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)

The effect of an experimental ischemia lasting for 45 minutes and a subsequent period of reperfusion of equal length on the activity of xanthine oxidase (XO) and microsomal NADPH-cytochrome P450 reductase (NADPH-CR) were investigated in the small intestinal mucosa of male neonatal calves of the breed German "Schwarzbunte". The activity of the NADPH-CR was determined by chemiluminescence. The activity of XO decreased during ischemia, but rose to values above the control level following reperfusion. 5 mg of Cu2(succinate)2 (CuSu) administered either intraarterially or intraluminally during reperfusion prevented the rise in XO. Formation of malondialdehyde decreased in the presence of CuSu. The NADPH-CR likewise showed subnormal activity values during ischemia, but also remained at a low level during reperfusion. The activity of this enzyme was further lowered by local intraarterial or intraluminal administration of 5 mg of CuSu and by 120 mg of CuSu administered intravenously during the reperfusion. These results are discussed with regard to the superoxide anion radical induced tissue lesions observed during reperfusion.
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PMID:Investigations on the influence of copper succinate on the production of superoxide anion radicals by bovine small intestinal mucosa cells. 255 59

The lung is especially sensitive to a variety of vastly different agents and conditions including hyperoxia, certain drugs and xenobiotics, particulate debris, and ischemia/reperfusion. There is a growing body of experimental data to suggest that most, if not all, of these agents or conditions mediate pulmonary injury by forming reactive O2 metabolites such as O2-., H2O2.OH, HOCl, and RNHCl. The presence mechanisms by which these different agents converge to produce free radical-mediated pulmonary injury is not entirely clear. The lung does contain several metabolic pathways that will produce large amounts of reactive O2 metabolites. For example, hyperoxia-induced pulmonary injury may be mediated by oxidants produced by both mitochondrial and microsomal electron transport. Certain drugs and xenobiotics may be metabolized by nonspecific flavoproteins found in the mitochondrial electron transport chain and associated with microsomal mixed function oxidase system to yield a variety of free radicals and oxidants. Inhalation of particulate debris will activate resident phagocytic leukocytes to produce large quantities of cytotoxic oxidants. Ischemia and reperfusion appear to produce substantial amounts of xanthine oxidase-derived oxy-radicals that recruit and activate inflammatory phagocytes to produce cytotoxic HOCl and N-chlorinated oxidants. Finally, inappropriate metabolism of arachidonate by prostaglandin synthetase in the presence of NADH (NADPH) produces a burst of O2-. The fact that the lung contains so many different metabolic avenues for oxidant and free radical production suggests that this particular organ may be the most sensitive to oxidative insult.
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PMID:Metabolic sources of reactive oxygen metabolites during oxidant stress and ischemia with reperfusion. 265 Sep 65

The hypoxic cell cytotoxins SR 4233, benznidazole (Benzo), and CB 1954 were readily reduced by anaerobic mouse liver microsomes in vitro to their respective amino or single N-oxide derivatives. The reactions were inhibited in air and required reduced cofactors, particularly NADPH. The rates of reductive bioactivation were markedly different for each drug, with SR 4233 much greater than CB 1954 greater than Benzo. Using purified cytochrome P-450 reductase (P-450 reductase) and an inhibitory antibody to this enzyme, we demonstrated that P-450 reductase was involved in the reductive bioactivation of all 3 compounds. It had a minor role in SR 4233 reduction, but a more important involvement in CB 1954 metabolism to its 4-amino metabolite. Using carbon monoxide, a specific inhibitor of cytochrome P-450 (P-450), we demonstrated that P-450 was involved in both SR 4233 and Benzo reduction. P-450 had a major role both in SR 4233 conversion to SR 4317 and in the latter steps of Benzo amine formation. Purified xanthine oxidase was shown to reduce SR 4233 and Benzo in vitro, but cytosolic aldehyde oxidase activity was only detectable with Benzo as substrate. Characterizing the relative participation of the various reductases in tumor versus normal tissues may allow a more rational selection and application of hypoxic cell cytotoxins in cancer therapy.
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PMID:Molecular enzymology of the reductive bioactivation of hypoxic cell cytotoxins. 270 6

Considerable evidence suggests that the release of iron from ferritin is a reductive process. A role in this process has been proposed for two hepatic enzymes, namely xanthine oxidoreductase and an NADH oxidoreductase. The abilities of xanthine and NADH to serve as a source of reducing power for the enzyme-mediated release of ferritin iron (ferrireductase activity) were compared with turkey liver and rat liver homogenates. The maximal velocity (Vmax.) for the reaction with NADH was 50 times greater than with xanthine; however, the substrate concentration required to achieve half-maximal velocity (Km) was 1000 times less with xanthine than with NADH. NADPH could be substituted for NADH with little loss in activity. Dicoumarol did not inhibit the reaction with NADH or NADPH, demonstrating that the ferrireductase activity with those substrates was not the result of the liver enzyme 'DT-diaphorase' [NAD(P)H dehydrogenase (quinone)]. A flavin nucleotide was required for ferrireductase activity with rat and turkey liver cytosol when xanthine, NADH or NADPH was used as the reducing substrate. FMN yielded twice the activity with NADH or NADPH, whereas FAD was twice as effective with xanthine as substrate. Kinetic comparisons, differences in lability and partial chromatographic resolution of the ferrireductase activities with the two types of reducing substrates strongly indicate that the ferrireductase activities with xanthine and NADH are catalysed by separate enzyme systems contained in liver cytosol. Complete inhibition by allopurinol of the ferrireductase activity endogenous to undialysed liver cytosol preparations and the ability of xanthine to restore equivalent activity to dialysed preparations indicate that the source of reducing power for the endogenous activity is xanthine. These studies suggest that xanthine, NADH or NADPH can serve as a source of reducing power for the enzyme-mediated reduction of ferritin iron, with a flavin nucleotide serving as the shuttle of electrons from the enzymes to the ferritin iron.
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PMID:The mobilization of ferritin iron by liver cytosol. A comparison of xanthine and NADH as reducing substrates. 277 99

Although a number of reducing systems can release iron from ferritin, there is debate as to whether the process additionally requires a chelator. We have studied ferritin iron release by microsomes, paraquat and NADPH, by dialuric acid and by hypoxanthine and xanthine oxidase, using ferrozine to complex the released iron. In each case, Fe2+ (ferrozine) formation was detectable when the ferrozine was added at the beginning of the 10 min reaction period, but not at the end. However, with catalase present, up to 0.7 times as much Fe2+ could be measured with ferrozine added at the end. Further Fe2+ could be recovered by adding ascorbate with the ferrozine. These results indicate that an iron chelator is not required for reductive iron release from ferritin. However, the released iron will not be detectable as Fe2+ unless it forms a complex that is resistant to oxidation by H2O2 or other oxidants.
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PMID:An iron chelator is not required for reductive iron release from ferritin by radical generating systems. 280 53

Uroporphyrin I, haematoporphyrin and haematoporphyrin derivative had no effect on O2-. generation during oxidation of hypoxanthine by xanthine oxidase and on the formation of hydroxyl radicals (OH.) in the hypoxanthine/xanthine oxidase/Fe3+-EDTA/deoxyribose system. On the other hand, these porphyrins strongly inhibited O2-. formation in a horseradish peroxidase/H2O2/NADPH mixture, whereas they augmented OH. generation in this system after addition of Fe3+-EDTA. Experimental evidence suggests that these observations should be ascribed to the formation of a porphyrin anion radical in the horseradish peroxidase/NADPH system. The formation of this anion radical was confirmed by e.s.r. spectroscopy. This radical is apparently unable to reduce cytochrome c, but it can replace O2-. in the OH.-generating Haber-Weiss reaction.
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PMID:The influence of porphyrins on iron-catalysed generation of hydroxyl radicals. 283 35

Methylene blue competes 100 to 600 times more effectively than paraquat for reduction by three different flavo-containing enzymes; xanthine oxidase, NADH cytochrome c reductase, and NADPH cytochrome c reductase. Paraquat and methylene blue both interact with deflavo xanthine oxidase, indicating that neither electron acceptor reacted at the FAD site of the enzyme where molecular oxygen is reduced to superoxide. As the paraquat radical also directly reduced acetylated cytochrome c the hemeprotein could not be utilized for measuring superoxide production in the presence of the herbicide. In the presence of cytochrome c the methylene blue caused a sharp decrease in both paraquat-induced superoxide and hydroxyl radical production.
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PMID:Methylene blue competes with paraquat for reduction by flavo-enzymes resulting in decreased superoxide production in the presence of heme proteins. 283 6

5-(4-Nitrophenyl)penta-2,4-dienal (NPPD) stimulated NADPH-supported oxygen consumption by rat liver microsomes in a concentration-dependent manner. The NPPD stimulation of O2 uptake was not inhibited by metyrapone and was decreased in the presence of NADP+ and p-hydroxymercuribenzoate. These observations suggest that the NPPD initial reduction step is mediated by NADPH-cytochrome P-450 reductase and not by cytochrome P-450. Spin-trapping studies using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) revealed the formation of superoxide anion upon incubation of NPPD, NADPH, DMPO and rat liver microsomes. Hydrogen peroxide generation was also detected in these incubations, thus confirming redox cycling of NPPD under aerobic conditions. NPPD stimulated oxygen consumption, superoxide anion formation and hydrogen peroxide generation by rat kidney, testes and brain microsomes. Other enzymes capable of nitroreduction (NADH dehydrogenase, xanthine oxidase, glutathione reductase, and NADP+ ferredoxin oxidoreductase) were also found to stimulate redox cycling of NPPD. The ability of NPPD to induce superoxide anion and hydrogen peroxide formation might play a role in its reported mutagenicity.
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PMID:Generation of superoxide anion and hydrogen peroxide during redox cycling of 5-(4-nitrophenyl)-penta-2,4-dienal by mammalian microsomes and enzymes. 283 86

Four calcium channel blockers were tested from the point of view of their influence on enzymic lipid oxidation and on generation of superoxide anions. All the compounds were found to be antioxidants as tested by the inhibition of NADPH-stimulated malonaldehyde formation from lipids. IC50 values were 60 microM for nifedipine; 1.1 microM for verapamil; 1.4 microM for fendiline and 20.6 microM for diltiazem. Only nifedipine scavenged superoxide anions both in an enzymic (xanthine:xanthine oxidase) and non-enzymic (phenazine methosulphate:NADH) generating system. IC50 values for this inhibition were about 2.5 times higher than for inhibition of formation of malonaldehyde. Nifedipine inhibited also xanthine oxidase-mediated formation of uric acid.
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PMID:The influence of calcium channel blockers on superoxide anions. 283 71

We postulated that Captopril may be capable of acting as a scavenger of free radicals, and performed in vitro studies using harvested human neutrophils. We studied the effect of Captopril on the reduction of Fe3+ cytochrome c by stimulated PMN's. Captopril acts as a reducing agent in this system, and is capable of reducing Fe3+ cytochrome c by itself. NADPH oxidase was harvested from PMA-stimulated human PMN's. Captopril inhibited the activity of this enzyme as assessed by the disappearance of NADPH determined spectrophotometrically. Since similar inhibition could be demonstrated with the superoxide scavenger superoxide dismutase, further studies were conducted using a DTNB assay of the terminal sulfhydryl group of Captopril, in the presence of a biochemical generator of superoxide (hypoxanthine/xanthine oxidase). We were unable to demonstrate disappearance of the thiol group in this system, suggesting that reaction of the SH group with 02- is unlikely under our conditions. We conclude that Captopril may interfere with human PMN NADPH oxidase in vitro.
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PMID:Captopril--a potential free radical scavenger: inhibition of PMN NADPH oxidase. 284 20


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