Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to evaluate the possible involvement of xanthine and xanthine oxidase in reperfusion injury in a low-flow, reflow model of liver perfusion. Livers were perfused at flow rates around 25% of normal for 90 min and then at normal flow rates (4 ml/g/min) for 30 min. When flow was restored to normal, malondialdehyde and lactic dehydrogenase (LDH) were released into the effluent perfusate. Malondialdehyde production rapidly reached values of 300 nmol/g/hr whereas LDH increased from basal levels of 100 to 600 U/l upon reperfusion. Trypan blue was taken up exclusively in cells in pericentral regions of the liver lobule under these conditions. Xanthine and hypoxanthine in the effluent perfusate increased steadily during the low-flow period reaching values around 5 and 10 microM, respectively, and decreased rapidly after the flow was restored to normal. Perfusion with nitrogen-saturated buffer for 3 min before restoration of normal flow rates or infusion of the radical scavenger catechin (400 microM) reduced cell damage by about 50%. Infusion of allopurinol (2-6 mM), an inhibitor of xanthine oxidase, prevented reperfusion injury in a dose-dependent manner. Taken together, these data indicate that a reperfusion injury occurs in liver upon reintroduction of oxygen which is initiated by oxidation of xanthine and hypoxanthine via xanthine oxidase and ultimately leads to production of lipid peroxides. Surprisingly, infusion of xanthine (4 mM), substrate for xanthine oxidase, reduced hepatocellular injury on reperfusion. LDH release was decreased from values around 700 to less than 200 U/l and trypan blue uptake in pericentral region was prevented totally by xanthine.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Role of purines and xanthine oxidase in reperfusion injury in perfused rat liver. 254 32

The "desulfo-inhibited" Mo(V) center of bovine milk xanthine oxidase has been investigated by electron-nuclear double resonance spectroscopy. Comparison of spectral data obtained from samples prepared with [1H4]ethylene glycol and with [2H4]ethylene glycol allowed assignment of proton resonance lines due to the methylene protons of the coordinated ethylene glycol (AH = 3.6 MHz). Deuterium resonance lines were observed with the deuterated sample (AD = 0.4 MHz). No spectral evidence was obtained for any weakly coupled nitrogen nuclei to the Mo center under a variety of conditions. Dissolution of the sample in D2O had little effect on the resonance lines centered about the proton Zeeman frequency, which shows they are not due to exchangeable protons and suggests the Mo center does not have contact with bulk solvent. A deuterium delta m = +/- 2 "forbidden" transition is observed at high radio-frequency power levels, which suggests either an exchangeable proton on a Mo ligand or a coordinated solvent. Weakly coupled, nonexchangeable proton lines are observed about the free proton frequency, which exhibit properties characteristic of alpha-protons. A number of arguments are presented to support the proposal that these protons originate from the C(1') and C(2') positions on the side chain of the molybdopterin cofactor.
 ...
PMID:Electron-nuclear double resonance spectroscopy of the desulfo-inhibited molybdenum(V) center in bovine milk xanthine oxidase. 255 65

Activities of alanine and aspartate transaminases, glutamine synthetase, adenylate deaminase, glutamate and xanthine dehydrogenases and lactate dehydrogenase were measured in leg and breast muscles of developing chicks from day 10 in ovo to day 5 of free life, and compared with measurements for adult hens. Xanthine dehydrogenase activity was low in both muscles with adult levels attained on day 15 in ovo. Glutamine synthetase for chicks was maintained higher during development than for adults in both muscles. Minor differences were observed between both muscles in all enzymes tested up to day 18. With low embryonic values and important rises before hatching, the differences were initiated in the posthatching period. Important differences were observed between adult levels of activity. Leg muscle revealed higher enzyme values except for lactate dehydrogenase and indistinguishable levels for adenylate deaminase and xanthine dehydrogenase in both muscles. Alanine, instead of glutamine, is postulated as the main nitrogen transport between muscle and liver in the domestic fowl.
 ...
PMID:Patterns of amino acid enzyme in domestic fowl breast and leg muscle during development. 286 43

Xanthine dehydrogenase (XDH) is the initial enzyme in the purine catabolic pathway of N. crassa. Secondary nitrogen sources such as purines are metabolized when preferred sources of reduced nitrogen (ammonium or glutamine) are unavailable. XDH synthesis is regulated by glutamine repression and uric acid induction. The nit-2 locus is believed to encode a trans-acting positive regulator essential for the expression of genes encoding enzymes involved in secondary pathways of nitrogen acquisition, such as XDH and nitrate reductase. However, immunoblot analyses and enzyme assays reveal that XDH protein is synthesized and XDH activity is expressed in nit-2 mutants. Nevertheless, XDH responds to nitrogen metabolite repression. The generality that nit-2 is an obligate control element in nitrogen metabolite repression is questioned. Additionally, mutants defective in XDH activity, namely, xdh-1 and the molybdenum cofactor mutants nit-1, -7, -8 and -9, are observed to grow on xanthine but not hypoxanthine.
 ...
PMID:Xanthine dehydrogenase expression in Neurospora crassa does not require a functional nit-2 regulatory gene. 296 94

The reduction of the hypoxic cell toxin 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) was investigated using pulse radiolysis, radiation chemical reduction, and xanthine oxidase. Evidence was found that the one-electron reduction product of the parent compound is an oxidizing radical that caused single- and double-strand breaks in plasmid DNA and that produced a malondialdehyde-like thiobarbituric acid adduct from 2-deoxy-D-ribose. Possible forms of the reactive radical, either carbon- or nitrogen-centered, are suggested. The "natural" lifetime of the radical was sufficiently long that it could diffuse over significant distances within hypoxic cells and thus inflict oxidative damage on cellular targets. The radical reacted with O2 at a rate comparable to those of the nitroimidazoles misonidazole and metronidazole. Thus, the selectivity for hypoxic cells is probably due to the elimination of "futile" reduction when the cellular oxygen concentration is sufficiently low.
 ...
PMID:Molecular mechanisms for the hypoxia-dependent activation of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233). 312 84

Oxygen radicals derived from xanthine oxidase (XO) are important mediators of the cellular injury associated with reperfusion of ischemic intestine, stomach, liver, kidney, and pancreas. XO exists in nonischemic tissue predominantly as xanthine dehydrogenase (XDH) and converts to oxygen radical-producing XO with ischemia. Grinding intestine under liquid nitrogen and placing the powder in phosphate buffer (pH 7.0) containing thiol reductants and protease inhibitors adequately preserved total XDH + XO activity and the percentage in the oxidase form (%XO) for 24 h. Total activity in nonischemic intestine ranged from 374 nmol.min-1.g-1 in duodenum to 138 nmol.min-1.g-1 in ileum, while XO activity was approximately 19% of total activity throughout the entire small intestine. The rate of XDH conversion to XO during normothermic ischemia varied only slightly throughout the intestine, increasing 13% per hour to 34, 46, and 61% XO after 1, 2, and 3 h of ischemia, respectively. Our results contrast with previous reports where XDH conversion to XO occurred within 60 s ischemia but are consistent with physiological and morphological evidence of ischemic injury and provide further support for involvement of XO in intestinal injury associated with ischemia.
 ...
PMID:Conversion of xanthine dehydrogenase to oxidase in ischemic rat intestine: a reevaluation. 316 36

Porfiromycin was reductively metabolized by NADPH cytochrome P-450 reductase and xanthine oxidase under anaerobic conditions. The production of metabolites varied with the pH and the contents of the reaction buffer. In Tris buffer, two major metabolites were produced at pH 7.5 and above, whereas one major metabolite was produced at pH 6.5. The three major metabolites were separated and isolated by HPLC. Identification by californium-252 plasma desorption mass spectrometry showed that the two major metabolites from pH 7.5 were (trans) and (cis)-forms of 7-amino-1-hydroxyl-2-methylaminomitosene and the major metabolite from pH 6.5 was 7-amino-2-methylaminomitosene. All three major metabolites showed substitutions at the C-1 position. DNA was alkylated readily by enzyme-activated porfiromycin. Digestion of porfiromycin-alkylated DNA by DNase, snake venom phosphodiesterase, and alkaline phosphatase resulted in an insoluble nuclease-resistant fraction and a soluble fraction. The nuclease-resistant fraction reflected a high content of cross-linked adducts. Upon HPLC analysis, the solubilized fraction contained two monofunctionally linked porfiromycin adducts and a possibly cross-linked dinucleotide. The major adduct was isolated by HPLC and identified by NMR, as N2-(2'-deoxyguanosyl)-7-amino-2-methylaminomitosene. The N2 position of deoxyguanosine appeared as the major monofunctional alkylating site for DNA alkylation by porfiromycin. Thus, mitomycin C and porfiromycin (which differs from mitomycin C only by the addition of a methyl group to the aziridine nitrogen) share the same enzymatic activating mechanism that leads to the formation of the same types of metabolites and the same specificity of DNA alkylation.
 ...
PMID:Metabolites and DNA adduct formation from flavoenzyme-activated porfiromycin. 341 25

Within the scope of our molecular modeling studies on xanthine oxidase (XOD) inhibition by purine analogs we were interested to build up a three-dimensional model of the molybdenum active site. Spectroscopic data indicated that a Mo (VI)atom which is coordinated to sulfur, oxygen and/or nitrogen is clearly involved in substrate binding. In the present study, those data and X-ray crystallography data were used to reconstruct molybdenum-organic complexes from models proposed in the literature. The computer graphic-assisted modeling and evaluation of the model complexes show that the description of the molybdenum center needs further refinement.
 ...
PMID:Computer graphic study on models of the molybdenum cofactor of xanthine oxidase. 350 88

Nitrated polycyclic aromatic compounds, 1-nitropyrene (1-NP) and 1,6-dinitropyrene (1,6-diNP), are environmental mutagens and carcinogens. Nitroreductases purified from an anaerobic bacterium, Bacteroides fragilis, catalyzed the metabolic activation of these compounds to produce DNA- and tRNA-bound adducts in vitro. Formation of the adducts was inhibited by p-chloromercuribenzoic acid, which is an inhibitor of nitroreductases from B. fragilis. The enzyme and coenzyme (NADPH) were essential for the adduct formation. These results suggest that nitroreduction is a necessary step in the metabolic activation of nitropyrenes. 1-NP bound specifically to poly(G) and poly(dG), and 1,6-diNP bound to poly(G), poly(dG), and poly(X). The other purine polynucleotides were weak acceptors. However, the reactive products of nitropyrenes formed by nitroreductases could not bind to pyrimidine polynucleotides. Enzymatic hydrolysis of 1-NP-bound DNA and subsequent analysis by high-performance liquid chromatography showed one major and two minor adducts in the hydrolysate. The peak of the major adduct corresponded to that of N-(deoxyguanosin-8-y1)-1-aminopyrene, which is the same as an adduct formed by xanthine oxidase, a mammalian nitroreductase. Nitroreductase activity in the various organs and intestinal contents of Sprague-Dawley rats was assayed in the presence of NADPH or NADH under nitrogen gas. Nitroreductase activity was widely distributed in the organs of the rats; in particular, that of the liver and of the small intestine was relatively high, but that of the respiratory organs such as lung and alveolar macrophages was very low. Intestinal contents had high nitroreductase activity, which was proportional to the number of bacteria, especially anaerobic bacteria, in the intestine. These results suggest that the nitroreductase activity of the normal bacterial flora is very high in rats and that the intestinal bacteria play a major role in the metabolism of nitropyrenes in vivo.
 ...
PMID:Metabolic activation of 1-nitropyrene and 1,6-dinitropyrene by nitroreductases from Bacteroides fragilis and distribution of nitroreductase activity in rats. 379 18

3-Deazaguanine (dezaguanine, USAN; CI-908) is a new antipurine antimetabolite which is entering Phase I studies in the USA. This compound differs from guanine only in the substitution of a carbon for the 3-nitrogen of guanine. Dezaguanine has an unusual spectrum of activity against experimental rodent tumors; its activity against transplantable rodent leukemias is only modest, but it has significant activity against transplantable rodent solid tumors, particularly mammary adenocarcinomas. Mammary adenocarcinoma models against which this compound is active include slow and fast-growing tumors, hormone sensitive and hormone insensitive tumors, and the subrenal capsule implanted human breast cancer xenograft, MX-1. Dezaguanine must be converted to its nucleotides to be active. Dezaguanine nucleotides inhibit synthesis of guanine nucleotides, and can be incorporated into nucleic acids in place of guanine nucleotides; incorporation into DNA may be particularly important in the cytotoxicity of this compound. Addition of certain purines or purine nucleosides can prevent dezaguanine cytotoxicity in vitro. Preclinical studies suggest that dezaguanine does not undergo deamination to 3-deazaxanthine, and is not metabolized by xanthine oxidase. Therefore, this compound may not be subject to metabolic inactivation in vivo, and active metabolites may have a prolonged half-life. This concept is supported by the prolonged half-life of radiolabelled dezaguanine in rats. Finally, dezaguanine can cross the blood-brain barrier. In summary, the novel biochemical and experimental antitumor properties of dezaguanine indicate that this compound could have better activity against some human solid tumors than currently used purine antimetabolites.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Dezaguanine mesylate: a new antipurine antimetabolite. 406 18


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>