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)

Senescent cell antigen (SCANT) is a "neo antigen" that appears on the surface of normal old cells and initiates IgG binding and cellular removal. To investigate the mechanism by which SCANT is generated from its parent molecule, band 3, we subjected intact human erythrocytes to treatments that have been reported to result in changes in band 3 and/or to mimick aging in vitro. The validity of these treatments as model systems for erythrocyte aging was evaluated using a "red cell aging panel" that provides a biochemical profile of a senescent red cell. Treatments were assessed for their ability to induce in vitro the following changes observed in normal erythrocytes aged in vivo: 1 increased breakdown of band 3 as detected by immunoblotting, 2 decrease in anion transport efficiency as detected with a sulfate self-exchange assay, 3 decrease in total glyceraldehyde 3-phosphate dehydrogenase activity with an increase in membrane-bound activity, and 4 increase in the binding of autologous IgG as detected with a protein A binding assay. Neither incubation with the free radical-generating xanthine oxidase/xanthine system, nor treatment with malondialdehyde, and end product of free radical-initiated lipid (per)oxidation, results in age-specific changes. Loading of the cells with calcium and oxidation with iodate results in increased breakdown of band 3, but does not lead to increased binding of autologous IgG. Only erythrocytes that have been stored for 3-4 weeks show the same structural and functional changes as observed during aging in vivo.
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PMID:Erythrocyte aging: a comparison of model systems for simulating cellular aging in vitro. 317 56

The chain oxidation of glyceraldehyde-3-phosphate dehydrogenase.NADH by perhydroxyl radicals and propagated by molecular oxygen was studied by the xanthine-xanthine oxidase system, 60Co gamma-ray, and pulse radiolysis. The chain length, amount of NADH oxidized per HO2 generated, increases with increasing acidity of the medium and reaches a value of 73 at pH 5.0. The rate constant for the oxidation of the glyceraldehyde-3-phosphate dehydrogenase.NADH complex by HO2 was estimated to be 2 X 10(7) M-1 S-1 at ambient temperatures (23-24 degrees C). Rate studies as a function of pH indicate that O2- is unreactive toward the glyceraldehyde-3-phosphate dehydrogenase.NADH complex. Other dehydrogenases (malate dehydrogenase, glutamate dehydrogenase, and isocitric dehydrogenase) studied showed no catalytic activity in the oxidation of NADH by HO2/O2-.
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PMID:Glyceraldehyde-3-phosphate dehydrogenase-catalyzed chain oxidation of reduced nicotinamide adenine dinucleotide by perhydroxyl radicals. 718 97

The effects of a xanthine oxidase-mediated free radical-generating system containing purine and iron-loaded transferrin or solutions containing hydrogen peroxide and iron-loaded transferrin on substrate utilization and high-energy phosphates were evaluated by nuclear magnetic resonance (NMR) spectroscopy in isolated perfused rat hearts. Hearts were supplied with lactate, acetate, and glucose, and the contribution of each substrate to acetyl coenzyme A was measured in control hearts and in the presence of a free radical-generating system. Perfused hearts were monitored by 31P NMR, and tissue extracts were analyzed by 13C NMR. Free radicals decreased the phosphocreatine and beta-ATP peak areas and reduced contractile function. Under control conditions, lactate, acetate, and endogenous sources were the major contributors of acetyl coenzyme A units, with only 5% originating from glucose. In the presence of a xanthine oxidase-mediated free radical-generating system, the glucose contribution increased to 54%, while contributions from acetate and endogenous sources were significantly reduced. Both 13C and 31P NMR analyses showed no significant accumulation of glycolytic sugar phosphates, suggesting little inhibition of glyceraldehyde-3-phosphate dehydrogenase. The increased contribution of glucose to the tricarboxylic acid cycle relative to acetate and endogenous sources is consistent with activation of pyruvate dehydrogenase. In contrast, hearts exposed to a hydrogen peroxide-based free radical-generating system showed an increase in lactate utilization, a decrease in acetate utilization, and no change in glucose utilization compared with control hearts. Glycolytic sugar phosphates were found to accumulate, suggesting possible inhibition of glyceraldehyde-3-phosphate. Thus, different radicals or their metabolites may have varying effects on myocardial metabolism.
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PMID:Effects of oxidant exposure on substrate utilization and high-energy phosphates in isolated rat hearts. 791 69

Exposure of bovine aortic endothelial cells in vitro to oxidative stress causes a cascade of changes in cell function, culminating in cell death if the stress is sufficiently severe. Oxidative modification of proteins, as measured by the reaction of 2,4-dinitrophenylhydrazine with carbonyl groups of oxidized proteins, increased three- to fourfold in endothelial cells exposed to hydrogen peroxide or to a xanthine/xanthine oxidase system. The increase in oxidative modification of protein occurred rapidly, preceding loss of cellular ATP and eventual cell death. Oxidative modification of protein was paralleled by loss of activity of the key metabolic enzymes, glucose-6-phosphate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The finding that oxidative modification of protein is an early event following oxidative stress suggests that oxidative modification of protein is not only a marker for oxidative damage but also a causal factor in oxidative injury.
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PMID:Modification of proteins in endothelial cell death during oxidative stress. 909 2

Among progeny of a hybrid (Rana shqiperica x R. lessonae) x R. lessonae, 14 of 22 loci form four linkage groups (LGs): (1) mitochondrial aspartate aminotransferase, carbonate dehydratase-2, esterase 4, peptidase D; (2) mannosephosphate isomerase, lactate dehydrogenase-B, sex, hexokinase-1, peptidase B; (3) albumin, fructose-biphosphatase-1, guanine deaminase; (4) mitochondrial superoxide dismutase, cytosolic malic enzyme, xanthine oxidase. Fructose-biphosphate aldolase-2 and cytosolic aspartate aminotransferase possibly form a fifth LG. Mitochondrial aconitate hydratase, alpha-glucosidase, glyceraldehyde-3-phosphate dehydrogenase, phosphogluconate dehydrogenase, and phosphoglucomutase-2 are unlinked to other loci. All testable linkages (among eight loci of LGs 1, 2, 3, and 4) are shared with eastern palearctic water frogs. Including published data, 44 protein loci can be assigned to 10 of the 13 chromosomes in Holarctic Rana. Of testable pairs among 18 protein loci, agreement between Palearctic and Nearctic Rana is complete (125 unlinked, 14 linked pairs among 14 loci of five syntenies), and Holarctic Rana and Xenopus laevis are highly concordant (125 shared nonlinkages, 13 shared linkages, three differences). Several Rana syntenies occur in mammals and fish. Many syntenies apparently have persisted for 60-140 x 10(6) years (frogs), some even for 350-400 x 10(6) years (mammals and teleosts).
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PMID:Linkage groups of protein-coding genes in western palearctic water frogs reveal extensive evolutionary conservation. 928 85

We examined if paraquat-induced oxidative stress and cytotoxicity in pulmonary microvascular endothelial cells are associated with cellular redox systems such as the glutathione system and the thioredoxin system. Loss of viability, accompanied by marked decreases in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and thioredoxin reductase activities, occurred 48 h after exposure to 1mM paraquat. These changes were preceded by an increased production of hydrogen peroxide after the decrease in glutathione peroxidase activity. Glutaredoxin activity was not decreased even after exposure to paraquat for 48 h, whereas thioredoxin activity was slightly decreased at 48 h. Unexpectedly, the activity of peroxiredoxin, a non-selenoenzyme, was almost completely lost at 24h. Loss of GAPDH activity and viability was notably aggravated by mercaptosuccinate. Selenium supplementation suppressed the loss of activities of glutathione peroxidase and thioredoxin reductase and alleviated paraquat-induced cytotoxicity. An in vitro experiment demonstrated that GAPDH was highly susceptible to reactive oxygen species generated in the xanthine-xanthine oxidase system, whereas thioredoxin reductase was considerably resistant. Taken together, the results suggest that the reduced regenerative ability of oxidatively damaged proteins including GAPDH due to the inactivation of thioredoxin reductase and glutathione peroxidase by paraquat may contribute to increasing oxidative stress, leading to cell death.
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PMID:Paraquat-induced oxidative stress and dysfunction of cellular redox systems including antioxidative defense enzymes glutathione peroxidase and thioredoxin reductase. 1705 14

Anti- and prooxidant properties of quercetin under different conditions were investigated using glyceraldehyde-3-phosphate dehydrogenase, a glycolytic enzyme containing essential cysteine residues. Quercetin was shown to produce hydrogen peroxide in aqueous solutions at pH 7.5, this resulting in the oxidation of the cysteine residues of the enzyme. Quercetin significantly increased oxidation of GAPDH observed in the presence of ferrous ions, particularly when FeSO(4) was added to the solution containing GAPDH and quercetin. The results suggest the formation of hydroxyl radical in the case of the addition of FeSO(4) to a quercetin solution. At the same time, quercetin protects GAPDH from oxidation in the presence of ascorbate and Fe(3+). In the absence of metals, quercetin protects SH-groups of GAPDH from oxidation by the superoxide anion generated by the system containing xanthine/xanthine oxidase.
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PMID:Antioxidant and prooxidant effects of quercetin on glyceraldehyde-3-phosphate dehydrogenase. 1755 99

The reduction of acetaldehyde back to ethanol via NAD-linked alcohol dehydrogenase is an important mechanism for keeping acetaldehyde levels low following ethanol ingestion. However, this does not remove acetaldehyde from the body, but just delays its eventual removal. Acetaldehyde is removed from the body primarily by oxidation to acetate via a number of NAD-linked aldehyde dehydrogenase (ALDH) enzymes. There are nineteen known ALDHs in humans, but only a few of them appear to be involved in acetaldehyde oxidation. There are many analogous enzymes in other organisms. Genetic polymorphisms of several ALDHs have been identified in humans that are responsible for several hereditary defects in the metabolism of normal endogenous substrates. The best known ALDH genetic polymorphism is in ALDH2 gene, which encodes a mitochondrial enzyme primarily responsible for the oxidation of the ethanol-derived acetaldehyde. This common polymorphism is known to dominantly inhibit its enzymatic activity resulting in reduced ability to clear acetaldehyde in both homozygote and heterozygote individuals. These individuals are generally protected against alcohol abuse but are susceptible to oesophageal cancer. For those enzymes that are capable of reacting with acetaldehyde, they may do so at the expense of their normal substrates, resulting in abnormal accumulation of these substrates. Examples of this are the aldehydes of the biogenic amines, dopamine, noradrenaline, adrenaline, serotonin and long chain lipid aldehydes such as nonenal. Not all of these enzymes are capable of efficient oxidation of acetaldehyde; however, it is possible that acetaldehyde may function as an inhibitor of these enzymes as well. The aldehydes whose metabolism is interfered with may also serve as inhibitors of ALDHs as well. However, this aspect of aldehyde function has not been extensively studied. A number of other mechanisms for the removal of acetaldehyde exist. For example, reaction of acetaldehyde with protein or nucleic acids is responsible for the disappearance of a small amount of acetaldehyde, but may be responsible for some pathological effects of acetaldehyde. There are a few other enzymes such as aldehyde oxidase, xanthine oxidase, cytochrome P450 oxidase and glyceraldehyde-3-phosphate dehydrogenase that are capable of oxidizing acetaldehyde. However, these enzymes account for only a small fraction of the total activity.
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PMID:Removal of acetaldehyde from the body. 1759 Sep 85

The modification of 5-hydroxyindoleacetic acid (5HIAA) by myeloperoxidase with a xanthine oxidase system was investigated by chromatographic analyses. Two major products were identified as a dimer and quinone (indoleacetate dione) of 5HIAA. The formation of a quinone moiety was also confirmed by chemical trapping with o-phenylenediamine. In the presence of N-acetyl-cysteine (NAC), a quinone-NAC adduct was formed. When glyceraldehyde 3-phosphate dehydrogenase was exposed to the myeloperoxidase system with 5HIAA, quinone adducts were formed on the protein molecule. A monoclonal antibody was prepared using a quinone-modified protein as an immunogen to immunochemically detect the quinone on a protein. The established antibody recognized the quinone-NAC adduct, quinone-modified poly-L-lysine, and quinone-modified low-density lipoprotein. Quinone-modified proteins in human atherosclerotic lesions were immunohistochemically observed using the established antibody to the quinone and also a monoclonal antibody to tryptamine dione-modified protein, suggesting an occurrence of in vivo oxidation of serotonin and 5HIAA, accompanied by covalent adduction to biomolecules.
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PMID:A novel quinone derived from 5-hydroxyindoleacetic acid reacts with protein: Possible participation of oxidation of serotonin and its metabolite in the development of atherosclerosis. 2785 48