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 effects of acidic and intestinal proteolytic environments on bovine milk xanthine oxidase (XO) activity were determined in order to evaluate the extent to which this enzyme was absorbed in biologically active form. The inhibition of XO by folic acid and the relative affinities of XO for the oxidation of palmitaldehyde, stearaldehyde, and xanthine were compared. The effects of acid and gastric juice on XO activity were measured by incubating purified enzyme, and non-purified enzyme (milk), in buffers ranging in pH from 2 to 9. Fresh gastric juice was also incubated with milk. Increasing amounts of the enzyme were inactivated as the pH of the incubation mixture was reduced below pH 6.5. Below pH 3.5, the enzyme was completely inactivated. Gastric juice, pH juice incubated with milk. Milk XO activity was reduced 36% when mild was incubated with an equal volume of gastric juice. Homogenized milk had 59% less XO activity compared with raw molk. Fresh raw milk XO, homogenized milk XO, and purified XO were equally susceptible to inactivation by acid or gastric juice. After incubation of milk with gastric juice, or gastric juice followed by pancreatin, XO activity was associated with a macromolecule of 300,000 daltons molecular weight and subunits containg activity were not found. It was estimated that 0.00008% of the XO in the intestine was absorbed. Both folic acid and allopurinol inhibited XO activity in vitro. Allopurinol was 3.5 times more potent an inhibitor than folic acid. A large excess of dietary folic acid did not reduce rat liver or intestinal XO activity in vivo. XO had a much greater affinity for xanthine than for palmitaldehyde or stearaldehyde substrates. It was estimated that of 100 mg of XO in fresh raw milk, 41 mg remained after homogenization, 27 mg entered the intestine and only 20 ng were absorbed as intact enzyme.
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PMID:Digestion and absorption of bovine milk xanthine oxidase and its role as an aldehyde oxidase. 1 Mar 60

Biochemical effects of treatment with a xanthine oxidase inhibitor (allopurinol) were investigated in an experimental hemorrhagic shock procedure. Allopurinol pretreatment abolished the increase in plasma uric acid which occurs in untreated dogs during hemorrhagic hypotension and resulted in a much lesser increase in plasma allantoin. The pancreatic, liver and duodenal adenosine triphosphate (ATP) and total adenine nucleotides of untreated dogs were severely reduced, while those of allopurinol-pretreated dogs were essentially normal 2 h following reinfusion. Pretreatment with allopurinol resulted in a significantly lesser release of the lysosomal enzymes, acid phosphatase and beta-glucuronidase, following reinfusion. When treatment was delayed until after reinfusion, an infusion of hypoxanthine + allpurinol restored normal ATP concentrations. The role of adenine nucleotide breakdown in irreversible shock is discussed.
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PMID:Effect of a xanthine oxidase inhibitor on adenine nucleotide degradation in hemorrhagic shock. 71 Apr 57

NADH-FMN oxidoreductase has been proposed as an enzyme involved in the release of iron from ferritin. The effects of riboflavin and/or iron deficiencies and of dietary allopurinol on the activities of this enzyme and on the iron contents of liver, kidney and duodenum were investigated. Allopurinol, a xanthine oxidase inhibitor, did not affect organ enzyme activities nor iron contents. Riboflavin-deficient rats and iron-deficient rats both had significantly lower organ enzyme activities and iron contrnts than controls. Organ enzyme activities and iron contents of rats fed a diet deficient in both iron and riboflavin were significantly lower than those of controls. After dietary iron and/or riboflavin repletion, organ enzyme activities and iron contents increased. Rats fed an irons-overload diet had enzyme activities similar to that of controls, but organ iron contents were significantly increased over those of controls. Effects of riboflavin and/or deficiencies in rats on NADH-FMN oxidoreductase activities and iron contents of liver, kidney and duodenum appeared to be reversible by riboflavin and/or iron supplementation. The data support the view that NADH-FMN oxidoreductase may be a controlling enxyme in iron release from ferritin.
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PMID:NADH-FMN oxidoreductase activity and iron content of organs from riboflavin and iron-deficient rats. 85 41

The xanthine oxidase inhibitor, 4-hydroxypyrazolo(3,4-d) pyrimidine (HPP), Allopurinol, caused augmentation of myocardial uptake of [3H] hypoxanthine, which was eventually completely incorporated into ATP. The decrease of [32P] orthophosphate incorporation into ATP induced by isoproterenol was restored by HPP administration.
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PMID:Effect of xanthine oxidase inhibitor on myocardial ischemia. 103 53

The production of reactive oxygen species in the ovary is rapidly inducible, but the nature of the generator is unknown. One possibility is xanthine oxidase (XO), an enzyme that produces superoxide in the presence of hypoxanthine (or xanthine) and oxygen. The objective of the present studies was to measure levels of XO in follicular and luteal tissue to determine whether XO may be a source of reactive oxygen species in the rat ovary. Ovarian levels of XO were about one-fifth of that seen in the liver and adrenal, and XO levels were about one-third of xanthine dehydrogenase (XDH). Preovulatory ovarian levels of XO activity were unchanged after induction of ovulation with gonadotropin and in follicles incubated with gonadotropin. Luteal XO activity was not changed during natural or prostaglandin F2 alpha (PGF2 alpha)-induced luteolysis. Allopurinol, an inhibitor of XO, did not inhibit ovulation or PGF2 alpha-induced luteal regression. Finally, neither catalase and superoxide dismutase nor oxypurinol altered luteal cell function in the presence of hypoxanthine. Thus, while XO is present in the ovary, it does not appear that it is a major source of reactive oxygen species in this organ.
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PMID:Xanthine oxidase and dehydrogenase activities in rat ovarian tissues. 131 8

Oxygen free radicals have been demonstrated to be important mediators in postischemic reperfusion injury. In this study, I determined the superoxide and the hydrogen peroxide generation from human umbilical endothelial cells on reoxygenation following anoxic incubation (1% O2, 5% CO2, 94% N2). The superoxide generation, detected by the reduction of cytochrome, c, was at its maximum 3 minutes after reoxygenation in any anoxic interval. The hydrogen peroxide production, detected by the fluorometric analysis, was observed later than that of superoxide. Treatment of EC with superoxide dismutase and allopurinol attenuated the superoxide production, and catalase attenuated the hydrogen peroxide. Cell injury was assessed by both fura-2 release assay and trypan blue dye exclusion methods. Although cell injury was less than 20% in anoxic condition, it was remarkably increased after reoxygenation. However this cell injury was not completely prevented in the presence of free radical scavengers. Allopurinol was more effective than superoxide dismutase or catalase. In conclusion, EC are the major source of free radicals in postischemic reperfusion which are originated mainly from xanthine-xanthine oxidase system and these radicals may also contribute, at least in part, to the EC injury.
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PMID:[Measurement of free radical generation from endothelial cells and observation of cell injury exposed to anoxia-reoxygenation]. 131 95

Using the isolated perfused rat liver, we examined the effect of stimulation of mitochondrial respiration by 2,4-dinitrophenol (2,4-DNP) and adrenaline on reactive oxygen species (ROS) production, liver damage and lipid peroxidation. ROS production was monitored by luminol- and lucigenin-enhanced chemiluminescence and oxygen uptake was measured simultaneously. Liver damage and lipid peroxidation were evaluated by measuring hepatic lactate dehydrogenase (LDH) and thiobarbituric acid reacting substances (TBARS) release. Tissue ROS level decreased and oxygen uptake increased soon after 2,4-DNP infusion. On termination of 2,4-DNP infusion, there was a sharp increase in lucigenin-enhanced chemiluminescence, which declined slowly, but luminol-enhanced chemiluminescence did not change prominently. Hepatic LDH and TBARS release increased gradually during 2,4-DNP infusion and were manifested by termination of the infusion. Allopurinol did not affect ROS production and TBARS release, but delayed increases in LDH release after termination of 2,4-DNP infusion. Adrenaline, which stimulates mitochondrial respiration without uncoupling caused similar but smaller ROS changes observed in 2,4-DNP. LDH and TBARS release were not affected significantly by adrenaline infusion. These results indicate that uncoupling of oxidative phosphorylation decreases ROS production and restoration of oxidative phosphorylation enhances ROS production and liver damage. Xanthine oxidase is unlikely to contribute to enhanced ROS production after termination of 2,4-DNP but has some protective effect during uncoupling.
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PMID:Comparison of the effect of a mitochondrial uncoupler, 2,4-dinitrophenol and adrenaline on oxygen radical production in the isolated perfused rat liver. 132 18

1. 2,6-Dinitrotoluene (2,6-DNT) metabolism by human liver and male Fischer F344 rat liver subcellular fractions under aerobic (100% oxygen) and anaerobic (100% nitrogen) incubation conditions was examined. Under aerobic conditions the major 2,6-DNT metabolite formed by hepatic microsomes was 2,6-dinitrobenzyl alcohol (2,6-DNBalc); under anaerobic conditions 2-amino-6-nitrotoluene (2Am6NT) was the major metabolite. 2. Rates of 2,6-DNBalc formation by human and rat liver microsomes under aerobic conditions were 247 and 132 pmol/min per mg protein, respectively. Rates of 2Am6NT formation by human and rat liver microsomes under anaerobic conditions were 292 and 285 pmol/min per mg protein, respectively. Anaerobic reduction of 2,6-DNT to 2Am6NT by rat and human liver microsomes was inhibited by carbon monoxide and metyrapone, which indicates that microsomal metabolism of 2,6-DNT to 2Am6NT is mediated by cytochrome P-450. 3. Liver cytosolic fractions also metabolized 2,6-DNT to 2Am6NT under anaerobic conditions. Formation of 2Am6NT by human and rat liver cytosols was supported by hypoxanthine, NADPH and NADH. Allopurinol inhibited the hypoxanthine-supported anaerobic metabolism of 2,6-DNT by rat, but not human, liver cytosol. Dicumarol inhibited the NADPH-supported anaerobic metabolism of 2,6-DNT by human, but not rat, liver cytosol. These results indicate that xanthine oxidase contributes to the hypoxanthine-supported anaerobic metabolism of 2,6-DNT by human liver cytosol.
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PMID:Metabolism of 2,6-dinitro[3-3H]toluene by human and rat liver microsomal and cytosolic fractions. 141 78

To investigate the pathophysiology of warm ischemia (WI) of the liver, the changes in hemodynamics and energy metabolism were studied during and after 60-min complete WI induced by total hepatic vascular exclusion (HVE) in the canine model. Hepatic arterial blood flow after WI was maintained at 76% of the pre-ischemic level, while portal blood flow was only 27% of the pre-ischemic level associated with increased portal vein pressure, which was twice the pre-ischemic level, resulting in a decrease of total hepatic blood flow to 46% of the pre-ischemic level. Concentration of tissue lipid peroxide increased after WI. Arterial blood ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state, could not recover to the pre-ischemic level after termination of WI. However, when 100 mg/kg of allopurinol (xanthine oxidase inhibitor) was administered intravenously 10 min prior to initiating WI, AKBR was restored to the pre-ischemic level at 30 min after WI in spite of the fact that allopurinol administration to one group produced no remarkable changes in the hepatic hemodynamics compared with the group without allopurinol treatment. Concentration of adenine nucleotides was significantly higher for the treated group at the end of and after WI than for the group without allopurinol treatment and was maintained at a higher level even after WI. Lipid peroxide production was suppressed. Electron microscopic examination revealed that allopurinol treatment could not prevent mitochondrial swelling. It is suggested that WI causes injury primarily to the portal sinusoidal circulation, resulting in portal congestion concomitant with high portal pressure after the release of WI. Allopurinol could prevent the deterioration of mitochondrial ATP metabolism, and was able to inhibit lipid peroxide production, resulting in the rapid recovery of mitochondrial redox state in spite of the fact that it produced no amelioration of hepatic hemodynamics and morphological alterations.
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PMID:Preserved mitochondrial function by allopurinol despite deteriorated hemodynamics in warm ischemia-damaged canine liver. 148 Aug 16

We propose new hypotheses for the mechanisms of streptozotocin (STZ) and alloxan inducing experimental diabetes in animals. STZ is transported into pancreatic beta cells through glucose transporter in the cell membranes and attacks mitochondria. Mitochondrial ATP generation is inhibited and the resulting high concentration of intracellular ADP causes its degradation providing hypoxanthine, a substrate of xanthine oxidase (XOD) whose activity is intrinsically very high in beta cells. Then, XOD-catalyzing reaction is proceeded as proved by increased formation of uric acid and O2- radicals are produced, but beta cells are inefficient to scavenge these radicals because of their extremely low activity of superoxide dismutase. On the other hand, STZ directly activates XOD and enhances O2- generation. Consequently, pancreatic beta cells are dually suffered from O2- radicals or probably hydroxyl radicals derived from the former when exposed to STZ. Allopurinol, an inhibitor of XOD, can protect animals from the diabetogenic effect of STZ. In pancreatic beta cells, alloxan anion radicals are generated from alloxan probably mediated by the action of microsomal cytochrome P-450 system. These radicals have long half-life and directly damage DNA in vitro. The widely accepted hypothesis that the cause of alloxan-induced diabetes is attributable to O2- radicals formed from alloxan is excluded, because alloxan itself shows a very potent scavenging effect to O2- radicals. Therefore alloxan anion radicals seem to be directly related to the incidence of diabetes by alloxan.
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PMID:[New hypotheses for the mechanisms of streptozotocin and alloxan inducing diabetes mellitus]. 148 45


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