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)

Under anaerobic conditions and with proper electron donors, NADPH-cytochrome P-450 reductase (EC 1.6.2.4) and xanthine oxidase (EC 1.2.3.2) similarly reductively metabolized mitomycin C. Reversed phase high performance liquid chromatography was used to separate, detect, and isolate several metabolites. Three metabolites were identified by mass spectrometry and thin layer chromatography as 1,2-cis- and trans-2,7-diamino-1-hydroxymitosene and 2,7-diaminomitosene. Three metabolites were phosphate-dependent, and two of them were identified to be 1,2-cis- and trans-2,7-diaminomitosene 1-phosphate. The amounts of the five identified metabolites generated during the reduction of mitomycin C varied with pH and nucleophile concentration. At pH 6.5, 2,7-diaminomitosene was essentially the only metabolite formed, whereas from pH 6.8 to 8.0, trans- and cis-2,7-diamino-1-hydroxymitosene increased in quantity as 2,7-diaminomitosene decreased. The disappearance of mitomycin C and the production of metabolites were enzyme and mitomycin C concentration-dependent. Substrate saturation was not reached for either enzyme up to 5 mM mitomycin C. Electron paramagnetic resonance studies demonstrated the formation of mitomycin C radical anion as an intermediate during enzymatic activation. Our results indicate that either enzyme catalyzed the initial activation of mitomycin C to a radical anion intermediate. Subsequent spontaneous reactions, including the elimination of methanol and the opening of the aziridine ring, generate one active center at C-1 which facilitates nucleophilic attack. Simultaneous generation of two reactive centers was not observed. All five primary metabolites were metabolized further by either flavoenzyme. The secondary metabolites exhibited similar changes in their absorbance spectra and were unlike the primary metabolites, suggesting that a second alkylating center other than C-1 was generated during secondary activation. We propose that secondary activation of monofunctionally bound mitomycin C is probably a main route for the bifunctional binding of mitomycin C to macromolecules and that the cytotoxic actions of mitomycin C result from multiple metabolic activations and reactions.
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PMID:Reductive activation of mitomycin C and mitomycin C metabolites catalyzed by NADPH-cytochrome P-450 reductase and xanthine oxidase. 631 93

The activation of N2-methyl-9-hydroxyellipticinium acetate (4) by a peroxidase--H2O2 system leads to the formation of an omicron-quinone (7a). This omicron-quinone is not directly generated from the starting material but through a quinone imine intermediate (6) which is subsequently oxidized. This reaction is highly dependent on pH values. The omicron-quinone 7a is easily protonated (7b), gives an addition product with methanol (9), and is reduced by cysteine. The omicron-quinone 7b has a rather low inhibitory effect against L1210 leukemia cell multiplication but acts as an electron carrier and dramatically augments the oxygen consumption in xanthine oxidase-NADH and rat liver microsomes-NADPH systems.
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PMID:omicron-Quinone formation in the biochemical oxidation of the antitumor drug N2-methyl-9-hydroxyellipticinium acetate. 683 91

Serratia marcecens 2CC-1 utilizes quinaldic acid (quinoline 2-carboxylic acid) as sole source of carbon, nitrogen and energy. Growth of strain 2CC-1 on quinaldic acid as well as on nicotinic acid and hypoxanthine was inhibited completely by the molybdate antagonist tungstate, whereas growth on kynurenic acid and 6-hydroxynicotinic acid was not affected by tungstate. The synthesis of the molybdenum-containing hydroxylases quinaldic acid 4-oxidoreductase and nicotinic acid 6-oxidoreductase was found to be inducible. In addition, Serratia marcescens 2CC-1 produced a constitutively expressed xanthine oxidoreductase. Quinaldic acid 4-oxidoreductase was purified 1075-fold with a recovery of 5%. For catalytic activity, artificial electron acceptors were necessary. The 95-100-kDa enzyme was a heterodimer with subunit molecular masses of 75-80 kDa and 18-19 kDa. Quinaldic acid 4-oxidoreductase contained 2.3-3.7 g atom of iron and 0.5-0.6 g atom of molybdenum per mol of enzyme. The absorption spectrum exhibited maxima at 280 nm, 334 nm, 480 nm and a shoulder at 550 nm, with A280/A334 = 4.8, A280/A450 = 10.0, A280/A480 = 9.4, and A450/A550 = 1.6, suggesting the absence of a flavin cofactor. Acridine, quinacrine, ethylenediaminetetraacetate, 2,2'-dipyridyl, 1,10-phenanthroline and iodoacetate did not affect enzyme activity. p-Hydroxymercuribenzoate, m-arsenite, cyanide and methanol were effective inhibitors of quinaldic acid 4-oxidoreductase. Cyanide-inhibited enzyme was reactivated by treatment with S2-, indicating the presence of a pterin molybdenum cofactor with a monooxo-monosulfidotype molybdenum center. Quinaldic acid 4-oxidoreductase showed a very high substrate specificity, quinaldic acid being the only substrate found to be transformed significantly.
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PMID:Microbial metabolism of quinoline and related compounds. XVIII. Purification and some properties of the molybdenum- and iron-containing quinaldic acid 4-oxidoreductase from Serratia marcescens 2CC-1. 835 32

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.
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PMID:A second molybdoprotein aldehyde dehydrogenase from Amycolatopsis methanolica NCIB 11946. 855 33

In this study, we reported that fatty acid hydroperoxides and hydrogen peroxide are capable of epoxidizing 4-hydroxy-2-nonenal, a lipid peroxidation product, to the mutagenic epoxide. The evidence of its formation is provided (i) by trapping with [8-3H]deoxyadenosine for the formation of 7-(1',2'-dihydroxyheptyl)-1,N6-ethenodeoxyadenosine as a pair of diastereomers, (ii) by derivatization with (2,4-dinitrophenyl)hydrazine in acidic methanol, and (iii) by comparing its 1H-nuclear magnetic resonance and mass spectra to those of the authentic standard. After incubating 4-hydroxy-2-nonenal with 9- or 13-linoleic acid hydroperoxide at 37 degrees C for 24 h, the epoxide was produced in 13.4% or 12.5% yield, and with hydrogen peroxide, the yield was 21.5%. In the presence of fatty acid (linoleic acid, gamma-linolenic acid, or arachidonic acid) and lipoxygenase, the epoxide of 4-hydroxy-2-nonenal was formed in 15.3%, 7.2%, or 6.2% yield, respectively. The xanthine/xanthine oxidase/superoxide dismutase system generated the epoxide in 1.2% yield. These yields are estimated on the basis of a standard curve obtained from reactions of deoxyadenosine and epoxide. These results show that 4-hydroxy-2-nonenal is epoxidized by biological oxidants, suggesting a plausible endogenous pathway for the in vivo formation of etheno adducts.
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PMID:Epoxidation of trans-4-hydroxy-2-nonenal by fatty acid hydroperoxides and hydrogen peroxide. 892 9

We have screened a number of plants from the Indian soil for potential antioxidant properties out of which fifteen extracts were found to be positive. Leaves/bulk from the plants were crushed and extracted with organic solvents by three different ways. The first group of plants were extracted with CHCL3:CH3OH (2:1), evaporated, partitioned between petroleum ether and methanol (9:1), aqueous methanolic part re-partitioned between methanol:H2O (4:1) and dichloromethane. Methanol was evaporated from the aqueous methanolic part and extracted with n-butanol. The second group of plants were extracted with methanol followed by partitioning between petroleum ether and CH3OH. The rest of the extraction procedure was the same as above. A third extraction procedure was used for Ocimum sanctum which after extraction with CHCL3:CH3OH (2:1), partitioned between CCL4 and CH3OH:H2O (9:1). Aqueous methanolic part was repartitioned between CH3OH:H2O (4:1) and CHCl3 and CHCl3 soluble part was used for the study. Free radical scavenging activities of the plant extracts were examined by chemiluminescence method. Peroxyl radical was generated from 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), superoxide radical (O2-) from xanthine/xanthine oxidase (XO) and hydroxyl radical (OH) from Xanthine/XO/FeCl3/ EDTA. In addition, O2- and OH. scavenging activities were also determined by cytochrome C reduction and deoxyribose oxidation methods, respectively. The results of this study demonstrate that these plant extracts possess potent antioxidant activities.
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PMID:Evaluation of antioxidant effectiveness of a few herbal plants. 935 Apr 26

We evaluated free radical scavenging activity of the water, methanol and chloroform extracts of propolis in 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and xanthine-xanthine oxidase (XOD) generated superoxide anion assay systems. The free radical scavenging activity guided fractionation and chemical analysis led to the isolation of a new compound, propol (3-[4-hydroxy-3-(3-oxo-but-1-enyl)-phenyl]-acrylic acid) from the water extract, which was more potent than most common antioxidants such as vitamin C and vitamin E (alpha-tocopherol) in these assay systems.
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PMID:Potent free radical scavenging activity of propol isolated from Brazilian propolis. 946 40

In order to investigate the effects of trace elements on different metabolic pathways, the thermoacidophilic Crenarchaeon Sulfolobus acidocaldarius (DSM 639) has been cultivated on various carbon substrates in the presence and absence of molybdate. When grown on glucose (but neither on glutamate nor casein hydrolysate) as sole carbon source, the lack of molybdate results in serious growth inhibition. By analysing cytosolic fractions of glucose adapted cells for molybdenum containing compounds, an aldehyde oxidoreductase was detected that is present in the cytosol to at least 0.4% of the soluble protein. With Cl2Ind (2,6-dichlorophenolindophenol) as artificial electron acceptor, the enzyme exhibits oxidizing activity towards glyceraldehyde, glyceraldehyde-3-phosphate, isobutyraldehyde, formaldehyde, acetaldehyde and propionaldehyde. At its pH-optimum (6.7), close to the intracellular pH of Sulfolobus, the glyceraldehyde-oxidizing activity is predominant. The protein has an apparent molecular mass of 177 kDa and consists of three subunits of 80.5 kDa (alpha), 32 kDa (beta) and 19.5 kDa (gamma). It contains close to one Mo, four Fe, four acid-labile sulphides and four phosphates per protein molecule. Methanol extraction revealed the existence of 1 FAD per molecule and 1 molybdopterin per molecule, which was identified as molybdopterin guanine dinucleotide on the basis of perchloric acid cleavage and thin layer chromatography. EPR-spectra of the aerobically prepared enzyme exhibit the so-called 'desulpho-inhibited'-signal, known from chemically modified forms of molybdenum containing proteins. Anaerobically prepared samples show both, the signals arising from the active molybdenum-cofactor as well as from the two [2Fe-2S]-clusters. According to metal-, cofactor-, and subunit-composition, the enzyme resembles the members of the xanthine oxidase family. Nevertheless, the melting point and long-term thermostability of the protein are outstanding and perfectly in tune with the growth temperature of S. acidocaldarius (80 degrees C). The findings suggest the enzyme to function as a glyceraldehyde oxidoreductase in the course of the nonphosphorylated Entner-Doudoroff pathway and thereby may attribute a new physiological role to this class of enzyme.
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PMID:The strict molybdate-dependence of glucose-degradation by the thermoacidophile Sulfolobus acidocaldarius reveals the first crenarchaeotic molybdenum containing enzyme--an aldehyde oxidoreductase. 1009 93

Cell-free extract prepared from a mixed culture consisting of strains belonging to the genera Klebsiella and Rhodococcus grown in the presence of caffeine contains a novel enzyme, caffeine (1,3, 7-trimethylxanthine) oxidase which catalyzes the oxidation of caffeine at the C-8 position to produce 1,3,7-trimethyluric acid. The enzyme was purified to homogeneity by a combination of ion-exchange and hydrophobic column chromatographies. Both native and SDS/PAGE of the purified enzyme showed a single protein band and the subunit molecular mass of the protein was determined to be 85 kDa. Dichlorophenol indophenol and cytochrome c served as good electron acceptors but NAD and NADP did not. Caffeine served as the best substrate with an apparent K(m) of 11.4 microM. various analogues of theobromine were also effective substrates for caffeine oxidase. The activity was inhibited by o-phenanthroline, H(2)O(2), and methanol, but salicylate, thiol-group blocking reagents, and sodium arsenite, the known xanthine oxidase inhibitors, did not inhibit the reaction. The spectral characteristics of the purified enzyme suggest that it is a flavoprotein containing non-heme iron.
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PMID:Purification and partial characterization of caffeine oxidase--A novel enzyme from a mixed culture consortium. 1049 16

Heat treatment of Panax ginseng C.A. Meyer at a temperature higher than that applied to the conventional preparation of red ginseng yielded a mixture of saponins with potent antioxidative properties. Thus, the methanol extract of heat-processed neoginseng (designated as 'NGMe') attenuated lipid peroxidation in rat brain homogenates induced by ferric ion or ferric ion plus ascorbic acid. Furthermore, the extract protected against strand scission in phiX174 supercoiled DNA induced by UV photolysis of H2O2, and was also capable of scavenging superoxide generated by xanthine-xanthine oxidase or by 12-O-tetradecanoylphorbol-13-acetate (TPA) in differentiated human promyelocytic leukemia (HL-60) cells. Topical application of NGMe onto shaven backs of female ICR mice 10 min prior to TPA, significantly ameliorated skin papillomagenesis initiated by 7,12-dimethylbenz[a]anthracene. Moreover, TPA-induced enhancement of epidermal ornithine decarboxylase (ODC) activity and ODC mRNA expression was abolished by a topical dose (0.68 mg) of NGMe. Likewise, TPA-induced production of tumor necrosis factor- in mouse skin was inhibited by NGMe pretreatment.
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PMID:Antioxidant and anti-tumor promoting activities of the methanol extract of heat-processed ginseng. 1075 85


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