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 synthesis of 1H-pyrrolo[3,2-c]pyridine-4,6(5H,7H)-dione (3,7-dideazaxanthine) (1), 5-methyl-1H-pyrrolo-[3,2-c]pyridine-4,6(5H,7H)-dione (1-methyl-3,7-dideazaxanthine) (2), and 1,7-dihydropyrano[4,3-b]pyrrole-4,6-dione (1-oxa-1,3,7-trideazaxanthine) (3) has been accomplished from 3-alkoxycarbonylpyrrole-2-acetates (4, 11, and 12 for 1 and 2) and from 3-carboxypyrrole-2-acetic acid (6 for 3). Compounds 1 and 2 have been found to be weak inhibitors of the noncompetitive type for xanthine oxidase while 3 showed no inhibitory properties toward this enzyme.
 ...
PMID:Synthesis and xanthine oxidase inhibitory analysis of 1H-pyrrolo[3,2-c]pyridine-4,6(5H,7H)-dione (3,7-dideazaxanthine) and two of its derivatives. 72 64

1-, 3-, and 5-substituted pyrazolo[3,4-d]pyrimidines and pyrazolo[3,4-b]pyridines related to allopurinol were synthesized and evaluated as xanthine oxidase inhibitors. Among these compounds, 4-hydroxypyrazolo[3,4-b]pyridine-5-carboxylic acids 12 were found to possess potency in the same order of allopurinol. The influence of the substitutions on the enzyme inhibitory effect and the bulk tolerance of the enzyme-inhibitor complex are discussed.
 ...
PMID:Synthesis and biological evaluation of xanthine oxidase inhibitors. Pyrazolo(3,4-d)pyrimidines and pyrazolo(3,4-b)pyridines. 112 Sep 82

X-ray spectroscopy was used to provide further information on the structure of the molybdenum centre of xanthine oxidase. Earlier work was confirmed and two states of the enzyme, not reported on by previous workers, were studied. One of these was the complex of the enzyme with pyridine-3-carboxaldehyde, in which most of the metal is in the Mo(V) state, giving the e.p.r. signal known as Inhibited. The other was the complex with the inhibitor alloxanthine, with the metal as Mo(IV). For both complexes clear evidence was obtained that an oxo ligand of molybdenum was present, but not a sulphido ligand. This information complements structural information on these complexes already available from e.p.r. spectroscopy, and has permitted us to revise and refine the structures previously proposed. The mechanism of action of the enzyme is discussed in the light of the present findings on the persistence of the oxo group in the reduced enzyme complexes, as well as of related evidence [George & Bray (1988) Biochemistry 27, 3603-3609] for an oxo group in the catalytic intermediate that gives the Mo(V) e.p.r. signal known as Very Rapid.
 ...
PMID:Information from e.x.a.f.s. spectroscopy on the structures of different forms of molybdenum in xanthine oxidase and the catalytic mechanism of the enzyme. 276 89

Sulfasalazine suppresses mucosal injury in patients with ulcerative colitis, but the mechanism of its therapeutic action is uncertain. In the present study, we examined the mechanism of the protective action of sulfasalazine in a rat model in which colonic epithelial cell loss and subsequent increases in epithelial proliferative activity were induced by intracolonic instillation of sodium deoxycholate. Sulfasalazine or its therapeutically active metabolite 5-aminosalicylic acid suppressed the loss of deoxyribonucleic acid into the colonic lumen and the subsequent increases in mucosal ornithine decarboxylase activity and tritiated thymidine incorporation into deoxyribonucleic acid induced by sodium deoxycholate. Sulfasalazine and 5-aminosalicylic acid also blocked xanthine-xanthine oxidase-induced loss of deoxyribonucleic acid and the subsequent proliferative response. In vitro sodium deoxycholate increased reactive oxygen formation by colonic mucosal scrapings or isolated crypt epithelium. These actions of sodium deoxycholate on reactive oxygen formation were blocked by sulfasalazine or 5-aminosalicylic acid. Sulfapyridine, a therapeutically inactive metabolite of sulfasalazine, had no effect on sodium deoxycholate-induced increases in surface cell sloughing, ornithine decarboxylase, tritiated thymidine incorporation into deoxyribonucleic acid, chemiluminescence, or superoxide production. The ability of sulfasalazine and 5-aminosalicylic acid to scavenge reactive oxygen may play a role in their therapeutic effects of inflammatory bowel disease.
 ...
PMID:Actions of sulfasalazine and 5-aminosalicylic acid as reactive oxygen scavengers in the suppression of bile acid-induced increases in colonic epithelial cell loss and proliferative activity. 288 67

Reduced nicotinamide adenine dinucleotide (NADH):ferricyanide reductase and DT-diaphorase specific activity in total homogenates of rat liver are markedly decreased as a very early biochemical event of hepatocarcinogenesis induced by the carcinogen 2-acetylaminofluorene (AAF). A 50 to 75% decrease in NADH:ferricyanide reductase was observed after 1 day of AAF (0.025% in the diet) feeding and persisted throughout a 7-week continuum of AAF administration. Carcinogen added directly to cell extracts had no effect. Similar results were obtained with single injections of either AAF or diethylnitrosamine. Xanthine dehydrogenase was also reduced in liver following AAF administration to nearly the same extent as NADH:ferricyanide reductase and DT-diaphorase. Total NADH-cytochrome c reductase and mitochondrial activity as estimated from succinic dehydrogenase were not affected by carcinogen administration relative to basal dietary controls. The reduced nicotinamide adenine dinucleotide phosphate:cytochrome c reductase that functions in drug detoxification was elevated. With livers of animals fed 4-acetamidophenol, a hepatotoxin chemically related to AAF, small decreases were noted in NADH:ferricyanide reductase, but not in xanthine dehydrogenase nor in DT-diaphorase. Initial lowering of these activities in the livers of the carcinogen-treated animals is preceded by or concomitant with a reduction in the levels of extramitochondrial pyridine nucleotides known from other studies to result from DNA damage.
 ...
PMID:Decreased NADH-oxidoreductase activities as an early response in rat liver to the carcinogen 2-acetylaminofluorene. 396 29

The catalytic oxidation of [14C]-formate to 14CO2 was adapted to measure H2O2 formation in cellfree system. Standard curves employing glucose-glucose oxidase and xanthine-xanthine oxidase demonstrated linearity between 14CO2 evolution and enzyme concentration. A particulate fraction from human neutrophils was capable of oxidizing [14C]-formate; this reaction was dependent upon the presence of catalase, reduced pyridine nucleotide, and cellular material. Reaction increased with time of incubation and protein concentration, although not in a strictly linear fashion. The pH optimum was approximately 5.5 NADPH was a significantly better substrate than NADH, although both were capable of generating H2O2. The particulate fraction derived from phagocytizing cells was more active than a corresponding fraction from resting cells with either substrate. H2O2 production was abnormal in particulate fractions derived from 2 patients with chronic granulomatous disease. H2O2 production was markedly inhibited by superoxide dismutase or cytochrome c (scavengers of superoxide anion) but not by scavengers of singlet oxygen or hydroxyl radical. Reaction was greatly stimulated by the addition of manganous ion. These results are consistent with the hypothesis that the respiratory burst in human neutrophils is initiated by an oxidase that can utilize either NADPH or NADH but exhibits a marked preference for the former. Further, the inhibitor studies strongly support a mechanism involving an initial enzymatic reaction followed by a self-sustaining free radical reaction involving superoxide anion.
 ...
PMID:Pyridine nucleotide-dependent generation of hydrogen peroxide by a particulate fraction from human neutrophils. 689 95

The kinetics of the oxidative half-reaction between reduced thioredoxin reductase and oxidized thioredoxin measured in the presence and absence of pyridine nucleotide show a significant difference in the rates of the main phase of oxidation. When 1 equiv of NADPH is used to partially reduce the enzyme at pH 7.0 or 7.6, the observed rate of the catalytically competent phase of oxidation is essentially equal to kcat at that pH. This is about 50% of the rate of oxidation observed with enzyme fully reduced or partially reduced by the xanthine/xanthine oxidase system or by dithionite. Through the use of the nonreducible analog 3-aminopyridine adenine dinucleotide phosphate we have shown that this decrease in observed rate of oxidation is linked to the concentration of pyridine nucleotide present. This suggests that the complexation of pyridine nucleotides with reduced thioredoxin reductase is able to effect a change in the rate-limiting steps of the oxidation of the enzyme by thioredoxin. This is the case even when substoichiometric quantities of 3-aminopyridine adenine dinucleotide phosphate are present, which predicts that the binding to reduced enzyme is very tight. It is clear that the presence of 1 equiv of NADP+ is sufficient to cause the observed rate for the catalytically competent phase of oxidation to decrease to kcat. Thus, there is compelling evidence for a ternary complex mechanism for thioredoxin reductase.
 ...
PMID:Effect of pyridine nucleotide on the oxidative half-reaction of Escherichia coli thioredoxin reductase. 789 63

This study was designed to investigate the effects of prostaglandin E1 on reductive stress and the subsequent oxidative cell injury in hypoperfused rat liver. The intralobular heterogeneity of hepatocellular redox state, mitochondrial dysfunction, and intracellular hydroperoxide formation were visually monitored by digital microfluorography of pyridine nucleotide autofluorescence, rhodamine 123, and dichlorofluorescein fluorescence, respectively. Under the 25% low flow perfusion, pyridine nucleotide autofluorescence increased time-dependently and reached a steady state at 10 min among the entire lobules. The decrease in mitochondrial membrane potential was > 20 mV in all portions of the lobules at 60 min. The onset of hydroperoxide formation was observed at 40 min in the marginally oxygenated proximal portion of anoxic pericentral regions and the oxidative impact reached a maximum level at 60 min. Sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazo [1,5-a]-1,3,5-triazine-4-olate monohydrate (BOF 4272), a novel xanthine oxidase inhibitor, suppressed the zone-specific oxidative changes without attenuating the increase in pyridine nucleotide autofluorescence and mitochondrial dysfunction. Pretreatment with prostaglandin E1 not only abrogated an early increase in pyridine nucleotide fluorescence and mitochondrial dysfunction induced by hypoperfusion but also diminished the subsequent midzonal oxidative injury. Since prostaglandin E1 has no oxyradical-scavenging action, the preventive effect of this reagent on the hypoxia-induced oxidative cell injury is attributable to the attenuation of mitochondrial dysfunction. These results suggest that, in low flow hypoxia, early reductive stress plays a key role in the initiation of xanthine oxidase-mediated midzonal oxidative changes, which may lead to subsequent centrilobular necrosis.
 ...
PMID:Prostaglandin E1 abrogates early reductive stress and zone-specific paradoxical oxidative injury in hypoperfused rat liver. 828 82

Reoxygenation of rat-liver mitochondria after anoxic incubation induced release of matrix proteins. As assessed by release of a matrix enzyme, it was proportional to the rate of H2O2 production. The release was not observed with low concentrations of extramitochondrial free Ca2+, indicating a Ca(2+)-dependent pathway. Phospholipase A2 was not involved in the reoxygenation injury, because non-esterified fatty acids did not increase on reoxygenation even when re-acylation was inhibited and because inhibitors of phospholipase A2 had little effect on enzyme release. Cyclosporin A, ATP, ADP and inhibitors of pyridine nucleotide oxidation had a protective effect, strongly suggesting involvement of so-called Ca(2+)-dependent permeability transition. Ca2+ was also released from reoxygenated mitochondria and inhibition of reuptake of released Ca2+ attenuated the enzyme release. Similar releases of aspartate aminotransferase and Ca2+ were observed with mitochondria in an oxygen radical-generating system, hypoxanthine and xanthine oxidase. In this system, lecithin-cardiolipin liposomes also released entrapped Ca2+ without disruption of the membrane. From these results, we conclude that during reoxygenation, Ca2+ release and subsequent reuptake induced permeability transition of mitochondria, resulting in reoxygenation injury.
 ...
PMID:Ca(2+)-induced, phospholipase-independent injury during reoxygenation of anoxic mitochondria. 841 80

Mixed ligand complexes of copper polyamine with biomolecules such as imidazole, substituted imidazoles or pyridine have been synthesized and characterized. These molecules were used because of their low toxicity and high activity. These complexes were found to possess a distorted octahedral microenvironment with a potential SOD mimicking activity. The IC50 values for these complexes were of the order of 2-90 microM. Pyridine and imidazole complexes were most effective as they possess the lowest IC50 values of 2.1 and 6 microM respectively which are higher than the IC50 value of polyamine copper complex. Based on the uric acid estimations, it has also been ascertained that these complexes dismute O2- without inhibiting xanthine oxidase activity. The presence of increasing concentrations of albumin had no effect on the SOD mimicking activity of mixed ligand complexes. Polyamine complex, however lost approximately 80% of SOD mimicking activity in the presence of albumin (1 mg). These results suggest that coordination of polyamine copper complex with imidazoles/pyridine may abolish their binding affinity for albumin while potentiating their SOD mimicking activity.
 ...
PMID:Coordination of copperpolyamine complex with imidazoles potentiates it superoxide dismutase mimicking activity and abolishes its interaction with albumin. 884 51


1 2 3 Next >>