Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A sensitive peroxyoxalate chemiluminescent (PO-CL) assay for activities of oxidases (uricase, choline oxidase, cholesterol oxidase and xanthine oxidase) which catalyse a formation of hydrogen peroxide was developed using 4,4'-oxalyl- bis[(trifluoromethyl-sulphonyl)imino]trimethylene-bis(4- methylmorpholinium)trifluoromethanesulphonate as a chemiluminogenic reagent and 2,4,6,8-tetramorpholinopyrimido[5,4- d]pyrimidine as fluorophore. The standard curve for hydrogen peroxide was linear over the range 1 x 10(-7)-1 x 10(-4) mol/L. Relative standard deviations for oxidase assays were 5.1-12.7% (n = 10). Detection limits were 1 x 10(-3) U/mL for uricase, 5 x 10(-4) U/mL for choline oxidase, 5 x 10(-3) U/mL for cholesterol oxidase and 5 x 10(-4) U/mL xanthine oxidase (sample to blank ratio, 3).
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PMID:Peroxyoxalate chemiluminescent assay for oxidase activities based on detecting enzymatically formed hydrogen peroxide. 767 61

Experiments in piglets indicate that the catabolic metabolism of purines is only developed during the first 4 weeks of life. During this time the catalytic activity of uricase in liver homogenates is increased about 5.5 fold (p < 0.01). The counts of uricase-carrying peroxisomes and cores are increased to a similar degree (p < 0.01). In the same time the catalytic activity of cytosolic xanthine oxidase is elevated about 4.6 fold (p < 0.01), mainly in the second and third week. In blood plasma uric acid is decreased from 19 to 12 molar % during weeks 1 to 4, hypoxanthine, xanthine and allantoin remain relatively constant. In urine xanthine and uric acid are decreased, hypoxanthine and allantoin are increased. At the age of 2-3 days a decrease of ambient temperature from 32 to 20 degrees C caused an increase of the plasma pool (p < 0.01) and turnover (p < 0.05) of uric acid. Pool size and turnover of hypoxanthine are only slightly elevated. The results are discussed in view of the slow development of hepatic enzymes, the increase of uric acid pool at lowered ambient temperature and causal events leading to urate nephropathia.
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PMID:[The postnatal development of porcine purine catabolism and the effect of the environmental temperature on turnover]. 823 73

We investigated the xanthine oxidase/xanthine dehydrogenase inhibitory activity and hypouricemic effect of a newly synthesized xanthine oxidase/xanthine dehydrogenase inhibitor, TEI-6720, 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazole-carboxylic acid, and compared its effects with those of allopurinol in rodents. TEI-6720 was found to inhibit bovine milk xanthine oxidase, and mouse liver and rat liver xanthine oxidase/xanthine dehydrogenase with IC50 values of 1.4, 1.8 and 2.2 nM, respectively. On bovine milk xanthine oxidase, TEI-6720 exhibited mixed-type inhibition and the Ki value was 0.7 nM. TEI-6720 displayed prolonged urate-lowering activity in normal mice and rats. We evaluated the hypouricemic effect of TEI-6720 on hyperuricemia induced by the uricase inhibitor, potassium oxonate (250 mg/kg s.c., 1 h before the test drugs), and measured the total molarity of both serum allantoin and urate in rats. Oral TEI-6720 and allopurinol had a hypouricemic effect 2 h after their administration to oxonate-pretreated rats with ED50 values of 1.5 and 5.0 mg/kg, respectively. Both compounds also reduced the combined molarity of uric acid and allantoin in rats. The ED50 values of TEI-6720 and allopurinol were 2.1 and 6.9 mg/kg p.o., respectively. These results suggest that TEI-6720 may be useful for the treatment of hyperuricemia.
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PMID:Hypouricemic effect of the novel xanthine oxidase inhibitor, TEI-6720, in rodents. 824 54

The rise in plasma uric acid (UA) in chronic renal failure (CRF) is quite limited. This may be due to either increased extrarenal excretion, diminished biosynthesis, and/or enhanced degradation of uric acid. The intestinal flux studies revealed a striking modification of urate transport from no net flux to a net secretory flux in the jejunum and from a basal net absorptive to a net secretory flux in the colon of CRF animals. In addition, CRF animals showed a marked reduction in hepatic, renal, and enteric tissue xanthine oxidase activity and no significant change in tissue uricase activity. The correction of anemia with erythropoietin did not significantly alter the plasma concentration or urinary excretion of urate. Thus, enhanced enteric excretion and depressed production of uric acid (reduced xanthine oxidase activity) may account for the lack of significant hyperuricemia in CRF.
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PMID:Effect of chronic experimental renal insufficiency on urate metabolism. 858 4

Various tissues of the marine bivalve Mytilus galloprovincialis were analysed histochemically for oxidases capable of generating reactive oxygen species (ROS) using the cerium-DAB technique. Incubations were performed on unfixed cryostat sections using polyvinyl alcohol and semipermeable membranes. High xanthine oxidoreductase and D-amino acid oxidase (DAOX) activities were observed in kidney epithelial cells of mussels. DAOX also presented a strong activity in all the digestive epithelia. No xanthine oxidase activity was observed in any of the mussel tissues tested suggesting the presence of an enzyme only showing dehydrogenase activity. Mannitol oxidase, associated with special organelles called 'mannosomes' of terrestrial gastropods, presented a weak activity in the stomach epithelium and a strong specific activity in the haemocytes. Only DAOX presented a discrete granular distribution compatible with a peroxisomal compartmentalization. No urate oxidase activity could be demonstrated in tissues of mussels. These observations suggest a role for peroxisomes in ROS generation and determine the tissues capable of producing oxygen radicals in the digestive gland. This study raises the question of the behaviour of these enzymes in conditions in which ROS-generating organic xenobiotics are accumulated in the digestive gland of molluscs.
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PMID:Histochemistry of oxidases in several tissues of bivalve molluscs. 957 Aug 92

Acute tumour lysis syndrome (ATLS) is a metabolic derangement (hyperuricaemia, hyperphosphataemia, hyperkalaemia and hypocalcaemia) associated with lymphoproliferative malignancies. The nature and severity of the metabolic alterations are variable. Major complications are oliguric acute renal failure and delays in initiating chemotherapy. Current management of ATLS includes hydration, alkalinization, diuretics, when indicated, and the reduction of uric acid levels using allopurinol or urate oxidase. Allopurinol inhibits xanthine oxidase, an enzyme that catalyses the conversion of hypoxanthine and xanthine to uric acid. Urate oxidase (Uricozyme), a naturally occurring proteolytic enzyme in many mammals, degrades uric acid to allantoins, which are ten times more soluble than uric acid and easily eliminated by the kidneys. Recently, Sanofi Research isolated a recombinant urate oxidase (SR29142) as a cDNA clone from Aspergillus flavus, expressed in the yeast strain Saccharomyces cerevisiae. Preclinical studies have documented its biological effects as a urolytic enzyme. Twenty-eight healthy male volunteers received SR29142, and a rapid decline of uric acid below measurable levels was seen within 4 h in all patients receiving a dose of more than 0.10 mg kg(-1). Currently, SR29142 is undergoing clinical studies in both Europe and the USA in patients with acute leukaemias or B-cell non-Hodgkin's lymphoma to demonstrate its efficacy and safety in this population of patients at highest risk of developing ATLS or its life-threatening sequelae.
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PMID:Advances in the management of malignancy-associated hyperuricaemia. 964 16

The effect of purine enzyme inhibition on catecholamine metabolism was investigated in guinea pigs. Catecholamine levels were measured in the nigrostriatal brain structures of male guinea pigs following treatment with allopurinol (a xanthine oxidase inhibitor; 250 mg/kg i.p.) or allantoxanimide (a uricase inhibitor; 200 mg/kg i.p.) once a day for 4 days. Tissue was analyzed from the striatum and the substantia nigra. Norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid, and uric acid were quantified with electrochemical and ultraviolet detection following separation by liquid chromatography. Allopurinol had no effect on nigrostriatal dopamine levels but decreased DOPAC levels (P<0.05) in the striatum. Allantoxanimide increased norepinephrine levels and decreased DOPAC levels in the striatum (P<0.05). Allopurinol decreased uric acid levels in the striatum and substantia nigra (P<0.05). Allantoxanimide increased uric acid levels in the striatum and the substantia nigra (P<0.05). These results indicate that alterations in purinergic enzyme activity can influence catecholamine metabolism within the nigrostriatal system of the guinea pig.
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PMID:Nigrostriatal catecholamine metabolism in guinea pigs is altered by purine enzyme inhibition. 1044 6

In this study, the hypouricemic efficacy of a novel xanthine oxidase/xanthine dehydrogenase inhibitor, TEI-6720, was compared with that of allopurinol in a hyperuricemic rat model established by feeding the animals oxonate, a uricase inhibitor. In addition, using normal rats, the changes in xanthine concentration in plasma and the concentrations and absolute quantities of uric acid, allantoin and xanthine in urine were analyzed during a 28-day period of repeated administration of TEI-6720 to determine the changes occurring during this period and the conditions required for the formation of xanthine crystals and calculi in comparison with allopurinol. TEI-6720 and allopurinol caused a significant dose-dependent decrease in plasma uric acid levels in the hyperuricemic rat model and the ED50 of TEI-6720 was lower than that of allopurinol, indicating that in terms of hypouricemic efficacy TEI-6720 is more potent than allopurinol. TEI-6720 also showed more potent activity than allopurinol in decreasing urinary uric acid and allantoin levels in normal rats. In addition, TEI-6720 and allopurinol showed similar dose-response curves for the decrease in uric acid or allantoin concentration, and the associated increase in xanthine concentration, indicating that TEI-6720 and allopurinol have similar pharmacological characteristics although the dosage required differs. The efficacy of TEI-6720 in increasing plasma and urinary xanthine levels in normal rats was approximately 10- to 30-fold greater than that of allopurinol. However, with respect to renal xanthine calculus formation, there was only about a 3-fold difference in dosage comparing TEI-6720 and allopurinol. This difference suggests that there may be another factor independent of xanthine, and dependent on the drug itself, involved in renal calculus formation caused by allopurinol. The daily excretion of purine metabolites per body weight was about 20-fold higher in rats than in humans. From these results, it is concluded that TEI-6720 has potent hypouricemic activity and that, compared to allopurinol, administration of TEI-6720 is not likely to result in a higher incidence of calculus formation.
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PMID:A comparative study on the hypouricemic activity and potency in renal xanthine calculus formation of two xanthine oxidase/xanthine dehydrogenase inhibitors: TEI-6720 and allopurinol in rats. 1074 81

The influence of hypoxanthine (HX)/xanthine oxidase (XO) on short-term [electrical field stimulation (EFS; 4 Hz) for 10 s and 3 min; bolus of exogenous NO (10(-5) M)] and long-term [EFS (4 Hz) and continuous NO-infusion for 20 min] nitrergic relaxations was investigated in circular muscle strips of the pig gastric fundus. HX (3x10(-4) M) / XO (64 mu ml(-1)) did not affect EFS for 10 s and 3 min; the short-lasting relaxation in response to a bolus of exogenous NO (10(-5) M) was changed into a biphasic relaxation with a small and short first phase followed by a larger and prolonged second phase. Cu/Zn superoxide dismutase (Cu/Zn SOD; 1000 u ml(-1)) and uricase (100 mu ml(-1)) respectively enhanced the amplitude of the first phase and diminished the amplitude of the second phase. Ascorbate (5x10(-4) M) and bilirubin (2x10(-4) M) prevented the prolonged component. Exposure to HX/XO during long-term EFS elicited a complete, stable reversal of relaxation starting after a delay. During continuous NO-infusion, HX/XO induced an immediate, complete but transient reversal. The antioxidants bilirubin, ascorbate, alpha-tocopherol, urate, glutathione and Cu/Zn SOD, the hydrogen peroxide degrading enzyme catalase, the hydroxyl radical scavengers dimethylsulphoxide and mannitol, and the cofactor flavin adenine dinucleotide did not influence the reversal induced by HX/XO during either EFS or NO-infusion. The cell-permeable manganese SOD mimetic EUK-8 modified the stable reversal during long-term EFS into a transient one. The results suggest that a nitrated uric acid derivative is responsible for the prolonged second phase in the relaxation to a bolus of exogenous NO in the presence of HX/XO. The exact underlying mechanism of the reversal induced by HX/XO during sustained relaxation remains unclear.
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PMID:Interaction of hypoxanthine/xanthine oxidase with nitrergic relaxation in the porcine gastric fundus. 1080 74

In our previous experiments on rat liver we found that 15' after intraperitoneal administration of 14C-formate the specific radioactivity of allantoin was always higher than that of uric acid. The present experiments have been carried out to interpret this unexpected result, which was only observed in liver and we studied: a) the incorporation of 14C-glycine into uric acid and allantoin; b) the effects of two competitive inhibitors of xanthine oxidase and uricase, oxonic acid and allopurinol respectively, on levels of uric acid and allantoin in liver and on their specific radioactivity after administration of labelled precursor. The results suggested: a) that under normal conditions, the formation of allantoin is so fast that it exceedes export from liver to serum, and thus the radioactivity of labelled precursors accumulates in allantoin; b) that when allopurinol or oxonic acid are administered, the rate of export exceeds that of allantoin formation and the incorporation of radioactivity into allantoin is lower; c) that not all the data, however, could be interpreted on this basis, but seems to require the existence of different pools of uric acid, which are transformed separately into allantoin.
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PMID:Purine nucleotide catabolism in rat liver: labelling of uric acid and allantoin after treatment with oxonic acid and allopurinol. 1122 97


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