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)

The activities of five enzymes involved in purine salvage and catabolism--hypoxanthine phosphoribosyl transferase (HPRT), adenine phosphoribosyl transferase (APRT), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and guanase--were measured in mouse embryo extracts, from the one-cell to the blastocyst stage. Xanthine oxidase activity was not detected. The analyses were performed using high performance liquid chromatography and the enzymes showed different patterns of activity during development. Activities of HPRT, APRT and PNP were low before morula formation, and then increased until the blastocyst stage. ADA and guanase showed high activities after fertilization; guanase activity decreased sharply after the two-cell stage and ADA activity decreased sharply after the morula stage. Blastocyst formation was accompanied by a further decline in activity of both enzymes. The methods used may be suitable for measuring these enzymes in single human embryos, or in biopsies derived from them.
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PMID:Enzymes of purine salvage and catabolism in the mouse preimplantation embryo measured by high performance liquid chromatography. 806 75

Activities of adenosine deaminase (ADA), 5'nucleotidase (5NT), xanthine oxidase (XO), superoxide dismutase (SOD), and catalase (CAT) enzymes were measured in cancerous and cancer-free adjacent bladder tissues from 36 patients with bladder cancer and in control bladder tissues from 9 noncancer patients. Increased ADA and decreased XO, SOD, and CAT activities were found in cancerous bladder tissues compared with those of cancer-free adjacent tissues and of control bladder tissues. Differences were also found between enzyme activities in the bladder of different disease stages and grades. In the cancerous tissues, only positive intracorrelations were found, but in the cancer-free adjacent tissues and control tissues, both positive and negative correlations were established between enzyme activities. Results suggested that purine metabolism and salvage pathway activity of purine nucleotides were accelerated in the cancerous human bladder tissues via increased ADA and decreased XO activities, probably together with changes in some other related enzyme activities and, free radical metabolising-enzyme activities were depressed in cancerous bladder tissues, which indicated exposure of cancerous tissues to more radicalic stress.
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PMID:Adenosine deaminase, 5'nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in cancerous and noncancerous human bladder tissues. 807 Jun 87

Previous studies showed that in cultured chick ciliary ganglion neurons and CNS glia, adenosine can be synthesized by hydrolysis of 5'-AMP and that the accumulation of the adenosine degradative products inosine and hypoxanthine was significantly greater in glial than in neuronal cultures. Furthermore, previous immunochemical and histochemical studies in brain showed that adenosine deaminase and nucleoside phosphorylase are localized in endothelial and glial cells but are absent in neurons; however, adenosine deaminase may be found in a few neurons in discrete brain regions. These results suggested that adenosine degradative pathways may be more active in glia. Thus, we have determined if there is a differential distribution of adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase enzyme fluxes in glia, comparing primary cultures of central and ciliary ganglion neurons and glial cells from chick embryos. Hypoxanthine-guanine phosphoribosyltransferase and production of adenosine by S-adenosylhomocysteine hydrolase activity were also examined. Our results show that there is a distinct profile of purine metabolizing enzymes for glia and neurons in culture. Both cell types have an S-adenosylhomocysteine hydrolase, but it was more active in neurons than in glia. In contrast, in glia the enzymatic activities of xanthine oxidase (443 +/- 61 pmol/min/10(7) cells), nucleoside phosphorylase (187 +/- 8 pmol/min/10(7) cells), and adenosine deaminase (233 +/- 32 pmol/min/10(7) cells) were more active at least 100, 20, and five times, respectively, than in ciliary ganglion neurons and 100, 100, and nine times, respectively, than in central neurons.
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PMID:Differential distribution of purine metabolizing enzymes between glia and neurons. 811 1

We determined activities of adenosine deaminase (ADA), 5' nucleotidase (5NT), xanthine oxidase (XO), superoxide dismutase (Cu-Zn SOD), and catalase (CAT) enzymes in 15 human laryngeal tissues with well-differentiated squamous cell carcinomas, in 15 corresponding tumor-free adjacent tissues and in 7 normal laryngeal tissues. We found lower ADA and 5NT and higher XO, Cu-Zn SOD, and CAT activities in cancerous tissues than those in corresponding noncancerous ones. In the correlation analysis, we established one positive intercorrelation, which was between ADA activities of tumor tissues and noncancerous adjacent tissues. We also found some significant intracorrelations between enzyme activities of the tissues, all of which were positive in cancerous ones.
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PMID:Adenosine deaminase, 5' nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in cancerous and noncancerous human laryngeal tissues. 813 95

Phagocytic cells respond to a variety of membrane stimulants by producing reactive oxygen intermediates (ROI), i.e. O2-, H2O2 and OH.metabolites. Plasma membrane activation is associated with superoxide generating NADPH oxidase, thereby causing the production of these toxic species. Stimulation of phagocytic cells also results in activation of purine catabolism, which directs the metabolic flux through xanthine oxidase to produce the superoxide anion. We previously observed that BL/LL macrophages (M phi) exhibited a premature inability to undergo tuftsin stimulated phagocytosis and microbicidal activity. The present study was undertaken to measure ROI levels in the absence and presence of 'tuftsin' pulsing as a function of in vitro culture age and also correlated these levels with adenosine deaminase (ADA) activity. The latter is known to be a contributor of O2- generation and is also involved in the maturation of the monocyte/macrophage system. The behaviour of normal and tuberculoid monocytes/macrophages were more or less the same, either in the presence or absence of tuftsin, i.e. they showed a progressive increase in ROI production until day 3, then tapered off in older cultures by day 7. In contrast, after day 1, the lepromatous macrophages were unable to undergo tuftsin mediated stimulation for the production of ROI and ADA activity. These findings indicate a defective M phi function in lepromatous patients towards tuftsin pulsing, thereby supporting our earlier observations. Thus BL/LL M phi behaved as if they were aged after 1 day of in vitro culture, which may account for an inability to handle Mycobacterium leprae for efficient killing.
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PMID:Modulation of peripheral blood derived monocytes/macrophages from leprosy patients using 'tuftsin' for production of reactive oxygen intermediates. 823

Research leading to the new anti-herpesvirus compounds discussed here has come from three approaches. The first approach was directed towards improving the bioavailability of acyclovir by examining the potential of a variety of prodrugs, leading to the new compound valaciclovir hydrochloride. The second approach was to examine a large number of 5-substituted pyrimidines for activity against those viruses which were not as potently inhibited by acyclovir as are herpes simplex viruses, i.e., varicella zoster virus (VZV) and human cytomegalovirus (HCMV). This research led to the new chemical entity 882C for VZV. A third approach has been to examine drug combinations with acyclovir. This research led to the compound 348U, an inhibitor of herpes simplex virus ribonucleotide reductase which acts synergistically in combination with acyclovir. This manuscript will focus on the first two approaches leading to new compounds valaciclovir hydrochloride and 882C since Dr. Safrin details such background for 348U/acyclovir. Attempts to improve the bioavailability of acyclovir began a decade ago. Early prodrugs were compounds with alterations in the 6-substituent of the purine ring of acyclovir. The 6-amino congener required the cellular enzyme adenosine deaminase for conversion to acyclovir and the 6-deoxycongener was dependent on cellular xanthine oxidase for conversion. Neither of these prodrugs had a chronic toxicity profile in laboratory animals as good as acyclovir. Efforts were directed towards simpler esters and 18 amino acid esters were made. The pharmacokinetic profile of each prodrug was determined in rats by measuring the recovery of acyclovir in urine after oral dosing.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Review of research leading to new anti-herpesvirus agents in clinical development: valaciclovir hydrochloride (256U, the L-valyl ester of acyclovir) and 882C, a specific agent for varicella zoster virus. 824 81

When human umbilical vein endothelial cells were prelabeled with [14C]-adenine and then exposed to xanthine oxidase (40 mU/ml) and hypoxanthine (100 microM) for 4 h, cellular adenine nucleotides were depleted (18 +/- 3% of total radioactivity vs. 61 +/- 10% in controls), nucleotides appeared in the culture medium (8 +/- 3% vs. 4 +/- 3%) together with the catabolic products inosine, hypoxanthine, and uric acid (74 +/- 4% vs. 35 +/- 11%). In the presence of H2O2 (100 microM) for 30 min, cellular nucleotides were depleted (46 +/- 25%) and catabolic products appeared in the medium (40 +/- 26%), but radioactive nucleotides in the medium were unaltered. In the presence of an inhibitor of ecto-5'-nucleotidase [alpha, beta-methylene-adenosine 5'-diphosphate (ADP), 0.5 mM], exposure to xanthine oxidase and hypoxanthine resulted in the appearance of three times more nucleotides in the culture medium than in the absence of the inhibitor, but there was no change in medium nucleotides after H2O2 exposure. In the presence of an inhibitor of adenosine deaminase (2-deoxycoformycin, 2 microM), both exposures caused an accumulation of adenosine in the medium, calculated to represent a minimum of 25% of nucleotide catabolism. We conclude that exposure to both a superoxide-generating system (hypoxanthine plus xanthine oxidase) and H2O2 induce catabolism of adenine nucleotides, which mainly takes place through adenosine 5'-monophosphate (AMP) deaminase. However, superoxide but not H2O2 also causes membrane damage and leakage of nucleotides into the medium.
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PMID:Mechanisms of adenine nucleotide depletion from endothelial cells exposed to reactive oxygen metabolites. 838 Nov 5

A new kinetic method for the determination of serum adenosine deaminase (EC 3.5.4.4) is described, with adenosine as the substrate and nucleoside phosphorylase and xanthine oxidase as the reaction enzymes. Inosine is produced, which is converted to hypoxanthine. The hypoxanthine is oxidized to xanthine, which is further oxidized to uric acid. In these two reactions, blue 2,6-dichlorophenolindophenol is reduced to a colorless compound and the decrease in color is measured spectrophotometrically at 606 nm. The assay was automated by using a Cobas Mira analyzer. The automated assay had a CV of < 7%, and the calibration curve was linear from 10 to 120 U/L. The assay correlates well with an established method, based on detection of liberated NH3 with Berthelot's reaction. The reference interval (mean +/- 2 SD) was 14-34 U/L (mean 24 U/L, n = 84). The enzymatic method described is easily automated and seems to be suitable for the routine determination of adenosine deaminase in serum.
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PMID:Kinetic determination of serum adenosine deaminase. 840 5

Exogenous adenosine triphosphate (ATP) added to brush-border membrane vesicles was rapidly degraded mainly to inosine according to the high ecto-nucleotidase activities in these vesicles. In the absence of phosphate, inosine was slowly transformed into hypoxanthine, and xanthine oxidase and dehydrogenase activities were not detected. The presence of ecto-adenosine deaminase and ecto-adenosine monophosphate (AMP) nucleotidase was shown. The ecto-adenosine deaminase was inhibited by deoxycoformycin and was also detected in rat renal brush-border membrane vesicles. Using orthovanadate, levamisole, and alpha, beta-methylene adenosine diphosphate as possible inhibitors, alkaline phosphatase was shown to be the main agent responsible for ecto-AMP nucleotidase activity. In pig renal basolateral membrane vesicles and in whole cell extracts from pig renal cortex, ecto-AMP nucleotidase was the limiting factor in ATP degradation. Comparing the ATP catabolism in the whole cell cortical extract with the catabolism in the same sample precleared of membranes, it was shown that ectonucleotidase activity is mainly bound to the membranous components. It is also shown that the whole cell extract of pig renal cortex has hypoxanthine phosphoribosyl transferase activity, and it seems probable that the rapid and specific formation of luminal inosine and its transport into the cell in competition with adenosine may start the purine salvage pathway through the synthesis of IMP from hypoxanthine.
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PMID:Adenine nucleotides and adenosine metabolism in pig kidney proximal tubule membranes. 840 44

In the presence of its substrates hypoxanthine and xanthine, xanthine oxidase generates oxygen free radicals that cause postischemic injury. Recently, it has been demonstrated that the burst of xanthine oxidase-mediated free radical generation in the reperfused heart is triggered by a large increase in substrate formation, which occurs secondary to the degradation of adenine nucleotides during ischemia. It is not known, however, whether blocking this substrate formation is sufficient to prevent radical generation and functional injury. Therefore, studies were performed in isolated rat hearts in which xanthine oxidase substrate formation was blocked with the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), and measurements of contractile function and free radical generation were performed. Chromatographic measurements of the intracellular adenine nucleotide pool showed that preischemic administration of EHNA blocked postischemic hypoxanthine, xanthine, and inosine formation. Electron paramagnetic resonance spin trapping measurements of free radical generation showed that inhibition of adenosine deaminase with EHNA blocked free radical generation and that it also increased the recovery of contractile function by more than 2-fold. Exogenous infusion of hypoxanthine and xanthine totally reversed the protective effects of EHNA. These results demonstrate that blockade of xanthine oxidase substrate formation by adenosine deaminase inhibition can prevent free radical generation and contractile dysfunction in the postischemic heart.
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PMID:Adenosine deaminase inhibition prevents free radical-mediated injury in the postischemic heart. 862 67


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