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

Human spermatozoa possess a specialized capacity to generate reactive oxygen species (ROS) that is thought to be of significance in the redox regulation of sperm capacitation (De Lamirande and Gagnon, 1993; Aitken et al., 1995). However, the mechanisms by which ROS are generated by these cells are not understood. In this study we have examined the possible significance of NADPH as a substrate for ROS production by human spermatozoa. Addition of NADPH to viable populations of motile spermatozoa induced a sudden dose-dependent increase in the rate of superoxide generation via mechanisms that could not be disrupted by inhibitors of the mitochondrial electron transport chain (antimycin A, rotenone, carbonyl cyanide m-chlorophenylhydrazone [CCCP], and sodium azide), diaphorase (dicoumarol) xanthine oxidase (allopurinol), or lactic acid dehydrogenase (sodium oxamate). However, NADPH-induced ROS generation could be stimulated by permeabilization and was negatively correlated with sperm function. Both NADH and NADPH were active electron donors in this system, while NAD+ and NADP+ exhibited little activity. Stereo-specificity was evident in the response in that only the beta-isomer of NADPH supported superoxide production. The involvement of a flavoprotein in the electron transfer process was indicated by the high sensitivity of the oxidase to inhibition by diphenylene iodonium and quinacrine. These results indicate that NAD(P)H can serve as an electron donor for superoxide generation by human spermatozoa and present a simple strategy for the production of motile populations of free radical generating cells with which to study the significance of these molecules in the control of normal and pathological sperm function.
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PMID:Reactive oxygen species generation by human spermatozoa is induced by exogenous NADPH and inhibited by the flavoprotein inhibitors diphenylene iodonium and quinacrine. 921 32

Widespread environmental pollution with mutagenic and carcinogenic nitrofluorenes contributes to human health risks. Since nitroreduction leads to activation of many nitro compounds, nitroreduction of the nitrofluorene (NF) derivatives by one- and two-electron reductants was examined. Rates of nitroreduction catalyzed by xanthine oxidase (XO)/hypoxanthine and measured via stimulation of acetylated cytochrome c reduction increased with the number of nitro groups and oxidation at C-9: 9-oxo-2,4,7-triNF > 9-oxo-2,7-diNF > 2,7-diNF > 9-oxo-2-NF = 2,5-diNF > 9-hydroxy-2-NF > 2-NF. Ascorbate catalyzed one-electron reduction to nitro anion radicals which reacted with molecular O2 to yield superoxide. Rates of O2 uptake with 9-oxo-2,4,7-triNF and 9-oxo-2,7-diNF were 63 and 0.17 times those, respectively, with equivalent concentrations of nitrofurazone, a classical substrate. Superoxide formation was indicated by the approximately 75% regeneration of O2 upon addition of superoxide dismutase and catalase. 9-Oxo-2,4,7-triNF stimulated O2 uptake in the presence of XO/NADH with typical Michaelis-Menten kinetics with an apparent Km of 0.476 +/- 0.054 microM versus a Km of 6.18 +/- 0.719 microM for nitrofurazone. HPLC analyses of products from reduction catalyzed by XO or diaphorase of Clostridium with NADH showed the following trends for the rates of amine formation from 9-oxo-2,7-diNF > 2,7-diNF; 9-oxo-2-NF > 9-hydroxy-2-NF > 2-NF; 2,7-diNF > 2-NF; and 9-oxo-2,7-diNF > 9-oxo-2-NF. Little or no amine was formed in 95% O2, suggesting O2-labile intermediates. The data herein suggest that oxidation at C-9 and multiple nitro groups increase the potential for nitroreduction of the nitrofluorenes in vivo which may lead to genotoxic effects.
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PMID:Nitroreduction of nitrated and C-9 oxidized fluorenes in vitro. 981 98

A specific dehydrogenase, different from nicotinic acid hydroxylase, was induced during growth of Eubacterium barkeri on xanthine. The protein designated as xanthine dehydrogenase was enriched 39-fold to apparent homogeneity using a three-step purification scheme. It exhibited an NADP-dependent specific activity of 164 micromol xanthine oxidized per min and per mg of protein. In addition it showed an NADPH-dependent oxidase and diaphorase activity. A molecular mass of 530 kDa was determined for the native enzyme and SDS/PAGE revealed three types of subunits with molecular masses of 17.5, 30 and 81 kDa indicating a dodecameric native structure. Molybdopterin was identified as the molybdenum-complexing cofactor using activity reconstitution experiments and fluorescence measurements after KI/I2 oxidation. The molecular mass of the cofactor indicated that it is of the dinucleotide type. The enzyme contained iron, acid-labile sulfur, molybdenum, tungsten, selenium and FAD at molar ratios of 17.5, 18.4, 2.3, 1.1, 0.95 and 2.8 per mol of native enzyme. Xanthine dehydrogenase was inactivated upon incubation with arsenite, cyanide and different purine analogs. Reconstitution experiments of xanthine dehydrogenase activity by addition of selenide and selenite performed with cyanide-inactivated enzyme and with chloramphenicol-treated cells, respectively, indicated that selenium is not attached to the protein in a covalently bound form such as selenocysteine.
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PMID:Selenium-containing xanthine dehydrogenase from Eubacterium barkeri. 1049 Nov 34

Nitrofluorenes and C-9-oxidized nitrofluorenes are widespread environmental genotoxins which may be relevant for breast cancer on the basis of their carcinogenicities, particularly of 2, 7-dinitrofluorene (2,7-diNF), for the rat mammary gland. Since their metabolism to active carcinogens may involve nitroreduction, this study examined the reduction of 2-nitrofluorene (2-NF) and 2,7-diNF and their 9-oxo- and 9-hydroxy (OH) derivatives by the rat mammary gland. Cytosolic fractions catalyze NADH- and NADPH-dependent reductions of the 2-nitro and 9-oxo to the respective 2-amino and 9-OH compounds at rates 4- and >/=10-fold greater than those with microsomes. Rates of amine formation catalyzed by cytosol from 2, 7-diNF are greater than the rate from 2-NF and increase for C-9-oxidized derivatives: 9-oxo-2-NF > 9-OH-2-NF > 2-NF and 9-OH-2, 7-diNF >> 9-oxo-2,7-diNF > 2,7-diNF. Nitroreduction is inhibited by O(2) or allopurinol (20 microM), dicoumarol (100 microM), and rutin (50 microM). 9-Oxoreduction is inhibited by rutin, dicoumarol, and indomethacin (100 microM), but not by O(2) or allopurinol. Pyrazole or menadione does not inhibit nitro or 9-oxoreduction. Xanthine, hypoxanthine, 2-hydroxypyrimidine, and N'-methylnicotinamide support cytosol-catalyzed nitro, but not 9-oxo, reduction. The data suggest that the nitroreduction is catalyzed largely by a xanthine oxidase and partially by a diaphorase and 9-oxoreduction by a carbonyl reductase. The extents of the nitro and carbonyl reductions of the nitrofluorenes may determine their reactivities with DNA, and thus genotoxicities for the mammary gland.
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PMID:Reductions of nitro and 9-Oxo groups of environmental nitrofluorenes by the rat mammary gland in vitro. 1095 68

The phenol content and antioxidant activity of extra virgin olive oils (EVOOs) differing in their origins and degradation degrees were studied. The o-diphenolic compounds typical of olive oil, namely, the oleuropein derivatives hydroxytyrosol (3',4'-dihydroxyphenylethanol, 3',4'-DHPEA), the dialdehydic form of elenolic acid linked to 3',4'-DHPEA (3',4'-DHPEA-EDA), and an isomer of oleuropein aglycon (3',4'-DHPEA-EA), were analyzed by HPLC. The antioxidant activity was studied by (a) the xanthine oxidase (XOD)/xanthine system, which generates superoxide radical and hydrogen peroxide; (b) the diaphorase (DIA)/NADH/juglone system, which generates superoxide radical and semiquinonic radical; and (c) the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) test. Results showed that EVOOs with a low degradation level (as evaluated by acidity, peroxide number, and spectroscopic indices K(232), K(270), and deltaK according to the EU Regulation) had a higher content of 3',4'-DHPEA-EDA and a lower content of 3',4'-DHPEA than oils having intermediate and advanced degradation levels. EVOOs with a low degradation degree were 3-5 times more efficient as DPPH scavengers and 2 times more efficient as inhibitors of the XOD-catalyzed reaction than oils with intermediate and advanced degradation levels. The DIA-catalyzed reaction was inhibited by EVOOs having low or intermediate degradation levels but not by the most degraded oils.
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PMID:Comparison of the antioxidant activities of extra virgin olive oils. 1247 92

The principal aim of this study was to assess whether the two quinones, menadione (2-methyl-1,4-naphthoquinone) and lawsone (2-hydroxy-1,4-naphthoquinone), elicit differential toxicity in mussels as has been reported for higher organisms. Therefore, the effects of short-term (48 h) and long-term (20 days) exposure of the two quinones at concentrations of 0.56 and 1 mg l(-1) to zebra mussels, Dreissena polymorpha, under laboratory conditions were studied. After the short-term exposure, the specific activities of the two-electron quinone oxidoreductase (DT-diaphorase) and the one-electron catalysing quinone reductases NADPH-cytochrome c reductase and NADH-cytochrome c reductase were determined in the gills and the rest of the soft tissues (soft mussel tissues minus the gills) of both treated and control mussels. At the higher concentrations of menadione and lawsone used, a significant reduction of the activity of NADPH-cytochrome c reductase in the gills and in the rest of the soft mussel tissues (by 33-34% and 31-43%, respectively) was observed. The activities of DT-diaphorase and NADH-cytochrome c reductase were not significantly affected. Interestingly, DT-diaphorase was observed in the gills, an organ requiring protection against antioxidants. Furthermore, a single-cell electrophoretic assay (comet assay) performed with gill cells to assess DNA damage by the quinones did not show any significant difference between the treated and the control organisms. This indicates that the formation of reactive species by the quinone metabolism in vivo in the mussels was possibly suppressed through the concerted action of DT-diaphorase and antioxidant enzymes. The results of in vitro experiments with gill extracts confirmed the protective role of DT-diaphorase. The rate of the two-electron quinone reduction was found to be five times that of the one-electron quinone reduction. The results of the long-term exposure unambiguously demonstrated that in mussels menadione, unlike in higher organisms, is more toxic than lawsone. The lack of detectability of xanthine oxidase in the mussel tissues could explain the comparatively lower toxicity of lawsone in the invertebtrate, lending support to a previous suggestion that xanthine oxidase might be responsible for the mechanism of toxicity of lawsone in higher organisms in vivo.
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PMID:In vivo exposure of Dreissena polymorpha mussels to the quinones menadione and lawsone: menadione is more toxic to mussels than lawsone. 1505 9

Minimally processed red chicory products (Cichorium intybus L. var. silvestre) were studied for their polyphenol content and antioxidant activity evaluated by using the synthetic 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl radical and three model reactions catalyzed by relevant enzymatic sources of reactive oxygen species, namely, xanthine oxidase, myeloperoxidase, and diaphorase. Products were analyzed at the time of production and after storage at 4 degrees C within either a gas permeable film or a gas barrier film. The antioxidant activity and contents of hydroxycinnamic acids and flavonoids decreased by less than 20% during storage of the minimally processed red chicory products. Total phenolics were significantly correlated with the antioxidant activity evaluated with both the synthetic radical and the enzyme-catalyzed reactions. On a molar basis, red chicory phenolics were as efficient as the reference compound Trolox in scavenging the synthetic radical. However, red chicory phenolics had a much higher inhibitory activity than Trolox in the model enzymatic systems.
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PMID:Antioxidant activity of minimally processed red chicory (Cichorium intybus L.) evaluated in xanthine oxidase-, myeloperoxidase-, and diaphorase-catalyzed reactions. 1868 Mar 76


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