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

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

Iron kinetics, absorption and storage were studied by means of 59Fe and deferoxamine (Desferal-Ciba) in eight patients with porphyria cutanea tarda at the time of clinical activity and after allopurinol treatment. At the time of clinical manifestations, a significant impairment of erythrocyte-iron turnover and of radio-iron utilization was demonstrable in a half of the patients and a significant increase in iron absorption and turnover in patients out of 8. The measurements of surface activity in vivo showed a significant increase in storage iron. This was confirmed by the excessive urinary excretion of deferoxamine-iron, attaining three- to four-fold figures of the normal values (251 +/- 85 mg). The increased absorption of iron coupled with an abnormal porphyrin metabolism is suggestive of a double genetic defect. As a result of allopurinol treatment, normalization of iron kinetics and a moderate decrease in iron storage were demonstrable. The abnormal excretion of uroporphyrin and coproporphyrin were also brought under control. The success of treatment is attributed to the inhibitory effect of allopurinol on xanthine oxidase.
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PMID:Iron metabolism and its responses to allopurinol treatment in porphyria cutanea tarda. 74 38

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 study of the participation of metals in evolution of oxidation-reduction processes is subdivided into two periods. During the first of them, from 1897 to 1937, the significance of manganese, iron, titanium, molybdenum, vanadium and copper in most important processes of metabolism was discovered. The second period, from 1937 to 1977, was devoted to the study of the role of metals in individual representatives of oxidoreductases and their evolution during transition of organisms from anaerobiosis to aerobiosis. In this evolution of special importance were bimetallic enzymes, such as nitrogenase, some nitrate reductases and hydrogenases, carbon dioxide reductase, xanthine oxidase, cytochrome oxidase. Owing to their ability to accomplish conjugated oxidation-reduction reactions, these oxidoreductases were transitional to still more complicated polymetallic systems with whose participation the electron transfer chains in subcellular structures were formed.
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PMID:[Participation of polyvalent metals in the evolution of oxidoreductases]. 91 1

Alterations which occur during ischemia are reviewed. They modify the metabolic status in such a way they prepare the cell to an anomalous response to reoxygenation. The consequence of this disturbance is the generation of oxygen free radicals through several mechanisms, including the mitochondrial oxidative phosphorylation, the arachidonic acid cascade, the activation of xanthine oxidase, activation of phagocytes, iron mobilization, etc. Reduced glutathione is exhausted, proteins are inactivated. Lipid peroxidation induces membrane breakdown and cellular death.
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PMID:Ischemia, reperfusion and oxygen free radicals. 129 Jun 47

Xanthine dehydrogenase has been purified to homogeneity by conventional procedures from the wild-type strain of the fruit fly Drosophila melanogaster, as well as from a rosy mutant strain (E89----K, ry5231) known to carry a point mutation in the iron-sulfur domain of the enzyme. The wild-type enzyme had all the specific properties that are peculiar to the molybdenum-containing hydroxylases. It had normal contents of molybdenum, the pterin molybdenum cofactor, FAD, and iron-sulfur centers. EPR studies showed its molybdenum center to be quite indistinguishable from that of milk xanthine oxidase. As isolated, only about 10% of the enzyme was present in the functional form, with most or all of the remainder as the inactive desulfo form. It is suggested that this may be present in vivo. Extensive proteolysis accompanied by the development of oxidase activity took place during isolation, but dehydrogenase activity was retained. EPR properties of the reduced iron-sulfur centers, Fe-SI and Fe-SII, in the enzyme are very similar to those of the corresponding centers in milk xanthine oxidase. The E89----K mutant enzyme variant was in all respects closely similar to the wild-type enzyme, with the exception that it lacked both of the iron-sulfur centers. This was established both by its having the absorption spectrum of a simple flavoprotein and by the complete absence of EPR signals characteristic of iron-sulfur centers in the reduced enzyme. Despite the lack of iron-sulfur centers, the mutant enzyme had xanthine:NAD+ oxidoreductase activity indistinguishable from that of the wild-type enzyme. Stopped-flow measurements indicated that, as for the wild-type enzyme, reduction of the mutant enzyme was rate-limiting in turnover. Thus, the iron-sulfur centers appear irrelevant to the normal turnover of the wild-type enzyme with these substrates. However, activity to certain oxidizing substrates, particularly phenazine methosulfate, is abolished in the mutant enzyme variant. This is one of the first examples of deletion by genetic means of iron-sulfur centers from an iron-sulfur protein. The relevance of our findings both to the roles of iron-sulfur centers in other systems and to the nature of the oxidizing substrate for the Drosophila enzyme in vivo are briefly discussed.
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PMID:Xanthine dehydrogenase from Drosophila melanogaster: purification and properties of the wild-type enzyme and of a variant lacking iron-sulfur centers. 131 86

Two free radical generating systems, xanthine oxidase/hypoxanthine or phenazine methosulfate/NADH, were exposed to air plus He, N2, or Ar at partial pressures ranging from 0.2 to 6.0 MPa, and the rates of production of superoxide, hydroxyl, singlet O2, and H2O2 were measured. All three inert gases acted similarly to enhance the production of superoxide radicals by facilitating interactions between iron and H2O2, or O2 and organic radicals. These reactions occurred at quite low gas partial pressures, only 0.28 MPa, and hydrostatic pressures of up to 6.0 MPa had no effect on radical reactions. Enhanced radical production may be the basis for the inhibition of cellular growth mediated by inert gases, and inert gas enhancement of O2 toxicity.
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PMID:Inert gas enhancement of superoxide radical production. 131 38

Previous studies have shown that heparin antagonizes oxygen radical-mediated injury to endothelial cells, suggesting an antioxidant role of the drug. In the present investigation, the hypothesis that heparin exerts direct antioxidant effects was tested in several experimental models. We have found that 1, 3, 5, 10, 20, 40 and 80 U/mL of heparin do not scavenge superoxide anion, hydrogen peroxide, hydroxyl radical or the stable free radical 1,1-diphenyl-2-pycrylhydrazyl. Moreover, the drug is ineffective towards iron-driven linolenic acid peroxidation, autooxidation of brain homogenate and linolenic acid peroxidation mediated by human internal mammary artery homogenate. Specific studies on the potential iron-binding-inactivating capacity of heparin prove the drug to be totally ineffective. Finally, the loss of protein sulphydryls from human plasma induced by hypoxanthine-xanthine oxidase-generated oxygen radicals is not prevented by heparin. In conclusion, heparin, even at concentrations far higher than those usually used therapeutically, has no direct antioxidant properties. Thus, other mechanisms not strictly antioxidant-type must be involved in heparin-mediated cell protection against toxic oxygen metabolites.
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PMID:Heparin: does it act as an antioxidant in vivo? 132 28

We examined the protective effect of cellular superoxide dismutase against extracellular hydrogen peroxide in cultured bovine aortic endothelial cells. 51Cr-labeled cells were exposed to hydrogen peroxide generated by glucose oxidase/glucose. Glucose oxidase caused a dose-dependent increase of 51Cr release. Pretreatment with diethyldithiocarbamate enhanced injury induced by glucose oxidase, corresponding with the degree of inhibition of endogenous superoxide dismutase activity. Inhibition of cellular superoxide dismutase by diethyldithiocarbamate was not associated either with alteration of other antioxidant defenses or with potentiation of nonoxidant injury. Enhanced glucose oxidase damage by diethyldithiocarbamate was prevented by chelating cellular iron. Inhibition of cellular xanthine oxidase neither prevented lysis by hydrogen peroxide nor diminished enhanced susceptibility by diethyldithiocarbamate. These results suggest that, in cultured endothelial cells: 1) cellular superoxide is involved in mediating hydrogen peroxide-induced damage; 2) superoxide, which would be generated upon exposure to excess hydrogen peroxide independently of cellular xanthine oxidase, promotes the Haber-Weiss reaction by initiating reduction of stored iron (Fe3+) to Fe2+; 3) cellular iron catalyzes the production of a more toxic species from these two oxygen metabolites; 4) cellular superoxide dismutase plays a critical role in preventing hydrogen peroxide damage by scavenging superoxide and consequently by inhibiting the generation of the toxic species.
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PMID:Role of cellular superoxide dismutase against reactive oxygen metabolite injury in cultured bovine aortic endothelial cells. 132 16

The nitrovasodilator, nicorandil, is a clinically effective antianginal agent. We tested whether nicorandil may also possess anti-free-radical characteristics, since the nicotinamide moiety of its molecular structure is a known hydroxyl radical scavenger. In vitro production of hydroxyl radicals by hypoxanthine plus xanthine oxidase in the presence of iron produced a marked degradation of deoxyribose. Nicorandil and the structural analogs, nicotinic acid and nicotinamide, produced significant inhibition of deoxyribose breakdown at concentrations equipotent to the classical hydroxyl radical scavenger, mannitol. Nicorandil also produced a concentration-dependent inhibition of superoxide anion production by canine neutrophils that were activated with either phorbol myristate acetate (PMA) or opsonized zymosan. This inhibition could not be mimicked by the analog, nicotinamide. While equimolar concentrations of nitroglycerin produced less inhibition of superoxide anion generation in opsonized zymosan-activated neutrophils than that observed with nicorandil, nitroglycerin did not alter free-radical production in PMA-stimulated neutrophils. Glyburide, the ATP-sensitive potassium-channel blocker, did not reverse the action of nicorandil on neutrophils. Thus, nicorandil is a uniquely different nitrovasodilator with anti-free-radical and neutrophil-modulating properties.
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PMID:Anti-free-radical and neutrophil-modulating properties of the nitrovasodilator, nicorandil. 132 63

Diphenylene iodonium (Ph2I), a lipophilic reagent, is an efficient inhibitor of the production of O2- by the activated NADPH oxidase of bovine neutrophils. In a cell-free system of NADPH oxidase activation consisting of neutrophil membranes and cytosol from resting cells, supplemented with guanosine 5'-[gamma-thio]triphosphate, MgCl2 and arachidonic acid, or in membranes isolated from neutrophils activated by 4 beta-phorbol 12-myristate 13-acetate, addition of a reducing agent, e.g. NADPH or sodium dithionite, markedly enhanced inhibition of the NADPH oxidase by Ph2I. The membrane fraction was found to contain the Ph2I-sensitive component(s). In the presence of a concentration of Ph2I sufficient to fully inhibit O2- production (around 10 nmol/mg membrane protein), addition of catalytic amounts of the redox mediator dichloroindophenol (Cl2Ind) resulted in a by-pass of the electron flow to cytochrome c, the rate of which was about half of that determined in non-inhibited oxidase. A marked increase in the efficiency of this by-pass was achieved by addition of sodium deoxycholate. The Cl2-Ind-mediated cytochrome c reduction was negligible in membranes isolated from resting neutrophils. At a higher concentration of Ph2I (100 nmol/mg membrane protein), the Cl2Ind-mediated cytochrome c reductase activity was only half inhibited, which indicated that, in the NADPH oxidase complex, there are at least two Ph2I sensitive components, differing by their sensitivity to the inhibitor. At low concentrations of Ph2I (less than 10 nmol/mg protein), the spectrum of reduced cytochrome b558 in isolated neutrophil membranes was modified, suggesting that the component sensitive to low concentrations of Ph2I is the heme binding component of cytochrome b558. Higher concentrations of Ph2I were found to inhibit the isolated NADPH dehydrogenase component of the oxidase complex. A number of membrane and cytosolic proteins were labeled by [125I]Ph2I. However, the radiolabeling of a membrane-bound 24-kDa protein, which might be the small subunit of cytochrome b558, responded more specifically to the conditions of activation and reduction which are required for inhibition of O2- production by Ph2I. The O2(-)-generating form of xanthine oxidase was also inhibited by Ph2I. Inhibition of xanthine oxidase, a non-heme iron flavoprotein, by Ph2I had a number of features in common with that of the neutrophil NADPH oxidase, namely the requirement of reducing conditions for inhibition of O2- production by Ph2I and the induction of a by-pass of electron flow to cytochrome c by Cl2Ind in the inhibited enzyme, suggesting some similarity in the molecular organization of the two enzymes.
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PMID:Diphenylene iodonium as an inhibitor of the NADPH oxidase complex of bovine neutrophils. Factors controlling the inhibitory potency of diphenylene iodonium in a cell-free system of oxidase activation. 132 36


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