Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chromatophores prepared from Chromatium exhibit a light-dependent O2 uptake in the presence of reduced 2,6-dichlorophenolindophenol, the maximum rate observed being 10.8 micronmol (mg of Bchl)-1 h-1 (air-saturated condition). As it was found that the uptake of O2 was markedly inhibited by superoxide dismutase, it is suggested that molecular oxygen is subject to light-dependent monovalent reduction, resulting in the formation of the superoxide anion radical (O2-). By coupling baker's yeast transketolase with illuminated chromatophore preparations, it was demonstrated that [U-14C]-fructose 6-phosphate (6-P) is oxidatively split to produce glycolate, and that the reaction was markedly inhibited by superoxide dismutase and less strongly by catalase. A coupled system containing yeast transketolase and xanthine plus xanthine oxidase showed a similar oxidative formation of glycolate from [U-14C] fructose 6-P. It is thus suggested that photogenerated O2- serves as an oxidant in the transketolase-catalyzed formation of glycolate from the alpha, beta-dihydroxyethyl (C2) thiamine pyrophosphate complex, whereas H2O2 is not an efficient oxidant. The rate of glycolate formation in vitro utilizing O2- does not account for the in vivo rate of glycolate photosynthesis in Chromatium cells exposed to an O2 atmosphere (10 micronmol (mg of Bchl)-1 h-1). However, the enhancement of glycolate formation by the autoxidizable electron acceptor methyl viologen in Chromatium cells in O2, as well as the strong suppression by 1,2-dihydroxybenzene-3,5-disulfonic acid (Tiron), an O2- scavenger, suggest that O2- is involved in the light-dependent formation of glycolate in vivo.
...
PMID:Enzymic formation of glycolate in Chromatium. Role of superoxide radical in a transketolase-type mechanism. 19 57

A quantitative structure-activity relationship for the reaction of xanthine oxidase with a homologous series of alpha, beta-unsaturated aldehydes, which are known to be products of lipid peroxidation, was investigated. Aldehydes in the series 2-butenal through 2-nonenal and 4-hydroxy-2-nonenal, displayed differential reactivity toward xanthine oxidase as measured by production of the superoxide radical anion. Kinetic parameters for the rate of superoxide production and substrate affinity were determined via the superoxide dismutase-sensitive reduction of cytochrome c. Trends in kinetic parameters as a function of carbon number for the series of trans-2-enals was consistent with a dependence on substrate hydrophobicity. Log kw', a hydrophobicity constant widely employed as a model for the octanol/water partition coefficient, was determined by reversed phase liquid chromatography for the alpha, beta-unsaturated aldehydes in this study. Linear relationships for the correlation of substrate binding (pKm) and efficiency of superoxide production (log kcat/Km) with substrate hydrophobicity (log kw') were found. The mode of inhibition of xanthine oxidation by 2-butenal is shown to be noncompetitive, suggesting distinct binding sites for purine and aldehydic substrates. It is suggested that the reaction of xanthine oxidase with unsaturated aldehydes could be an important route of amplification of oxidative damage in cells.
...
PMID:The reaction of xanthine oxidase with aldehydic products of lipid peroxidation. 166 61

Adenosine and adenine nucleotides shorten the action potential duration of atrial myocytes and activate a specific acetylcholine and adenosine receptor-operated potassium outward current referred to as IKACh,Ado. The objective of this study was to determine whether adenine nucleotides shorten the action potential duration and increase IKACh,Ado in guinea pig atrial myocytes by directly activating adenosine receptors. The potency and efficacy of AMP and adenosine in increasing IKACh,Ado and shortening atrial action potential duration were similar; the EC50 values for AMP and adenosine were 3.4 +/- 0.8 and 3.1 +/- 0.4 microM, respectively. Likewise, the maximum increases in IKACh,Ado caused by AMP and adenosine were similar (122 +/- 11% versus 123 +/- 9%). In comparison, ATP and the stable analogue of AMP, adenosine monophosphorothioate (AMPS), were significantly less potent and efficacious than adenosine and AMP, and adenosine receptor antagonist 8-(p-sulfophenyl)theophylline and abolished in the presence of adenosine deaminase and alpha, beta-methylene-ADP (APCP, an inhibitor of AMP degradation). Binding of the A1-adenosine antagonist [3H]8-cyclopentyl-1,3-dipropylxanthine (DPCPX) to guinea pig atrial membranes treated with adenosine deaminase and APCP was reduced up to 60% by 100 microM concentrations of AMP, AMPS, and adenosine. Inosine inhibited binding by 43 +/- 3% at 100 microM, whereas hypoxanthine and xanthine had little (5-10% inhibition) and uric acid had no effect. Only 3% of AMP and 35% of AMPS were recovered intact after a 90-minute incubation at 21 degrees C with preparations of guinea pig atrial membranes. Percent displacement of [3H]DPCPX binding to atrial membranes by 100 microM AMP was significantly less in the presence of nucleoside phosphorylase and xanthine oxidase (to degrade inosine, hypoxanthine, and xanthine to uric acid) than in their absence (12.4 +/- 3.1% versus 49.7 +/- 1.5%). The results suggest that the observed electrophysiological actions of adenine nucleotides in cardiomyocytes are mediated by adenosine and are consistent with activation of A1-adenosine receptors.
...
PMID:Electrophysiological and receptor binding studies to assess activation of the cardiac adenosine receptor by adenine nucleotides. 200 6

Acetylcholine and ATP are costored and coreleased during synaptic activity at the electric organ of Torpedo. It has been suggested that released ATP is converted to adenosine at the synaptic cleft, and in turn this nucleoside would depress the evoked release of acetylcholine. In the present communication we have used a chemiluminescent reaction that let us to monitor continuously the presence of adenosine in this preparation. The chemiluminescent reaction is based on the conversion of adenosine into uric acid and H2O2 by adenosine deaminase, nucleoside phosphorylase, and xanthine oxidase enzymes. The hydrogen peroxide has been detected by peroxidase-luminol mixture. The reaction has a sensitivity on the picomol range and discerned between Adenosine, AMP, ADP, and ATP. We have developed this technique in the hope of understanding whether adenosine is released during synaptic activity or it comes from the released ATP. We have studied the release or formation of adenosine in fragments of the electric organ and in isolated cholinergic nerve terminals obtained from it. In both conditions we have followed the effect of potassium stimulation upon the detection of adenosine. Potassium stimulation increased the extracellular adenosine either in slices or the synaptosomal fraction of Torpedo electric organ. The presence of alpha, beta-methylene ADP, an inhibitor of 5'-nucleotidase, inhibits the detection of adenosine, suggesting that extracellular adenosine is a consequence of ectocellular dephosphorylation of released ATP.
...
PMID:The release of adenosine at the electric organ of Torpedo. A study using a continuous chemiluminescent method. 232 27

Crude tissue or tumor extracts either do not contain sufficient inosine 5'-monophosphate dehydrogenase (IMPD) activity to be measured spectrophotometrically, or interfering enzyme activities prevent the use of a more sensitive radiochemical assay. A modified assay system which incorporates alpha, beta-methylene adenosine 5'-diphosphate, an inhibitor of 5'-nucleotidase; allopurinol, an inhibitor of xanthine oxidase; and ethylenediaminetetraacetate, an inhibitor of alkaline phosphatase, has been developed. [14C]Xanthine monophosphate produced during the assay was separated from [14C]hypoxanthine monophosphate by thin-layer chromatography on flexible diethylaminoethyl-cellulose sheets. Xanthine monophosphate formation was linear for at least 40 min and was inhibited by greater than 95% in the presence of mycophenolic acid, a specific IMPD inhibitor. Partial purified IMPD from murine EMT6 tumors was used to compare assay rates obtained with the radiochemical and spectrophotometric assays under identical conditions. The reaction rate of the radiochemical assay was 0.92 +/- 0.07 (S.E.) of the rate of xanthine monophosphate formation as determined spectrophotometrically at 290 nm, indicating that both assays are measuring product formation with an equal degree of accuracy. The improved radiochemical assay was used to determine IMPD specific activity in supernatants from EMT6 tumors and several normal mouse tissues. The observed activities (nmol/min/mg protein) were: EMT6 tumor, 0.303; spleen, 0.029; brain, 0.022; kidney, 0.015; lung, 0.009; liver, 0.008; and heart and skeletal muscle, less than 0.004.
...
PMID:Sensitive radiochemical assay for inosine 5'-monophosphate dehydrogenase and determination of activity in murine tumor and tissue extracts. 613 40

To gain insight into the gene regulation and signal transduction effects of active oxygen in tumour promotion and progression, we studied the effect of active oxygen generated extracellularly by xanthine/xanthine oxidase (X/XO) in promotion-insensitive (P-), promotion-sensitive (P+) and transformed (Tx) mouse epidermal JB6 cells. Active oxygen inhibited growth, particularly of P- cells and increased poly ADPR transferase activity and PKC activity more significantly in P- cells. No phenotypic differences in the distribution pattern of PKC isotypes alpha, beta and gamma were seen in JB6 cells. PKC alpha was expressed abundantly, whereas beta and gamma were not detected. Basal levels of the antioxidant enzymes catalase and CuZn. Superoxide dismutase were higher in P+ and Tx cells. X/XO resulted in an initial decrease in the activity of these enzymes, followed by recovery or transient induction in Tx and P+ cells. X/XO induced c-myc and c-fos expression in JB6 cells, with c-fos induction being more pronounced in P- cells, whereas a biphasic increase in c-jun was seen in P+ cells. These early genes may play a role in proliferation whereas post-translational poly ADP-ribosylation and, perhaps, phosphorylation suggest a genetic-epigenetic mechanism in oxidant tumour promotion and progression.
...
PMID:The effect of active oxygen generated by xanthine/xanthine oxidase on genes and signal transduction in mouse epidermal JB6 cells. 760 57

Caffeic acid has been reported to have activity on xanthine oxidase inhibition which is related to several diseases, e.g. gout, hepatitis and tumors. Based on this study, the alpha, beta-unsaturated COOH moiety in the molecule of caffeic acid plays a very important role on the xanthine oxidase inhibition because hydrocaffeic acid was inactive and the activities of coniferyl aldehyde and coniferyl alcohol were reduced as compared with ferulic acid. Moreover, chlorogenic acid showed a weaker activity than caffeic acid. On the other hand, the phenolic OH group present in the molecule of caffeic acid makes an important contribution to the activity, e.g. transcinnamic acid in which the absence of the phenolic OH group in the structure reduced its activity as compared with caffeic acid. Ferulic acid, isoferulic acid and 3,4-dimethoxy cinnamic acid also had reduced activity due to the methoxy groups replacing the phenolic OH group in the structures. However, m-coumaric acid displayed the strongest activity (IC50 = 63.31 microM) and induced uncompetitive inhibition with respect to the substrate xanthine (Ki = 21.568 microM). Caffeic acid (IC50 = 74.6 microM) showed the second strongest activity, followed by p-coumaric acid (IC50 = 111.09 microM).
...
PMID:Structure-activity relationship of caffeic acid analogues on xanthine oxidase inhibition. 764 46

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.
...
PMID:Mechanisms of adenine nucleotide depletion from endothelial cells exposed to reactive oxygen metabolites. 838 Nov 5

Exogenous adenosine triphosphate (ATP) added to brush-border membrane vesicles was rapidly degraded mainly to inosine according to the high ecto-nucleotidase activities in these vesicles. In the absence of phosphate, inosine was slowly transformed into hypoxanthine, and xanthine oxidase and dehydrogenase activities were not detected. The presence of ecto-adenosine deaminase and ecto-adenosine monophosphate (AMP) nucleotidase was shown. The ecto-adenosine deaminase was inhibited by deoxycoformycin and was also detected in rat renal brush-border membrane vesicles. Using orthovanadate, levamisole, and alpha, beta-methylene adenosine diphosphate as possible inhibitors, alkaline phosphatase was shown to be the main agent responsible for ecto-AMP nucleotidase activity. In pig renal basolateral membrane vesicles and in whole cell extracts from pig renal cortex, ecto-AMP nucleotidase was the limiting factor in ATP degradation. Comparing the ATP catabolism in the whole cell cortical extract with the catabolism in the same sample precleared of membranes, it was shown that ectonucleotidase activity is mainly bound to the membranous components. It is also shown that the whole cell extract of pig renal cortex has hypoxanthine phosphoribosyl transferase activity, and it seems probable that the rapid and specific formation of luminal inosine and its transport into the cell in competition with adenosine may start the purine salvage pathway through the synthesis of IMP from hypoxanthine.
...
PMID:Adenine nucleotides and adenosine metabolism in pig kidney proximal tubule membranes. 840 44

Methanol-grown Amycolatopsis methanolica NCIB 11946 contains a molybdoprotein dehydrogenase, active with aldehydes and formate esters as substrates and with Wurster's blue as electron acceptor, the so-called formate ester dehydrogenase (FEDH) (van Ophem et al., 1992, Eur. J. Biochem. 206, 519-525). It appears now that another molybdoprotein dehydrogenase is present in this organism. This enzyme, indicated here as dye-linked aldehyde dehydrogenase (DL-AlDH), has the same set of cofactors and converts the same type of substrates but with different specificity, and uses 2,6-dichlorophenol-indophenol as sole artificial electron acceptor for those conversions. The enzymes also differ in their quaternary structure, FEDH having an alpha, beta, gamma and DL-AlDH having an alpha, beta, gamma 2 composition. Furthermore, differences exist with respect to the sizes and the N-terminal amino acid sequences of their subunits, indicating that the enzymes derive from different genes. However, neither their substrate specificity nor their induction pattern give a clear indication for distinct physiological roles. Just like other bacterial molybdoprotein dehydrogenases, DL-AlDH consists of three different subunits (87, 35, and 17 kDa) and contains FAD, molybdopterin-cytosine-dinucleotide cofactor, Fe, and acid-labile sulfide in a molar ratio of 1:1:4:4. Although eukaryotic xanthine oxidase and dehydrogenase differ from these prokaryotic dehydrogenases in size and number of their subunits, certain stretches of amino acid sequences show similarity and the magnetic coupling between the Mo and the [2Fe-2S]-1 cluster in DL-AlDH and bovine milk xanthine oxidase is of the same magnitude. In view of this similarity, the topology of the cofactors in the active site of this type of molybdoproteins might be conserved among enzymes from prokaryotic as well as eukaryotic organisms.
...
PMID:A second molybdoprotein aldehyde dehydrogenase from Amycolatopsis methanolica NCIB 11946. 855 33


1 2 Next >>

---