Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.1.4 (xanthine dehydrogenase)
 1,236 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The excessive generation of free radicals is thought to be one of the major mechanisms leading to tissue injury in various pathological conditions, including ischemia, inflammation, and trauma. Conversion of xanthine dehydrogenase (XDH) to xanthine oxidase (XO) contributes to the formation of superoxide, an oxygen radical. We measured XDH and XO activity using a newly developed fluorometric assay in an experimental spinal cord injury model in rats. XO activity increased by more than 100% 4 h after spinal cord trauma. Total (XDH + XO) activity also increased by 96% during the same period. Allopurinol, an inhibitor of XO (100 mg/kg/day x 2 days, i.p.), completely inhibited plasma and spinal cord XO activity but did not affect posttraumatic edema determined by water content or polymorphonuclear (PMN) cell infiltration reflected by myeloperoxidase (MPO) activity in traumatized spinal cord. These results indicate that XDH conversion to XO may not be the major mechanism of oxygen radical formation in the pathogenesis of vasogenic edema or inflammatory response in this experimental spinal cord injury model in rats.
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PMID:Xanthine oxidase in experimental spinal cord injury. 164 10

Retinal oxidase (retinoic acid synthase) (EC 1.2.3.11) was purified electrophoretically, as a single protein band, from rabbit liver cytosol. The characteristic properties, enzymatic reaction mechanism, substrate specificity and kinetic parameters for retinals and molecular oxygen of the retinal oxidase were investigated. The Km values for all-trans-retinal of the retinal oxidase was the lowest than those for the other retinal derivatives. The retinal oxidase is a metalloflavoenzyme containing 2 FADs as the coenzyme, and 8 irons, 2 molybdenums, 2 disulfide bonds and 8 inorganic sulfurs. Its relative molecular mass was determined to be 270 kDa by gel filtration HPLC on a TSKgel G3000swXL column. Its minimum molecular mass was estimated to be 135 kDa by SDS-PAGE. The optical spectrum of the retinal oxidase showed absorption peaks at 275, 340 and 450 nm, and shoulders at 420 and 473 nm, in the oxidized form. The molecular extinction coefficients of the oxidase at selected wavelengths were determined. Circular dichroism spectra of the retinal oxidase were measured in the ultraviolet and visible regions. These spectra showed positive absorption in the visible region. The amino-acid composition was determined. The activity of the oxidase was not affected by any cofactors, such as NADP+, NAD+, NADPH and NADH, and it did not occur under anaerobic conditions. The oxidase was not inhibited by BOF-4272, a potent inhibitor of xanthine dehydrogenase, or rat anti-xanthine dehydrogenase IgG. Experiments on retinoic acid formation under 18O2 or H2(18)O demonstrated that the oxygen of water was incorporated into retinoic acid by the retinal oxidase, but not molecular oxygen.
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PMID:Characteristic properties of retinal oxidase (retinoic acid synthase) from rabbit hepatocytes. 830 67

We have previously shown that nitric oxide (NO) donors, such as nitrosoglutathione, inhibit endothelial cell (EC) xanthine dehydrogenase (XD)/xanthine oxidase (XO) activity. The purpose of this study was to assess whether endothelial-derived NO plays any role in the regulation of intracellular XD/XO. We exposed rat pulmonary microvascular EC to L-arginine (precursor of NO) or inhibitors of nitric oxide synthase (NOS), i.e., NG-nitro-L-arginine methyl esther (L-NAME) and NG-nitro-L-arginine, in conditions of normoxia, hypoxia, and hypoxia followed by reoxygenation. Hypoxia alone caused a 1.9- and a 6.6-fold increase in XO and a 5-fold increase in XO + XD activities after 24 and 48 h of exposure, respectively. The combination of hypoxia and L-NAME (300 microM) treatment amounted at 48 h to a 10- and 7.5-fold increase in XO and XO + XD activities, respectively, compared with normoxic untreated cells. L-NAME also prevented the decline in XD/XO activity that occurred in untreated EC after hypoxia-reoxygenation. On the other hand, treatment with L-arginine caused a dose-dependent decrease in XD/XO activity in hypoxic EC compared with cells provided with L-arginine-free medium. In separate experiments, we assessed the role of L-arginine supplementation on the in vivo regulation of lung XD/XO by exposing male adult Sprague-Dawley rats for a period of 5 days to a hypoxic hypobaric atmosphere (0.5 atm). Exposure to hypoxia produced a significant increase in lung tissue XO activity and an increase in the ratio of XO to XD. L-Arginine supplementation in the drinking water prevented the increase in lung XO and the XO-to-XD ratio in hypoxic rats and caused a significant decrease in XO and XD in rats exposed to normoxia. In conclusion, this study suggests that endogenous NO has a significant role in the regulation of XD/XO both in vitro and in vivo. By inhibiting XD/XO activity, NO may have a modulating effect in conditions of hypoxia and hypoxia-reoxygenation, where this enzyme is thought to be important.
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PMID:Regulation of intracellular xanthine oxidase by endothelial-derived nitric oxide. 894 32

In rats subjected to water immersion restraint (WIR) stress for 1, 3, and 6 h, gastric mucosal lesions developed time-dependently with an increase in lipid peroxide (LPO) levels and a decrease in nonprotein sulfhydryl levels in the gastric mucosa. The gastric mucosal xanthine oxidase (XO) activity significantly increased with the conversion of xanthine dehydrogenase (XD) to XO at 6 h of WIR (3.2-fold that of the control group without WIR). A significant increase in myeloperoxidase (MPO) activity, an index of neutrophil infiltration, occurred in the gastric mucosa at 3 and 6 h of the WIR (2.2- and 3.3-fold that of the control group without WIR, respectively). In contrast, superoxide dismutase, catalase, and glutathione peroxidase activities in the gastric mucosa did not change during the WIR period. Pretreatment with either allopurinol (AP), an inhibitor of XO, or soybean trypsin inhibitor (STI), a serine protease inhibitor, attenuated the lesion development at 6 h of WIR, but not at 3 h. In the gastric mucosa of rats pretreated with AP, enhancements of LPO formation, sulfhydryl oxidation, and XO activity found at 6 h of WIR were prevented with inhibition of XD plus XO activity, while in the gastric mucosa of rats pretreated with STI, these enhancements were prevented with inhibition of the conversion of XD to XO. In the gastric mucosa of rats pretreated with anti-polymorphonuclear leukocyte antiserum, the lesion development and enhanced LPO formation and sulfhydryl oxidation found at 3 and 6 h of WIR were prevented with a decrease in increased MPO activity. These results indicate that in the gastric mucosa of rats with WIR stress, the progression of lesions is mainly related to enhanced LPO formation and sulfhydryl oxidation which depend on an increased generation of oxygen free radicals via the xanthine-XO system and neutrophils rather than the change in the oxygen free radical-scavenging activity of antioxidant enzymes. The present results also suggest that increased gastric mucosal LPO formation and sulfhydryl oxidation found at 3 h of WIR could be mainly due to neutrophil-derived oxygen free radicals, while enhanced gastric mucosal LPO formation and sulfhydryl oxidation found at 6 h of WIR could be due to both neutrophil- and XO-derived oxygen free radicals.
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PMID:Involvement of the xanthine-xanthine oxidase system and neutrophils in the development of acute gastric mucosal lesions in rats with water immersion restraint stress. 932 61

In humans, adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency can manifest as nephrolithiasis, interstitial nephritis, and chronic renal failure. APRT catalyzes synthesis of AMP from adenine and 5-phosphoribosyl-1-pyrophosphate. In the absence of APRT, 2,8-dihydroxyadenine (DHA) is produced from adenine by xanthine dehydrogenase (XDH) and can precipitate in the renal interstitium, resulting in kidney disease. Treatment with allopurinol controls formation of DHA stones by inhibiting XDH activity. Kidney disease in APRT-deficient mice resembles that seen in humans. By age 12 wk, APRT-deficient male mice are, on average, mildly anemic and smaller than normal males. They have extensive renal interstitial damage (assessed by image analysis) and elevated blood urea nitrogen (BUN), and their creatinine clearance rates, which measure excretion of infused creatinine as an estimate of glomerular filtration rate (GFR), are about half that of wild-type males. APRT-deficient males treated with allopurinol in the drinking water had normal BUN and less extensive visible renal damage, but creatinine clearance remained low. Throughout their lifespans, homozygous null female mice manifested significantly less renal damage than homozygous null males of the same age. APRT-deficient females showed no significant impairment of GFR at age 12 wk. Consequences of APRT deficiency in male mice are more pronounced than in females, possibly due to differences in rates of adenine or DHA synthesis or to sex-determined responses of the kidneys.
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PMID:Chronic renal failure in a mouse model of human adenine phosphoribosyltransferase deficiency. 968 17

This study investigated the in vitro dose effects of ethanol (EtOH), adenosine (ADO), and urate (URA) on the basal and CRF stimulated ACTH production of pituitary tissue culture (PTC). Furthermore, the effects of low (LE = 0.5 g/kg bodyweight) and high (HE = 2.5 g/kg bodyweight) concentrations of EtOH were tested in rats on plasma ACTH and corticosterone concentration (PCC), with or without the following ADO metabolic pathway inhibitors: 6-mercaptopurine (6MP) (salvage pathway) and purpurogallin (PPG) (xanthine dehydrogenase). EtOH at 0-50 mM does not increase the in vitro basal or CRF (10-7 M) stimulated ACTH secretion in PTC; in fact doses up to 20 mM tended to be inhibitory. ADO significantly increased only basal ACTH secretion whereas URA increased both basal and CRF-stimulated ACTH secretion. Pretreatment with PPG or 6MP + PPG significantly increased both in vivo ACTH and PCC over control values in rats. HE versus LE significantly increased ACTH and PCC in the control (H2O) and 6MP pretreated groups whereas in the PPG pretreated animals, only ACTH was increased significantly by HE. However, combined pretreatment with 6MP + PPG prevented the effect of HE on ACTH and PCC. The current experiment suggests that purine metabolism is involved in ethanol's effect on the hypothalamic-pituitary-adrenal axis.
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PMID:Ethanol's effect on rat pituitary adrenal axis is prevented by purine metabolic pathway inhibitors. 993 6

Hypertension may be associated with an increase in oxidative stress as a possible mechanism for the increased vascular tone and organ injury. Previously, we reported an increased production of reactive oxygen species and endothelial cell death in the microcirculation of hypertensive rats. We hypothesize that xanthine oxidase (XO) may be a potential source of oxidants induced by glucocorticoid-induced hypertension. Male Wistar rats were administered dexamethasone (0.5 mg/kg/day) for 5 days to induce hypertension. After general anesthesia, cremaster muscle was collected for analysis of XO and xanthine dehydrogenase (XDH) activities. The mean blood pressure and XO levels in cremaster muscle were significantly increased in the dexamethasone-treated rats compared with controls. There was a strong age-dependent rise in total XO + XDH activity in all groups. To inhibit XO, we administered allopurinol (ALLO, 0.4 mg/mL) in the drinking water to a subset of control and dexamethasone-treated rats during a 5-day treatment. The ALLO significantly reduced the mean arterial blood pressure in the dexamethasone-treated rats. Although in the cremaster muscle the total XO + XDH levels were not completely reduced with ALLO, the XO levels of the dexamethasone-treated + ALLO rats were reduced to levels of the control + ALLO group. These results suggest that dexamethasone induces an elevated level of XO activity in the cremaster muscle. The enhanced XO activity can be attenuated by chronic allopurinol treatment.
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PMID:Xanthine oxidase activity in the dexamethasone-induced hypertensive rat. 1282 72

Molybdenum is widely distributed in biology and is usually found as a mononuclear metal center in the active sites of many enzymes catalyzing oxygen atom transfer. The molybdenum hydroxylases are distinct from other biological systems catalyzing hydroxylation reactions in that the oxygen atom incorporated into the product is derived from water rather than molecular oxygen. Here, we present the crystal structure of the key intermediate in the hydroxylation reaction of xanthine oxidoreductase with a slow substrate, in which the carbon-oxygen bond of the product is formed, yet the product remains complexed to the molybdenum. This intermediate displays a stable broad charge-transfer band at approximately 640 nm. The crystal structure of the complex indicates that the catalytically labile Mo-OH oxygen has formed a bond with a carbon atom of the substrate. In addition, the MoS group of the oxidized enzyme has become protonated to afford Mo-SH on reduction of the molybdenum center. In contrast to previous assignments, we find this last ligand at an equatorial position in the square-pyramidal metal coordination sphere, not the apical position. A water molecule usually seen in the active site of the enzyme is absent in the present structure, which probably accounts for the stability of this intermediate toward ligand displacement by hydroxide.
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PMID:The crystal structure of xanthine oxidoreductase during catalysis: implications for reaction mechanism and enzyme inhibition. 1514 1

Ermiao wan, which is composed of phellodendri cortex and atractylodis rhizome, is described as eliminating heat, excreting dampness and anti-edema prescription in traditional Chinese medical literatures including Danxi's Experiences in Medicine and State Pharmacopoeia of People's Republic of China. So it is being used clinically in the treatment of gout and hyperuricemia in China. In the present study, the water extracts of Ermiao wan and phellodendri cortex at 840 and 480 mg/kg/day orally for 7 days were demonstrated to possess in vivo potent hypouricemic effects both in hyperuricemic mice pretreated with oxonate and in normal mice, respectively. In the hyperuricemic animals, the effect of Ermiao wan was equal to that of the reference drug allopurinol (at 10 mg/kg/day orally for 7 days), but in the normal mice, the former was weaker than latter. In addition, both Ermiao wan and phellodendri cortex were found to have in vivo relatively inhibitory effects on mouse liver xanthine dehydrogenase (XDH) and xanthine oxidase (XO) activities at the same dose described above. These inhibitory effects were weaker than that observed for allopurinol. Atractylodis rhizome at 340 mg/kg/day orally for 7 days did not show any effects on the above experiments. These results suggested that atractylodis rhizomes assisted and enhanced the effect of phellodendri cortex on reduction of serum uric acid level in hyperuricemic mice, and hypouricemic effects of Ermiao wan and phellodendri cortex may be achieved by other mechanism partly instead of the XDH and XO inhibition.
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PMID:A Chinese herbal medicine Ermiao wan reduces serum uric acid level and inhibits liver xanthine dehydrogenase and xanthine oxidase in mice. 1523 72

A genetic approach was cited for species detection of the ameba genus Naegleria using allozyme electrophoresis to characterize the trophozoite stage of three strains of Naegleria fowleri isolated from patients with primary amebic meningoencephalitis, five thermophilic (45 degrees C) Naegleria spp isolated from natural water sources in the Taling Chan district, and a reference control strain, Naegleria fowleri CDC VO 3081. Isoenzymes of ameba whole-cell extracts were analyzed by vertical polyacrylamide slab gel electrophoresis to determine whether there was any correlation between different strains of the ameba. The results showed that five out of fifteen enzymes; aldehyde oxidase (ALDOX), aldolase (ALD), a-glycerophosphate dehydrogenase (a-GPDH), xanthine dehydrogenase (XDH), and glutamate oxaloacetate transaminase (GOT), were undetectable in the pathogenic strains, while the other enzymes; esterase (EST), fumerase (FUM), glucose-6-phosphate dehydrogenase (G-6-PDH), glucose phosphate isomerase (GPI), isocitate dehydrogenase (IDH), lactate dehydrogenase (LDH), leucine aminopeptidase (LAP), malic enzyme (ME), glucose phosphomutase (GPM), and malate dehydrogenase (MDH), were detected. Naegleria fowleri strains were biochemically the most homogeneous. They showed intraspecific isoenzyme variation that allowed them to be grouped. In contrast, the allozyme patterns (EST 1-7, IDH) of Naegleria spp isolated from the environment showed interspecific isoenzyme variations from the pathogenic Naegleria strain. In conclusion, this study recognized the zymograms of the Naegleria fowleri strains were heterogenically different from the thermophilic 45 degrees C Naegleria spp isolated from the environment.
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PMID:Zymogram patterns of Naegleria spp isolated from natural water sources in Taling Chan district, Bangkok. 1569 Nov 24


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