoxanthosine 5'-monophosphate, and lin-benzoinosine 5'-diphosphate is a substrate for polynucleotide phosphorylase (polyribonucleotide:orthophosphate nucleotidyltransferase. EC 2.7.7.8), giving poly(lin-benzoinosinic acid). The benzologues of the purine diphosphates are substrates for pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40), which is used to prepare the triphosphates.
Proc Natl Acad Sci U S A 1979 Sep
PMID:Synthesis of fluorescent nucleotide analogues: 5'-mono-, di-, and triphosphates of linear-benzoguanosine, linear-benzoinosine, and linear-benzoxanthosine. 29 62

Xanthine dehydrogenase engaged in catalyzing the oxidation of substrate by oxygen is repidly inactivated by the hydrogen peroxide generated during the reaction. Experimental evidence shows that peroxide reacts more readily with the reduced than with the oxidized form of the enzyme. Inactivation results from modification of the cyanolysable sulfur present at the molybdenum center.
J Biol Chem 1979 Sep 25
PMID:Syncatalytic modification of chicken liver xanthine dehydrogenase by hydrogen peroxide. The nature of the reaction. 47 63

1. All available N-mono- and N,N'-dimethylallopurinols and the corresponding 4-thioxo derivatives have been tested as substrates or inhibitors of bovine milk xanthine oxidase (xanthine: oxygen oxidoreductase, EC 1.2.3.2). 2. None of the compounds tested revealed any inhibitory activity towards the enzyme. 3. All compounds were resistant to enzymic oxidation, with the exception of 7-methylallopurinol and its 4-thioxo analog. Both these compounds were attacked at position 6. 7-Methylallopurinol was oxidised nearly ten times faster than the isomeric 3-methylhypoxanthine. 4. These observations can be explained by assuming that for attack at C-6, the enzyme must bind both to N-1 and N-2 in the pyrazole ring and causes tautomerisation, which places a double bond at position 5,6 in the pyrimidine ring. This activation process resembles the activation of hypoxanthine.
Biochim Biophys Acta 1979 Sep 12
PMID:Behavior of N-methylated allopurinols and related 4-thioxopyrazolo [3,4-d]pyrimidines towards bovine milk xanthine oxidase. 48 4

The synthesis of 1H-pyrrolo[3,2-c]pyridine-4,6(5H,7H)-dione (3,7-dideazaxanthine) (1), 5-methyl-1H-pyrrolo-[3,2-c]pyridine-4,6(5H,7H)-dione (1-methyl-3,7-dideazaxanthine) (2), and 1,7-dihydropyrano[4,3-b]pyrrole-4,6-dione (1-oxa-1,3,7-trideazaxanthine) (3) has been accomplished from 3-alkoxycarbonylpyrrole-2-acetates (4, 11, and 12 for 1 and 2) and from 3-carboxypyrrole-2-acetic acid (6 for 3). Compounds 1 and 2 have been found to be weak inhibitors of the noncompetitive type for xanthine oxidase while 3 showed no inhibitory properties toward this enzyme.
J Med Chem 1978 Sep
PMID:Synthesis and xanthine oxidase inhibitory analysis of 1H-pyrrolo[3,2-c]pyridine-4,6(5H,7H)-dione (3,7-dideazaxanthine) and two of its derivatives. 72 64

3,5-Bis(4-pyridyl)-1,2,4-triazole (PPT), 3-(4-pyrimidinyl)-5-(4-pyridyl)-1,2,4-triazole (PMPT), and 3-(4-pyridazinyl)-5-(4-pyridyl)-1,2,4-triazole (PZPT) are among the most active competitive inhibitors of xanthine oxidase among a series of 3,5-disubstituted triazoles synthesized for this purpose, inhibition constants being less than 1 times 10(-7) M for each. ED50 values in squirrel monkeys derived from first-order rate constants for the first and rate-limiting step of the sequence, xanthine leads to uric acid leads to allantoin plus CO2, range from 0.04 to 0.08 mg kg-1 orally, with unusually long durations of action attributable to asymmetric distribution of inhibitor within liver and gut as a consequence of enterohepatic recirculation. Sensitivity of rats, dogs, and anthropoid species to these, as to other xanthine oxidase inhibitors, is markedly less than that of the squirrel monkey, but the triazoles are at least an order of magnitude more active than the representative purine analogs tested.
J Med Chem 1975 Sep
PMID:3,5-disubstituted 1,2,3,4-triazoles, 1 new class of xanthine oxidase inhibitor. 80 13


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