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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxygen free radicals may be generated during ethanol metabolization by cytochrome P450, or due to the formation of xanthine oxidase by ethanol effect on xanthine dehydrogenase. After transformation into acetaldehyde, the metabolism of this compound by xanthine oxidase or by aldehyde oxidase also generates oxygen radicals. We present the hypothesis of a vicious cycle during ethanol metabolization by aldehyde oxidase, which would amplify the process and be responsible for an increased degree of lipid peroxidation.
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PMID:[Alcohol and free oxygen radicals]. 839 65

--2-(Dimethylamino) fluorene (1a) and 5-benzoyloxy-2,3,7,8,12,13,17,18-octaethylporphyrin (4) react with superoxide anion radical (generated from KO2/18-crown-6 polyether) in aprotic media. Yet, when incorporated into the lipid bilayer of dimyristoyl phosphatidylcholine liposomes, these two substrates are inert to superoxide, generated enzymatically (xanthine oxidase/acetaldehyde) or radiolytically (60Co or 137Cs source/formate solution). On the other hand, 7-acetoxy-4-methylcoumarin (6), which reacts with superoxide in aprotic media yielding the corresponding 4-methylumbelliferone (7), also gives the same product when incorporated within the liposomal bilayer and reacted with radiolytically or enzymatically generated superoxide. In the latter case, the reaction is inhibited by SOD. NMR studies indicate that in contradistinction to the highly lipophilic 1a and 4, which presumably lie well within the lipid bilayer, 7 lies in a highly polar region of the bilayer. These results suggest that superoxide anion does not penetrate deep into the liposomal bilayer; nevertheless, superoxide reactions can, indeed, be observed, provided the active site of the substrate lies at or near the lipid-water interface.
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PMID:Can superoxide organic chemistry be observed within the liposomal bilayer? 872 33

Reactive oxygen species are involved in luminol chemiexcitation induced in biological systems, but the contribution of nitrogen-derived oxidants in the process still remains unclear. Herein, we report that luminol chemiluminescence (LCL) induced by a superoxide (O2.-)- and hydrogen peroxide (H2O2)-generating system (2-25 mU/ml xanthine oxidase plus acetaldehyde and oxygen) was markedly inhibited by nitric oxide (.NO) added either as bolus (0-10 microM) or a continuous flow (0-10 microM/min). However, the inhibition of LCL was followed by an overshoot in light emission after most .NO was consumed or the infusion stopped and was due to reactions of remaining peroxynitrite, the product of the reaction between O2.- and .NO, with luminol. Nitric oxide also inhibited peroxynitrite- and glucose oxidase-induced LCL, but no overshoot was observed. On the other hand, a continuous flux of pure peroxynitrite, at 2 to 10 microM/min, induced LCL with quantum yields close to those obtained by identical micromolar fluxes of O2.-, while peroxynitrite formed from the decomposition of the sydnonimine SIN-1 yielded 76% of the chemiluminescence obtained with authentic peroxynitrite. Peroxynitrite-induced LCL was 80 and 55% inhibitable by SOD and catalase, respectively, showing that there were O2.- and H2O2-dependent routes of chemiexcitation. The hydroxyl radical scavengers dimethyl sulfoxide, mannitol, and ethanol and the metal chelator diethylenetriaminepentaacetic acid did not inhibit peroxynitrite-induced LCL while desferrioxamine was an efficient inhibitor of light emission by reaction with an activated state of peroxynitrous acid which is responsible of performing the initial one-electron oxidation of luminol. Our results are consistent with a dual role of .NO in O2.(-)-induced LCL: (I) formation of peroxynitrite which in turn promotes the light-emitting route and (II) reaction with luminol radical intermediates directing the system toward a dark pathway. These considerations are of critical importance when analyzing cell- and tissue-derived LCL in .NO-, O2.(-)-, and peroxynitrite-producing systems.
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PMID:Modulatory role of nitric oxide on superoxide-dependent luminol chemiluminescence. 880 69

The main pathway for the hepatic oxidation of ethanol to acetaldehyde proceeds via ADH and is associated with the reduction of NAD to NADH; the latter produces a striking redox change with various associated metabolic disorders. NADH also inhibits xanthine dehydrogenase activity, resulting in a shift of purine oxidation to xanthine oxidase, thereby promoting the generation of oxygen-free radical species. NADH also supports microsomal oxidations, including that of ethanol, in part via transhydrogenation to NADPH. In addition to the classic alcohol dehydrogenase pathway, ethanol can also be reduced by an accessory but inducible microsomal ethanoloxidizing system. This induction is associated with proliferation of the endoplasmic reticulum, both in experimental animals and in humans, and is accompanied by increased oxidation of NADPH with resulting H2O2 generation. There is also a concomitant 4- to 10-fold induction of cytochrome P4502E1 (2E1) both in rats and in humans, with hepatic perivenular preponderance. This 2E1 induction contributes to the well-known lipid peroxidation associated with alcoholic liver injury, as demonstrated by increased rates of superoxide radical production and lipid peroxidation correlating with the amount of 2E1 in liver microsomal preparations and the inhibition of lipid peroxidation in liver microsomes by antibodies against 2E1 in control and ethanol-fed rats. Indeed, 2E1 is rather "leaky" and its operation results in a significant release of free radicals. In addition, induction of this microsomal system results in enhanced acetaldehyde production, which in turn impairs defense systems against oxidative stress. For instance, it decreases GSH by various mechanisms, including binding to cysteine or by provoking its leakage out of the mitochondria and of the cell. Hepatic GSH depletion after chronic alcohol consumption was shown both in experimental animals and in humans. Alcohol-induced increased GSH turnover was demonstrated indirectly by a rise in alpha-amino-n-butyric acid in rats and baboons and in volunteers given alcohol. The ultimate precursor of cysteine (one of the three amino acids of GSH) is methionine. Methionine, however, must be first activated to S-adenosylmethionine by an enzyme which is depressed by alcoholic liver disease. This block can be bypassed by SAMe administration which restores hepatic SAMe levels and attenuates parameters of ethanol-induced liver injury significantly such as the increase in circulating transaminases, mitochondrial lesions, and leakage of mitochondrial enzymes (e.g., glutamic dehydrogenase) into the bloodstream. SAMe also contributes to the methylation of phosphatidylethanolamine to phosphatidylcholine. The methyltransferase involved is strikingly depressed by alcohol consumption, but this can be corrected, and hepatic phosphatidylcholine levels restored, by the administration of a mixture of polyunsaturated phospholipids (polyenylphosphatidylcholine). In addition, PPC provided total protection against alcohol-induced septal fibrosis and cirrhosis in the baboon and it abolished an associated twofold rise in hepatic F2-isoprostanes, a product of lipid peroxidation. A similar effect was observed in rats given CCl4. Thus, PPC prevented CCl4- and alcohol-induced lipid peroxidation in rats and baboons, respectively, while it attenuated the associated liver injury. Similar studies are ongoing in humans.
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PMID:Role of oxidative stress and antioxidant therapy in alcoholic and nonalcoholic liver diseases. 889 26

Xanthine oxidase (XO), catalyzes the sequential oxidation of hypoxanthine to xanthine and then to uric acid. The enzyme also catalyzes the oxidation of aldehydes to their corresponding carboxylic acids. In the present work we investigate the extent of inhibition of the xanthine oxidase-catalyzed oxidation of hypoxanthine by acetaldehyde/acetaldehyde hydrate system. At room temperature, aqueous solutions of acetaldehyde exist as equilibrated mixtures containing similar quantities of the aldehyde, CH3CHO and its hydrate CH3CH(OH)2. To determine whether acetaldehyde or its hydrate interacts with the enzyme to cause inhibition, the time course of enzymatic inhibition was observed in deoxygenated solutions of xanthine oxidase initially incubated with neat acetaldehyde and compared to that in which the enzyme was initially incubated with aqueous solutions containing both the aldehyde and its hydrate. Our results show that unhydrated acetaldehyde inhibits XO and that the inhibition of the XO-catalyzed oxidation of hypoxanthine progressively increases as the aldehyde is incubated with the enzyme. The data, taken together, suggest that enzymatic inhibition is the result of the reversible formation of covalently bound XO-acetaldehyde inhibitory compound. This investigation also demonstrates that the enzymatic oxidations of hypoxanthine and acetaldehyde take place on the same active site in XO.
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PMID:The inhibition of xanthine oxidase by acetaldehyde in aqueous solution. 909 92

We have discussed in this review many features and possible mechanisms responsible for the development of alcoholic cardiomyopathy. The evidence suggests that defects in myofibrillar protein turnover occur in both acute and chronic alcohol studies. Possible mechanisms to explain poor contractile function include alterations in cellular calcium, magnesium or phosphate homeostasis. The toxic effects of acetaldehyde or the formation of fatty acid ethyl esters may cause impairment of mitochondrial oxidative phosphorylation. Alternatively, reduced amounts of heat shock proteins may result in poor assembly and protection of proteins. In acute ethanol toxicity ischaemia may occur, possibly due to increased xanthine oxidase activity or beta-adrenergic stimulation. Chronic alcohol consumption can also lead to the development of hypertension via magnesium loss and consequent alterations in peripheral vascular calcium regulation. However, these are only a few facets of a complex relationship between alcohol and the cardiovascular system.
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PMID:The effects of alcohol on the heart. 919 55

We studied microbicidal activities of reactive nitrogen intermediates (RNI), free fatty acids (FFA), and reactive oxygen intermediates (ROI) against Mycobacterium avium complex (MAC) and the mode of macrophage (mphi) production of these effectors. (1) Intracellular growth of MAC in murine peritoneal mphis was accelerated by scavengers for ROI or RNI and inhibitors of nitric oxide synthase or phospholipase A2, indicating roles of ROI, RNI, and FFA in mphi anti-MAC functions. (2) Acidified NaNO2-derived RNI, FFA (linolenic and arachidonic acids), and the H2O2-mediated halogenation system exhibited a significant anti-MAC bactericidal activity. The combination of RNI with FFA showed a synergistic effect. However, the H2O2-halogenation system in combination with either RNI or FFA showed an antagonism. When Listeria monocytogenes (Lm) was used as a target organism, the combinations of RNI + FFA and RNI + H2O2-halogenation gave a synergistic effect, whereas FFA + H2O2-halogenation showed an antagonism in exerting bactericidal activity. In addition, when ROI generated by the xanthine oxidase-acetaldehyde system was combined with RNI, anti-Lm but not anti-MAC activity was potentiated. (3) ROI production by murine peritoneal mphis was observed immediately after contact with MAC organisms (MAC stimulation) and ceased within 2 h. FFA release was seen 1-24 h after MAC stimulation. RNI production was initiated from 3 h and increased during the first 36 h and continued at least for 4 days. These findings suggest that RNI and FFA rather than ROI are important effectors of anti-MAC functions of mphis, and the collaborating action of RNI with FFA temporarily participates in mphi-mediated killing of MAC in the relatively early phase after MAC stimulation.
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PMID:Effector molecules in expression of the antimicrobial activity of macrophages against Mycobacterium avium complex: roles of reactive nitrogen intermediates, reactive oxygen intermediates, and free fatty acids. 940 Aug 21

Oxidative stress is well recognized to be a key step in the pathogenesis of ethanol-associated liver injury. Ethanol administration induces an increase in lipid peroxidation either by enhancing the production of oxygen reactive species and/or by decreasing the level of endogenous antioxidants. Numerous experimental studies have emphasized the role of the ethanol-inducible cytochrome P450 in the microsomes and the molybdo-flavoenzyme xanthine oxidase in the cytosol. This review shows the putative role of ethanol-induced disturbances in iron metabolism in relation to iron as a pro-oxidant factor. Ethanol administration also affects the mitochondrial free radical generation. Many previous studies suggest a role for active oxygens in ethanol-induced mitochondrial dysfunction in hepatocytes. Recent studies in our laboratory in the Department of Internal Medicine, Keio University, using a confocal laser scanning microscopic system strongly suggest that active oxidants generated during ethanol metabolism produce mitochondrial membrane permeability transition in isolated and cultured hepatocytes. In addition, acetaldehyde, ethanol consumption-associated endotoxaemia and subsequent release of inflammatory mediators may cause hepatocyte injury via both oxyradical-dependent and -independent mechanisms. These cytotoxic processes may lead to lethal hepatocyte injury. Investigations further implicate the endogenous glutathione-glutathione peroxidase system and catalase as important antioxidants and cytoprotective machinery in the hepatocytes exposed to ethanol.
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PMID:Pathogenesis of alcoholic liver disease with particular emphasis on oxidative stress. 940 47

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

Incubation of human or sheep platelet crude membranes with xanthine oxidase/hypoxanthine in the presence of Fe2+/ADP inactivated phosphotyrosine phosphatase (PTPase, protein-tyrosine-phosphate-phosphohydrolase, EC 3.1.3.48) activity in a time-dependent manner, this inhibition being significant within 5 min of treatment. The dynamics of protein thiols differed depending on the platelet species, but in any case decreases in protein thiols were only visible 20-45 min after the start of the treatment. The inhibition of PTPase activity in general showed good a correlation with the production of thiobarbituric acid-reactive substances (TBARS). The results with several antioxidants suggest that the inhibition of PTPase activity is related to the generation of alkoxyl and/or peroxyl radicals. Furthermore, the formation of fluorescent products and changes in amino groups were observed only after long incubation times with the oxidizing agents, these fluorescent products and the residual enzyme activity remaining in the membrane fraction. Treatment of platelet membranes with trans-2-nonenal and n-heptaldehyde, but not with acetaldehyde, also inhibited membrane-associated PTPase activity. However, the amount of protein thiols was reduced only by treatment with trans-2-nonenal. Fluorescence product formation was always higher with trans-2-nonenal, these products being mainly located in the protein fraction. The results with aldehydes suggest that secondary degraded products of lipid hydroperoxides affect PTPase activity. Kinetic studies of PTPase activity indicated that with all treatments enzyme inhibition is mainly due to a decrease in the Vmax value. The results of fluorescence anisotropy measurements of labeled platelet membranes did not support the notion of a contribution of the lipid organization to peroxidation-mediated PTPase inhibition. All the above results indicate that platelet membrane-associated PTPase inhibition due to treatment with xanthine oxidase/ hypoxanthine in the presence of Fe2+/ADP is a very complex, time-dependent process, and that it is probably related, at least after long periods of peroxidation, to changes in protein thiols and amino groups. We predict that the sensitivity of PTPase to lipid peroxidation must be physiologically relevant because of the increasing importance of tyrosine phosphorylation in signal transduction, in general, and in platelet activation and aggregation in particular.
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PMID:Oxidative inactivation of human and sheep platelet membrane-associated phosphotyrosine phosphatase activity. 1038 Nov 93


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