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)

Data are presented which suggest that Duchenne muscular dystrophy (DMD) may have some origin in a severe deficiency of total muscle adenine nucleotides. Using double-blind techniques, this possibility was tested in 16 DMD patients by giving oral allopurinol, a synthetic inhibitor of the purine catabolic enzyme xanthine oxidase. Sublingual procaine adenylate was also briefly tested. Instances of clinical improvement quickly occurred which were statistically significant; they were accompanied by a significant increase in physical strength. These improvements have been maintained for more than 6 mo by administration of a small amount of allopurinol daily. Procaine adenylate had little effect. These results support the above view of DMD and seem to indicate that existing purines, retained and recycled after allopurinol, can sustain such improvement, and that additional adenylate is unnecessary.
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PMID:X-linked recessive (Duchenne) muscular dystrophy (DMD) and purine metabolism: effects of oral allopurinol and adenylate. 2 83

Adenosine produced from 5'-AMP has been proposed as a mediator of intrinsic renal regulation. The rates of 5'-AMP and adenosine metabolism are dependent on the activities of enzyme involved in purine metabolism. The activities of adenosine kinase (AK), adenosine deaminase (ADA), 5'-nucleotidase (5'-NT), AMP deaminase, xanthine oxidase and purine nucleoside phosphorylase were measured in cytosolic and membrane fractions from glomeruli, cortical tubules, medullary thick ascending limb of Henle (MTAL) and collecting duct prepared from rat kidney by combinations of sieving and sucrose density gradient centrifugation techniques. In the cytoplasm of glomeruli cells, the activity ratios of ADA/AK and AMP deaminase/5'-NT were 70 and 2.4, respectively. The highest activity of 5'-NT was found in membrane fractions of cortical tubules where it was equally distributed between luminal and antiluminal membranes. Membrane fractions of MTAL did not contain detectable amounts of adenosine deaminase activity. The highest activity of xanthine oxidase and purine nucleoside phosphorylase was in the cytoplasm fraction of glomeruli. These results suggest that deamination of AMP and adenosine may be favored in the cytoplasm of glomeruli cells. In contrast, in the extracellular space of glomeruli and especially in the cortical tubule, AMP can be converted preferentially to adenosine by 5'-NT.
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PMID:The distribution of enzymes involved in purine metabolism in rat kidney. 161 Aug 88

The purpose of this study was to clarify the involvement of adenine nucleotide metabolism and substrates of the xanthine-xanthine oxidase system as the source of oxygen free radicals in a rat model of restrained water immersion stress ulceration. The gastric mucosal concentrations of adenine-5'-triphosphate (ATP), adenine-5'-diphosphate (ADP), adenine-5'-monophosphate (AMP) and thiobarbituric-acid (TBA)-reactant substances were measured after 4, 8 and 12 h restrained water immersion stress. The gastric mucosal concentrations of the nucleoside adenosine, the purine bases xanthine and hypoxanthine, and the final metabolic product uric acid, were measured after 4 h of restrained water immersion stress. The concentrations of ATP diminished significantly after 4, 8 and 12 h of restrained water immersion stress. However, the observed stress-induced changes in ADP were not significant. AMP concentrations increased significantly after 4, 8 and 12 h of stress. The adenylate pool (ATP + ADP + AMP) dropped significantly from the prestress value after 4, 8 and 12 h of stress, and the concomitant energy charge (EC = ATP + 0.5 ADP/ATP + ADP + AMP) decreased significantly after 4 and 8 h of stress compared with the prestress value. Gastric mucosal concentrations of TBA-reactant substances displayed a significant increase after 4 h of stress, and remained unchanged after 8 and 12 h of stress from the level after 4 h. Four hours of restrained water immersion stress induced an increase in adenosine and uric acid concentrations and a decrease in the hypoxanthine concentration of the gastric mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in gastric mucosal content of adenosine, xanthine and hypoxanthine induced by restrained water immersion stress: antiulcer effects of tetraprenylacetone. 186 66

The purpose of this study was to better characterize renal adenine nucleotide pool responses to different forms of shock, contrast the changes to those found in other intra-abdominal organs (the liver and small intestine), and assess whether these changes are closely mimicked by those produced by renal arterial occlusion, the usual method used to study ischemic acute renal failure. Rats were subjected to hemorrhagic shock, septic shock, or cardiopulmonary shock of varying severities and durations. The liver consistently had the greatest energy depletion, followed by the kidney, and then the small intestine. However, only the kidney developed clear morphological damage (S3 brush border sloughing). Kidney adenylate pools were better preserved during septic shock and cardiopulmonary shock than during hemorrhagic shock despite comparable blood pressures. Only profound hemorrhagic shock (35-40 mm Hg for 25 minutes) decreased total adenylate pools (ATP + ADP + AMP). However, the degree of renal catabolite (nucleosides plus purine base) accumulation did not correlate with the amount of renal total adenine nucleotide depletion, partially because circulating catabolites contributed to intrarenal catabolite pools. Purine base/uric acid ratios differed among shocked organs, consistent with different degrees of xanthine oxidase activity (small intestine greater than liver greater than kidney). Renal morphological damage decreased during the immediate (0-30 minutes) postshock period, and the extent of this improvement was not altered by xanthine oxidase inhibition (oxypurinol), suggesting that the immediate postshock period is not one of serious oxidative injury. Shock, in comparison with renal arterial occlusion, caused only modest ATP loss/catabolite accumulation, very low purine base/uric acid ratios, and no immediate-reperfusion (0-30 minutes) resynthesis of the total adenylate pool. Thus, ischemia-induced renal adenylate changes may differ considerably, depending on the nature of the ischemic event.
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PMID:Adenine nucleotide changes in kidney, liver, and small intestine during different forms of ischemic injury. 198 61

1. A low protein diet prevents the development of proteinuria and glomerular damage in adriamycin experimental nephrosis without affecting renal haemodynamics. In this study the hypothesis was tested as to whether protein restriction is able to modulate the purine metabolic cycle and related enzymes such as xanthine oxidase, one of the putative effectors of adriamycin nephrotoxicity. 2. Renal activities of xanthine oxidase and purine nucleoside phosphorylase were markedly depressed in adriamycin-treated rats fed a 9% casein (low protein) diet compared with the group fed a 22% casein (normal protein) diet both 1 day after adriamycin administration and at the time of appearance of heavy proteinuria (day 15), whereas the activity of renal adenosine deaminase was unchanged. 3. The concentrations of the metabolic substrates of xanthine oxidase, i.e. hypoxanthine and xanthine, were constantly lower in renal homogenates of rats fed a low protein diet compared with those on a normal protein diet. In urine, uric acid, the product of hypoxanthine-xanthine transformation, was lower 1 day after adriamycin injection in protein-restricted rats compared with the group on a normal protein diet which showed a marked increase in its excretion. At the same time, the urinary efflux of adenosine 5'-monophosphate, which is the precursor nucleotide of the above-mentioned nucleosides and bases, was very high in rats fed a low protein diet, whereas it was absent in the group on a normal protein diet. 4. The progressive increment in proteinuria of glomerular origin (i.e. increased excretion of albumin and transferrin) typical of adriamycin-treated rats fed a normal protein diet was inhibited in the protein-restricted animals, which were normoproteinuric on day 10 and were only slightly proteinuric on day 15. 5. Like protein restriction, the pharmacological suppression of renal xanthine oxidase by dietary tungstate and the scavenging by dimethylthiourea of the putative free radical deriving from the action of xanthine oxidase, were associated with a similar (quantitative and qualitative) inhibition of glomerular proteinuria. 6. These data demonstrate that dietary protein restriction is associated with a block in purine metabolism within the kidney due to a marked reduction in the activities of two main enzymes of the cycle, i.e. purine nucleoside phosphorylase and xanthine oxidase, the latter being a putative effector of adriamycin nephrotoxicity. The partial reduction of proteinuria induced by a low protein diet is quantitatively and qualitatively comparable with the reduction induced by the specific block of renal xanthine oxidase or by the scavenging of OH.deriving from hypoxanthine and xanthine transformation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of dietary protein restriction on renal purines and purine-metabolizing enzymes in adriamycin nephrosis in rats: a mechanism for protection against acute proteinuria involving xanthine oxidase inhibition. 217 53

Effects of xanthine (2 mM) and xanthine oxidase (10 U/L) perfusion on myocardial function, lipid peroxide content, high-energy phosphates and their metabolites, and ultrastructure were examined in isolated perfused rat hearts to define the time course of myocardial injury due to exogenous supply of active oxygen species. Peak-developed force and dF/dt showed a decline within 5 min and complete contractile failure was seen at 20 min. Resting tension was higher at 10 min and reached a maximum value of 400% at 40 min. These changes in contractile parameters were reduced by superoxide dismutase (1.2 x 10(5) U/L), catalase (2 and 4 X 10(4) U/L), and mannitol (10 and 20 mM). Lipid peroxide content was significantly higher at 5 min and rose continuously with xanthine-xanthine oxidase (X-XO) perfusion. A close correlation was noted (r = 0.935) between increased lipid peroxide content and a decrease in peak-developed force. Creatine phosphate and adenosine triphosphate (ATP) showed a time-dependent decrease due to X-XO perfusion. Loss of ATP also correlated (r = 0.819) with the contractile failure. Adenosine diphosphate showed an increase at 5 min followed by a decrease at 20 and 40 min. Adenosine monophosphate, adenosine, and creatine content increased with X-XO perfusion. In a semiquantitative morphometric study, significant myocardial and vascular changes became apparent only after 10 min of X-XO perfusion. When a 5-min perfusion with X-XO was followed by a control perfusion, a recovery of developed force and normal structure was noted at 40 min. These data show that X-XO induced contractile failure involves partially reduced forms of oxygen such as superoxide, hydroxyl radicals, and hydrogen peroxide. The negative inotropic effect of a vascular supply of these active oxygen species may be related to increased lipid peroxidation as well as the loss of high-energy phosphates. Structural damage to myocytes and blood vessels and a rise in resting tension were delayed events requiring a continuous and longer exposure to radical species.
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PMID:Time course of structure, function, and metabolic changes due to an exogenous source of oxygen metabolites in rat heart. 262 93

Adenosine kinase, adenosine deaminase, hypoxanthine phosphoribosyltransferase, inosine-nucleoside phosphorylase, 5'-AMP deaminase and 5'-IMP nucleotidase were identified in cell-free extracts of duckling erythrocytes; no evidence for 5'-AMP nucleotidase and xanthine oxidase activity was found. The Km values for the duckling red cell enzymes were similar to those reported for human erythrocytes. Plasmodium lophurae extracts demonstrated similar enzyme activities except for 5'-AMP deaminase and 5'-IMP nucleotidase which were absent. It is proposed that during infection erythrocytic AMP is catabolized to IMP, inosine and hypoxanthine; the hypoxanthine is taken up by the plasmodium, utilized to form IMP, and this in turn is converted into adenine and guanine nucleotides.
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PMID:Purine metabolizing enzymes of Plasmodium lophurae and its host cell, the duckling (Anas domesticus) erythrocyte. 678 22

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

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

The current study was done to evaluate the effects of short term (60 minutes) pancreatic biliary duct obstruction (PBDO) with intraductal hypertension (IDH) stimulated by secretin (0.2 clinical unit per kilogram per hour) and caerulein (0.2 microgram per kilogram per hour) plus 30 minutes of temporary pancreatic ischemia (ISCH) produced by ligation of celiac and superior mesenteric artery on the exocrine pancreas and protective effects of a new potent protease inhibitor, ONO3307 in combination with xanthine oxidase inhibitor, allopurinol, in this multifactor related model of acute pancreatitis in rats. Twelve hours after PBDO with IDH plus ISCH, we observed hyperamylasemia (23 +/- 3 units per milliliter) (p < 0.01); moderate pancreatic histologic changes; pancreatic edema (water content--81 +/- 2 percent) (p < 0.02), as well as the impaired amylase (2,889 +/- 328 units per kilogram per hour) (p < 0.01) and cathepsin B output (7 +/- 3 units per kilogram per hour) (p < 0.01) into the pancreatic juice of rats stimulated by caerulein (control group--serum amylase levels, 6 +/- 1 units per milliliter; pancreatic water content, 74 +/- 1 percent. Furthermore, PBDO with IDH plus ISCH caused the redistribution of lysosomal enzyme from lysosomal fraction (12 kilo times gravity pellet; 40 +/- 3 percent; p < 0.01) to zymogen fraction (1.3 kilo times gravity pellet; 38 +/- 3 percent; p < 0.01) (control group--12 kilo times gravity pellet, 59 +/- 2 percent; 1.3 kilo times gravity pellet, 24 +/- 2 percent) and the impaired pancreatic adenylate energy metabolism (0.79 +/- 0.02, p < 0.02) (control group--energy charge equals 0.88 +/- 0.01). Only PBDO with IDH caused no significant changes. Although only ONO3307 or allopurinol therapy showed the partial significant protective effects against pancreatic injuries, improving serum amylase levels, the administration of ONO3307 in combination therapy with allopurinol showed almost complete protective effects against the pancreatic injuries induced by PBDO with IDH plus ISCH (serum amylase levels, 9 +/- 2 units per milliliter; pancreatic water content, 76 +/- 2 percent; amylase and cathepsin B output, 7,127 +/- 946 and 18 +/- 3 units per kilogram per hour; 1.3 kilo times gravity pellet, 28 +/- 2 percent; 12 kilo times gravity pellet, 54 +/- 2 percent, and energy charge equals 0.85 +/- 0.02).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Protective effects of therapy with a protease and xanthine oxidase inhibitor in short form pancreatic biliary obstruction and ischemia in rats. 846 Apr 15


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