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 synthesis of uric acid from purine bases, nucleosides and nucleotides has been measured in reaction mixtures containing rat liver supernatant and each one of the following compounds at 1 mM concentration (except xanthine, 0.5 mM and guanosine and guanine, 0.1 mM). The rates of the reaction, expressed as nanomoles of uric acid synthesized g-1 of wet liver min-1 were: ATP, 10; ADP, 37; AMP, 62; adenosine, 108; adenine 6; adenylosuccinate, 9; IMP 32; inosine, 112; hypoxanthine, 50; GTP, 19; GDP, 19; GMP, 27; guanosine, 34; guanine, 72; XMP, 10; xanthosine, 24; xanthine, 144. These figures divided by 55 correspond to nanomoles of uric acid synthesized min-1 per mg-1 of protein. The rate of synthesis of uric acid obtained with each one of those compounds at 0.1 and 0.05 mM concentrations was also determined. ATP (1 mM) strongly inhibited uric acid synthesis from 0.05 mM AMP (91 per cent) and from 0.05 mM ADP (88 per cent), but not from adenosine. CTP or UTP (1 mM) also inhibited (by more than 90 per cent) the synthesis of uric acid from 0.05 mM AMP. Xanthine oxidase was inhibited by concentrations of hypoxanthine higher than 0.012 mM. The results favour the view that the level of uric acid in plasma may be an index of the energetic state of the organism. Allopurinol, besides inhibiting uric acid synthesis, reduced the rate of degradation of AMP. The ability of crude extracts to catabolize purine nucleotides to uric acid is an important factor to be considered when some enzymes related to purine nucleotide metabolism, particularly CTP synthase, are measured in crude liver extracts.
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PMID:Uric acid synthesis by rat liver supernatants from purine bases, nucleosides and nucleotides. Effect of allopurinol. 783 12

1. The possible mechanisms of action of the inhibitory effect of gomisin C on the respiratory burst of rat neutrophils in vitro was investigated. 2. The peptide formyl-Met-Leu-Phe (FMLP) induced superoxide anion (O2-) formation and O2 consumption, which was inhibited by gomisin C in a concentration-dependent manner (IC50 21.5 +/- 4.2 micrograms ml-1 for O2- formation). Gomisin C also suppressed O2- formation and consumption at low concentrations of phorbol myristate acetate (PMA) with an IC50 value of 26.9 +/- 2.1 micrograms ml-1 for O2- formation. However, gomisin C did not affect the responses induced by a high concentration of PMA. 3. Gomisin C had no effect on O2- generation and uric acid formation in the xanthine-xanthine oxidase system, and failed to alter O2- generation during dihydroxyfumaric acid (DHF) autoxidation, indicating that it does not scavenge superoxide. 4. Like trifluoperazine (TFP), gomisin C attenuated the activity of PMA-activated neutrophil particulate NADPH oxidase in a concentration-dependent manner. 5. Gomisin C reduced the elevations of cytosolic free Ca2+ in neutrophils stimulated by FMLP in the presence or absence of EDTA. Cyclopiazonic acid (CPA) induced the release of Ca2+ from intracellular stores and this was also reduced by gomisin C. However, the Ca2+ influx pathway activated by CPA was not affected by gomisin C. 6. The cellular cyclic AMP level was markedly increased by forskolin, but not by gomisin C. Moreover, the inositol phosphate levels in FMLP-activated neutrophils were not affected by gomisin C. 7. These results show that the inhibitory action of gomisin C on the respiratory burst is not mediated by changes in cellular cyclic AMP or in inositol phosphates, or by scavenging O2- released from neutrophils, but may be mediated partly by the suppression of NADPH oxidase and partly by the decrease of cytosolic Ca2+ released from an agonist-sensitive intracellular store.
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PMID:Inhibition by gomisin C (a lignan from Schizandra chinensis) of the respiratory burst of rat neutrophils. 785 90

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

The perfused rat hindlimb preparation was used with a blood cell-free perfusate to investigate alterations in the purine nucleotide metabolism, flow rate, perfusion pressure, and venous excretion in response to ischemia and ischemia followed by reperfusion in skeletal muscle. The development of a physical hindrance during postischemic reperfusion, indicated by an increase in reperfusion pressure and a decrease in flow rate, coincided with a 90% decrease in phosphocreatine and a 50-70% reduction in total adenine nucleotide pool. The reflow impairment could not be explained by blood cell plugging of the capillaries. Washout of several metabolites was demonstrated during reperfusion. Hypoxanthine accumulated intracellularly during ischemia, and a substantial amount of uric acid was excreted into the venous effluent during reperfusion. The experimental data were fitted into a computer simulation model of the purine pathways. The model indicated that AMP deaminase was the predominant enzymatic pathway for the AMP degradation. It was demonstrated that ATP preferably accumulated as inosine-5'-monophosphate during ischemia and that xanthine oxidase was undetectable in skeletal muscle tissue homogenates. However, vascular endothelial cell xanthine oxidase activity responsible for a free radical-induced reperfusion injury could not be excluded.
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PMID:Purine metabolic pathways in rat hindlimb perfusion model during ischemia and reperfusion. 823 94

The effect of 5'-nucleotidase inhibitor (AMP-C) and xanthine oxidase inhibitor (Allopurinol: ALLO) on myocardial functional recovery and the restoration of myocardial high energy phosphates after 15 min of normothermic global ischemic insult, was studied in the isolated isovolemic Langendorff rat heart model. Fifty nine rats were divided into 4 groups: Group I; saline, Group II; AMP-C plus ALLO, Group III; AMP-C, Group IV; ALLO. Intermittent infusion of drugs was delivered in 3 ml of solution at 5 min intervals during ischemia. Percent recovery of left ventricular systolic function was as follows: Group I; 74.2 +/- 3.6%, Group II; 87.7 +/- 1.7%, Group III; 83.5 +/- 3.1%, Group IV; 86.4 +/- 2.6%. Improved recovery was statistically significant only in Group II (p < 0.05 vs Group I). Suppression of reactive hyperemia was seen with reperfusion in the groups which had been treated with AMP-C (i.e., Groups II and III). Myocardial adenine nucleotides and purines were measured in 6 hearts in each group using high performance liquid chromatography. Myocardial ATP levels was 0.89 +/- 0.16 nmol/mg left ventricular wet weight in Group I, 1.37 +/- 0.12 in Group II (p < 0.05 vs Group I), 1.42 +/- 0.17 in Group III (p < 0.05) and 1.17 +/- 0.15 in Group IV. This study demonstrates that intermittent infusion of AMP-C plus ALLO during global myocardial ischemia results in improved myocardial functional recovery and improved preservation of high energy phosphates.
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PMID:Evaluation of the effectiveness of 5'-nucleotidase inhibitor and allopurinol in myocardial ischemia. 835 99

Endothelial cells have ectonucleotidases that rapidly catabolize extracellular nucleotides. Our aim was to study whether the metabolism of extracellular nucleotides and adenosine are influenced by exposure of endothelial cells to reactive oxygen metabolites at concentrations relevant to human pathology. Human umbilical vein endothelial cells were incubated with hypoxanthine (100 microM) and xanthine oxidase (80 mU/ml), to generate superoxide, or with hydrogen peroxide (100 microM). The cells were then washed, and the metabolism of radioactive substrates was followed. After exposure to hypoxanthine-xanthine oxidase the half time of disappearance of [14C]ATP (5 microM) was prolonged from 9.9 +/- 5 to 28.3 +/- 15.6 min and that of [14C]AMP from 9.5 +/- 2.5 to 25.0 +/- 9.9 min. The conversion of extra- into intracellular nucleotides via adenosine was also decreased (mean for [14C]ATP 0.25 vs. 0.90 and for [14C]AMP, 0.075 vs. 0.75 nmol/10(6) cells in 30 min compared with parallel controls, respectively). Hydrogen peroxide or trypsin had no significant effect on the metabolism of extracellular adenine nucleotides and neither did a short (up to 15 min) exposure to the superoxide-generating system. The conversion of [14C]adenosine into intracellular nucleotides and hypoxanthine was not influenced by either hypoxanthine-xanthine oxidase or by hydrogen peroxide. We conclude that superoxide radicals inhibit the catabolism of extracellular adenine nucleotides by the ectonucleotidases of endothelial cells and may thus modify the pathophysiology of ischemia-reperfusion injury.
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PMID:Metabolism of extracellular adenine nucleotides by human endothelial cells exposed to reactive oxygen metabolites. 844 61

Cortical levels of nucleotides and their degradation products from 42 transplanted human kidneys have been studied. Biopsies were performed during renal harvesting just before cooling, at the end of cold storage, and following reinstallment of renal blood circulation. ATP levels fell, and AMP and degradation products (inosine monophosphate [IMP], inosine, adenosine, and hypoxanthine) increased during cold storage and returned to near-normal values 30 min after recirculation. The major degradation product found was hypoxanthine, indicating very poor xanthine oxidase activity in human kidneys. The sum of adenine nucleotides (ATP+ADP+AMP) did not significantly decrease after cold storage, but adenylate energy charge (ATP+1/2ADP/ATP+ADP+AMP) was reduced to half, being recovered in implanted kidneys. The sum of adenine nucleotides was significantly reduced after implantation. The rate of acute tubular necrosis was higher in kidneys preserved for more than 30 hr. Kidneys with acute tubular necrosis had significantly lower levels of the total pool of adenine nucleotides at reperfusion, but there was no correlation between incidence of acute tubular necrosis and ATP or other metabolite levels in the kidneys before or during cold preservation. The success of human kidney transplantation does not seem to depend only on the pool of residual nucleotides at the end of cold storage but on other factors that determine the ability of the cell to recover a normal energy state after reperfusion.
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PMID:Assessment of purine metabolism in human renal transplantation. 847 44

Hemorrhage rapidly increases plasma xanthine oxidase levels as well as the expression of proinflammatory and immunoregulatory cytokines in the lungs. To determine the role of circulating xanthine oxidase (XO), as well as other plasma factors, in affecting pulmonary cytokine expression, we conducted studies in which plasma from hemorrhaged mice was transferred into unhemorrhaged recipient mice. Administration of posthemorrhage plasma to recipient mice increased the levels of mRNA for interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta 1 (TGF-beta 1) in lung mononuclear cells. No enhancement of mRNA levels for these cytokines was found in the lungs of mice given allopurinol-treated posthemorrhage plasma or fed a tungsten-enriched, XO-depleting diet prior to transfer of posthemorrhage plasma. Among the nuclear transcriptional regulatory factors examined, only the cyclic AMP response-element binding protein (CREB) was activated in nuclear extracts from lung mononuclear cells of mice that were given posthemorrhage plasma. No activation of nuclear factor-kappa B (NF-kappa B), nuclear factor interleukin 6 (NF-IL6), activating protein-1 (AP-1), or serum protein-1 (SP-1) was found. These results suggest that the mechanism for hemorrhage-induced increases in pulmonary cytokine expression is by activation of the enhancer CREB through a tissue XO-dependent pathway initiated by plasma-borne mediators.
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PMID:Plasma from hemorrhaged mice activates CREB and increases cytokine expression in lung mononuclear cells through a xanthine oxidase-dependent mechanism. 863 Feb 71

Puromycin aminonucleoside (PAN) toxicity was totally inhibited in the rat in vivo and in cultured glomerular epithelial cells (GECs) in vitro using the adenosine deaminase (ADA) inhibitor, 2'-deoxycoformycin (DCF). DCF completely inhibited ADA activity in glomeruli and protected against the development of PAN nephrosis; the 24-h urinary protein excretion of treated rats compared with controls (PAN rats) 9 days after PAN injection was 16 +/- 2 mg and 524 +/- 55 mg, respectively (p < .01). Morphological examination also demonstrated that the glomerular epithelial cells were protected against PAN-induced damage. Furthermore, when DCF was added to the first passage of GECs simultaneously with PAN, the adenosine triphosphate contents of remnant GECs on culture substrata increased in a dose-dependent manner, and PA toxicity was completely inhibited by 10(-4) M DCF. The order of ADA activity in glomeruli from various species was as follows: rat > monkey > guinea pig > dog > rabbit > mouse. High activity of ADA in the glomerulus was limited to species in which PAN induced nephrosis. Additionally, DCF increased glomerular cyclic AMP contents, resulting from enhanced adenosine accumulation in the pericellular space. These results indicate that the pathogenesis of PAN toxicity is closely related to adenosine metabolism and that ADA plays a key role in this model. Furthermore, we speculate that DCF contributes to the inhibition of reactive oxygen metabolites by decreasing the substrate of xanthine oxidase and/or increasing pericellular adenosine accumulation.
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PMID:An adenosine deaminase inhibitor prevents puromycin aminonucleoside nephrotoxicity. 901 23

Xanthine dehydrogenase (XDH) and xanthine oxidase (XO) are enzymes involved in the metabolism of purines in various organisms. XO produces superoxide radicals, suggesting that is responsible for tissue ischemia-reperfusion injury. To test this notion further studies were performed on rat kidneys and the time course of changes in purine nucleotides, oxypurines and XDH and XO activity was determined. At 24 hours after reperfusion subsequent to 30-minute ischemia, serum creatinine increased to 0.83 +/- 0.74 mg/dl from 0.28 +/- 0.06 mg/dl (the level prior to ischemia, the control). Renal ATP and ADP contents were reduced after ischemia lasting for 30 minutes and restored 10 minutes after reperfusion following 30 minutes of ischemia. The renal AMP content increased after 30 minutes of ischemia and recovered within 10 minutes after reperfusion. The total adenine nucleotide (TAN) content was reduced gradually during ischemia-reperfusion in the rat kidney. Although the energy charge was reduced following 30 minutes of ischemia, it was restored to the control level 10 minutes following reperfusion. Hypoxanthine (HX) and xanthine (X), which had accumulated at 30 minutes after ischemia, were reduced to the control levels 10 minutes after reperfusion. There were no significant changes in the pre-ischemia values of total XDH and XO activities or XDH/XO ratio during the period nor at various time intervals (up to 24 hours) during reperfusion. It was shown that HX and X accumulate without significant conversion of XDH to XO during ischemia. Therefore the putative role of XO in ischemia-reperfusion injury seems to more complex than initially predicted.
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PMID:[The role of xanthine dehydrogenase (xanthine oxidase) in ischemia-reperfusion injury in rat kidney]. 901 77


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