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)

Bovine milk xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2) has been purified by a modified method without the use of proteases, and its structure has been analyzed by polyacrylamide gel electrophoresis. Native xanthine oxidase is found to consist of only two polypeptide chains A with molecular weights of 150 000 each. These chains have NH2-terminal methionine. Limited proteolysis with trypsin, chymotrypsin, or subtilisin at pH 8 did not affect molecular weight and activities of the enzyme while each of the A chains was cleaved under these conditions to three fragments C, E, and F with molecular weights of 92 00, 42 000 and 20 000, respectively. These fragments remained bound to each other and were relatively resistant to subsequent proteolysis. The isolation of xanthine oxidase in the presence of pancreatin as described by Hart et al. (1970, Biochem. J. 116, 851) gives partially digested enzyme composed mainly of chains C, E (Mr 35 000) and a small component (Mr approx. 15 0-0). The action of subtilisin on xanthine oxidase at pH 11 resulted in complete digestion of E chains, FAD separation, and total loss of xanthine:oxygen oxidoreductase activity while xanthine:indophenol oxidoreductase activity was relatively little affected. The residual enzyme has a molecular weight of about 200 000, is composed mainly of two C chains (and may probably contain F and/or proteolytic fragments of low molecular weight), contains molybdenum, and does not contain FAD.
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PMID:Subunit structure of bovine milk xanthine oxidase. Effect of limited cleavage by proteolytic enzymes on activity and structure. 126 10

In vivo most extracellular iron is bound to transferrin or lactoferrin in such a way as to be unable to catalyze the formation of hydroxyl radical from superoxide (.O2-) and hydrogen peroxide (H2O2). At sites of Pseudomonas aeruginosa infection bacterial and neutrophil products could possibly modify transferrin and/or lactoferrin forming catalytic iron complexes. To examine this possibility, diferrictransferrin and diferriclactoferrin which had been incubated with pseudomonas elastase, pseudomonas alkaline protease, human neutrophil elastase, trypsin, or the myeloperoxidase product HOCl were added to a hypoxanthine/xanthine oxidase .O2-/H2O2 generating system. Hydroxyl radical formation was only detected with pseudomonas elastase treated diferrictransferrin and, to a much lesser extent, diferriclactoferrin. This effect was enhanced by the combination of pseudomonas elastase with other proteases, most prominently neutrophil elastase. Addition of pseudomonas elastase-treated diferrictransferrin to stimulated neutrophils also resulted in hydroxyl radical generation. Incubation of pseudomonas elastase with transferrin which had been selectively iron loaded at either the NH2- or COOH-terminal binding site yielded iron chelates with similar efficacy for hydroxyl radical catalysis. Pseudomonas elastase and HOCl treatment also decreased the ability of apotransferrin to inhibit hydroxyl radical formation by a Fe-NTA supplemented hypoxanthine/xanthine oxidase system. However, apotransferrin could be protected from the effects of HOCl if bicarbonate anion was present during the incubation. Apolactoferrin inhibition of hydroxyl radical generation was unaffected by any of the four proteases or HOCl. Alteration of transferrin by enzymes and oxidants present at sites of pseudomonas and other bacterial infections may increase the potential for local hydroxyl radical generation thereby contributing to tissue injury.
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PMID:Pseudomonas and neutrophil products modify transferrin and lactoferrin to create conditions that favor hydroxyl radical formation. 165 25

The xanthine oxidase reaction causes a co-oxidation of NH3 to NO2-, which was inhibitable by superoxide dismutase, catalase, hydroxyl radical scavengers, or by the chelating agents, desferrioxamine or diethylene triaminepentaacetic acid. Hydroxylamine was oxidized to NO2- much more rapidly than was NH3, and in this case superoxide dismutase or the chelating agents inhibited but catalase or the HO. scavengers did not. Hydrazine was not detectably oxidized to NO2-, and NO2- was not oxidized to NO3-, by the xanthine oxidase reaction. These results are accommodated by a reaction scheme involving (a) the metal-catalyzed production of HO. from O2- + H2O2; (b) the oxidation of H3N to H2N. by OH.; (c) the coupling of H2N. with O2- to yield peroxylamine, which hydrolyzes to hydroxylamine plus H2O2; (d) the metal-catalyzed oxidation of HO-NH2 to (Formula: see text), which couples with O2- to yield (Formula: see text), which finally dehydrates to yield NO2-.
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PMID:The co-oxidation of ammonia to nitrite during the aerobic xanthine oxidase reaction. 383 96

The oxidation of NH3 to NO3- by rat liver in vitro is described. A xanthine-xanthine oxidase reaction also oxidized NH3 to NO3- when H2O2 was added. An in vivo inhibitor of superoxide dismutase enhanced the in vitro liver conversion of NH3 to NO3-. Thus, intracellular oxidation by activated oxygen likely represents the source of endogenously formed NO3- in mammals.
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PMID:Activated oxygen and mammalian nitrate biosynthesis. 608 4

In response to a recent report (Lewis, A.S., Murphy, L., Mcalla, C., Fleary, M., and Purcell, S. (1984) J. Biol. Chem. 259, 12-15) that folic acid was a potent inactivator of xanthine oxidase, the details of this apparent inactivation were studied. In confirmation, we also found that commercially available folic acid produced a time-dependent progressive inhibition (apparent inactivation) of xanthine oxidase. A plot of the pseudo-first order rate constant of the decay of enzyme activity versus the concentration of folic acid resulted in a straight line. This indicated that the progressive inhibition was caused by a slow second order combination of an inhibitor with the enzyme. The second order rate constant for this association (slope of replot) was 5.7 X 10(3) M-1 S-1. The slowness of this constant together with the observation that complete inactivation did not occur suggested that the progressive inhibition might be due to the slow binding of a high affinity contaminant. This was corroborated by the finding that the association constant was decreased to 1.6 X 10(2) M-1 S-1 after partially purifying the folic acid. The compound most likely to be producing this inhibition is pterin aldehyde (2-NH2-4-OH-pteridine-6-aldehyde), a photolytic breakdown product of folic acid. Pterin aldehyde was found to be a progressive inhibitor of xanthine oxidase with an association constant of 2.2 X 10(5) M-1 S-1. When the apparent association constants of commercial and purified folic acid were adjusted to reflect the pterin aldehyde content (3.6% and 0.2%, respectively), they became similar to the association constant of pterin aldehyde. Thus, it seems that the apparent inactivation of xanthine oxidase by folic acid was caused by the slow binding of contaminating pterin aldehyde.
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PMID:Folic acid does not inactivate xanthine oxidase. 654 55

2,4-Dinitrotoluene (2,4-DNT) is an important industrial nitroaromatic compound. 2,4-Diaminotoluene (2,4-DAT), one of the urinary metabolites of 2,4-DNT, is carcinogenic when fed to rats. The objectives of these studies were to determine whether 2,4-DAT was formed from 2,4-DNT in rat liver and to clarify the nature of enzymes responsible for reduction of 2,4-DNT to 2,4-DAT. Data obtained from thin-layer and high-pressure liquid chromatography indicated that metabolites produced by microsomal preparations were 2-amino-4-nitrotoluene (2A4NT) and its isomer (4A2NT). This microsomal activity is probably mediated by cytochrome P-450 because the reduction is blocked by carbon monoxide and primary amines [aniline, n-octylamine, and 2,4-dichloro-6-phenylphenoxyethylamine (DPEA)]. In contrast, 2,4-DNT was metabolized via 2A4NT and 4A2NT to 2,4-DAT by cytosolic preparations. The greatest part of the reduction activity was due to cytosolic xanthine oxidase because the reduction was blocked by allopurinol. The results of this investigation suggest that reduction of 2,4-DNT to 2,4-DAT by cytosolic xanthine oxidase may play a role in 2,4-DNT hepatocarcinogenicity.
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PMID:Reduction of 2,4-dinitrotoluene by Wistar rat liver microsomal and cytosol fractions. 654 24

We have developed a unique rat AGML model produced by ischemia/reperfusion plus 0.2% ammonia (I/R.NH3), either treatment which would not induce mucosal injury when used alone. The effects of troxipide and other gastric mucosal defensive drugs were investigated with this I/R.NH3-induced AGML model and other AGML models in rats. The following results were obtained: 1) Like allopurinol, troxipide at 50-200 mg/kg, p.o. dose-dependently prevented I/R.NH3-induced development of AGML and also the ischemia/reperfusion-induced increase of gastric mucosal thiobarbituric acid (TBA)-reactive substances; 2) Troxipide at 10(-6)-10(-4) M, like allopurinol, inhibited concentration-dependently in vitro xanthine oxidase activity in gastric mucosal homogenates; 3) Troxipide at 50-200 mg/kg, p.o. inhibited AGMLs induced by bleeding plus 0.2% ammonia and by 1.0% ammonia alone; and 4) Troxipide and sofalcone were similar in preventing all AGMLs tested and also the increase of mucosal TBA-reactive substances, but somewhat differed from teprenone, cetraxate hydrochloride, azulene plus L-glutamine and sucralfate. These findings suggest that troxipide may inhibit I/R.NH3-induced AGML development by preventing generation of oxygen free radicals and by protecting against mucosal fragility due to reduced energy metabolism from poor blood flow and also against ammonia-induced disruption of the gastric mucosal barrier. Therefore, troxipide may be highly effective for various AGMLs with multifactor involvement.
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PMID:[Preventive effects of troxipide on a newly developed model of acute gastric mucosal lesion (AGML) induced by ischemia/reperfusion plus ammonia in the rat]. 795 22

The potential of xanthine oxidoreductase to generate oxygen radicals depends on the ratio of xanthine dehydrogenase and xanthine oxidase. Previous studies showed that the lipid peroxidation products, malondialdehyde and 4-hydroxynonenal have different effects on xanthine oxidoreductase activity. These results suggest that the activity of xanthine oxidase, but not xanthine dehydrogenase, is influenced by NH2-group modulation. We therefore investigated the influence of malondialdehyde on xanthine oxidoreductase. Malondialdehyde reacted with NH2-groups to form Schiff bases, and this reaction was associated with inhibition of xanthine oxidase; SH-groups were not affected. Malondialdehyde had no influence on the xanthine dehydrogenase activity. The inhibited xanthine oxidase was converted to an active xanthine dehydrogenase by dithiothreitol treatment. These experiments indicate the importance of NH2-groups for xanthine oxidase but not for xanthine dehydrogenase activity. Beside the well known regulation of the xanthine dehydrogenase/xanthine oxidase ratio by the redox status of SH-groups, substances reacting with NH2-groups of the xanthine oxidoreductase are also able to change the xanthine dehydrogenase/xanthine oxidase activity ratio, thereby influencing the potential to generate oxygen radicals by xanthine oxidoreductase.
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PMID:Modulation of the xanthine oxidase/xanthine dehydrogenase ratio by reaction of malondialdehyde with NH2-groups. 803 67

A new kinetic method for the determination of serum adenosine deaminase (EC 3.5.4.4) is described, with adenosine as the substrate and nucleoside phosphorylase and xanthine oxidase as the reaction enzymes. Inosine is produced, which is converted to hypoxanthine. The hypoxanthine is oxidized to xanthine, which is further oxidized to uric acid. In these two reactions, blue 2,6-dichlorophenolindophenol is reduced to a colorless compound and the decrease in color is measured spectrophotometrically at 606 nm. The assay was automated by using a Cobas Mira analyzer. The automated assay had a CV of < 7%, and the calibration curve was linear from 10 to 120 U/L. The assay correlates well with an established method, based on detection of liberated NH3 with Berthelot's reaction. The reference interval (mean +/- 2 SD) was 14-34 U/L (mean 24 U/L, n = 84). The enzymatic method described is easily automated and seems to be suitable for the routine determination of adenosine deaminase in serum.
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PMID:Kinetic determination of serum adenosine deaminase. 840 5

Modifications in lens protein structure and function due to nonenzymic glycosylation and oxidation have been suggested to play a significant role in the pathogenesis of sugar and senile cataracts. The glycation reaction involves an initial Schiff base formation between the protein NH2 groups and the carbonyl group of a reducing sugar. The Schiff base then undergoes several structural modifications, via some oxidative reactions involving oxygen free radicals. Hence certain endogenous tissue components that may inhibit the formation of protein-sugar adduct formation may have a sparing effect against the cataractogenic effects of sugars and reactive oxygen. The eye lens is endowed with significant concentration of taurine, a sulfonated amino acid, and its precursor hypotaurine. It is hypothesized that taurine and hypotaurine may have this purported function of protecting the lens proteins against glycation and subsequent denaturation, in addition to their other functions. The results presented herein suggest that these compounds are indeed capable of protecting glycation competitively by forming Schiff bases with sugar carbonyls, and thereby preventing the glycation of lens proteins per se. In addition, they appear to prevent oxidative damage by scavenging hydroxyl radicals. This was apparent by their preventive effect against the formation of the thiobarbituric acid reactive material generated from deoxy-ribose, when the later was exposed to hydroxyl radicals generated by the action of xanthine oxidase on hypoxanthine in presence of iron.
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PMID:Prevention of lens protein glycation by taurine. 945 Jun 69


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