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)

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

Bacterial translocation (BT) occurs transiently after thermal injury and may result from an ischemic intestinal insult. To evaluate continued intestinal ischemia in the ongoing BT associated with sepsis after injury, rats were randomized to (1) 30% burn injury with Pseudomonas wound infection (BI), (2) BI + fluid resuscitation (BI + Fluid), (3) BI after allopurinol pretreatment to inhibit xanthine oxidase (BI + Allo), or (4) BI after azapropazone pretreatment to inhibit neutrophil degranulation (BI + Aza). On postburn days (PBD) 1, 4, and 7, animals were studied for evidence of BT and intestinal lipid peroxidation. BI + Fluid, BI + Allo, and BI + Aza significantly (p less than 0.05) reduced rates of BT and ileal lipid peroxidation acutely after thermal injury (PBD 1) compared to BI. All four groups had equally high rates of BT associated with the onset of sepsis (PBDs 4 and 7), without evidence of further intestinal lipid peroxidation. These data indicate that the chronic gut barrier failure associated with sepsis after injury occurs independently of continued intestinal ischemia.
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PMID:Differential pathophysiology of bacterial translocation after thermal injury and sepsis. 206 68

Josamycin and erythromycin have been compared for their in-vitro interaction with bactericidal killing by human neutrophils. The mechanism of this interaction was studied in two ways. First, the target organisms (Staphylococcus aureus and Pseudomonas aeruginosa) were incubated for 60 min with josamycin, erythromycin or control buffer prior to use in a human polymorphonuclear neutrophil (PMN) killing assay. Second the macrolides were added directly to acellular killing systems mimicking those acting inside the phagolysosome; oxygen-independent systems were obtained from a crude granule extract of PMN and oxygen-dependent systems consisted either of a mixture of xanthine plus xanthine oxidase or of a solution of H2O2. Whereas josamycin-pretreated P. aeruginosa were twice as sensitive to killing by PMN than were control cells, this was not the case for S. aureus. Both oxidant generating systems were more effective in destroying S. aureus in the presence of josamycin (3 and 30 mg/l). Erythromycin showed a similar synergy but only with the xanthine plus xanthine oxidase system. This synergy was observed with neither of the O2-independent systems for S. aureus, nor with any acellular system for P. aeruginosa. These data suggest that at least two kinds of mechanism may explain the bactericidal synergy observed between macrolides and PMN. The first (for macrolide-resistant species such as P. aeruginosa) could be due to alterations in the bacteria by the antibiotics, while the second (for macrolide-sensitive species such as S. aureus) could be based upon an as yet unexplained transformation of the molecules by reactive oxygen species into more "toxic" forms. These differences between josamycin and erythromycin could arise from differences in their chemical structure.
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PMID:Synergistic bactericidal interaction of josamycin with human neutrophils in vitro. 212 51

Tissue injury has been linked to neutrophil associated hydroxyl radical (.OH) generation, a process that requires an exogenous transition metal catalyst such as iron. In vivo most iron is bound in a noncatalytic form. To obtain iron required for growth, many bacteria secrete iron chelators (siderophores). Since Pseudomonas aeruginosa infections are associated with considerable tissue destruction, we examined whether iron bound to the Pseudomonas siderophores pyochelin (PCH) and pyoverdin (PVD) could act as .OH catalysts. Purified PCH and PVD were iron loaded (Fe-PCH, Fe-PVD) and added to a hypoxanthine/xanthine oxidase superoxide- (.O2-) and hydrogen peroxide (H2O2)-generating system. Evidence for .OH generation was then sought using two different spin-trapping agents (5.5 dimethyl-pyrroline-1-oxide or N-t-butyl-alpha-phenylnitrone), as well as the deoxyribose oxidation assay. Regardless of methodology, .OH generation was detected in the presence of Fe-PCH but not Fe-PVD. Inhibition of the process by catalase and/or SOD suggested .OH formation with Fe-PCH occurred via the Haber-Weiss reaction. Similar results were obtained when stimulated neutrophils were used as the source of .O2- and H2O2. Addition of Fe-PCH but not Fe-PVD to stimulated neutrophils yielded .OH as detected by the above assay systems. Since PCH and PVD bind ferric (Fe3+) but not ferrous (Fe2+) iron, .OH catalysis with Fe-PCH would likely involve .O2(-)-mediated reduction of Fe3+ to Fe2+ with subsequent release of "free" Fe2+. This was confirmed by measuring formation of the Fe2(+)-ferrozine complex after exposure of Fe-PCH, but not Fe-PVD, to enzymatically generated .O2-. These data show that Fe-PCH, but not Fe-PVD, is capable of catalyzing generation of .OH. Such a process could represent as yet another mechanism of tissue injury at sites of infection with P. aeruginosa.
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PMID:Possible role of bacterial siderophores in inflammation. Iron bound to the Pseudomonas siderophore pyochelin can function as a hydroxyl radical catalyst. 217 Apr 42

3 alpha-Hydroxysteroid dehydrogenase (EC 1.1.1.50) from Pseudomonas testosterone was inactivated by superoxide radicals generated by the aerobic xanthine oxidase reaction. Superoxide dismutase, NAD+, bovine serum albumin and histidine and cysteine as free amino acids partially protected the enzyme from inactivation. NADH-binding properties were determined by fluorescence spectroscopy, and no variation was found between native enzyme and the unmodified fraction of the partly inactivated one. The fluorescence emission maximum for the completely inactivated enzyme was shifted 10 nm to a longer wavelength when compared with the native one, and it seems possible that the modification of histidine and cysteine residues by superoxide radicals causes the conformational change of the enzyme and the consequent loss of catalytic activity.
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PMID:Inactivation of 3 alpha-hydroxysteroid dehydrogenase by superoxide radicals. Modification of histidine and cysteine residues causes the conformational change. 300 70

Liver xanthine oxidase (XOD) and superoxide dismutase (SOD) activities were compared in mice during Salmonella typhimurium and Pseudomonas aeruginosa infections. We observed that XOD activity rose but SOD activity fell for the first 11 days after infection with smooth type S. typhimurium, coinciding with the period of bacterial growth in the liver. Rough type S. typhimurium did not establish an infection and mice inoculated with this strain showed no variation in enzyme activities. P. aeruginosa infection was mild but stimulated both XOD and SOD activities.
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PMID:Changes in hepatic superoxide dismutase and xanthine oxidase activity in mice infected with Salmonella typhimurium and Pseudomonas aeruginosa. 313 9

For the three Gram-negative bacteria, Pseudomonas fluorescens, Escherichia coli, and Erwinia amylovora, p-benzoquinone was the principal bactericidal agent formed in vitro during the oxidation of hydroquinone by horseradish peroxidase, whereas no toxicity could be associated with either phenolic or oxygen-free radicals. Even the continuous generation of p-benzosemiquinone during the simultaneous reduction of p-benzoquinone by xanthine oxidase and reoxidation of hydroquinone by peroxidase was no more toxic than p-benzoquinone alone. Anaerobiosis had no effect on the toxicity of either p-benzoquinone or the peroxidase reaction and the generation of superoxide and hydroxyl radicals catalyzed by xanthine oxidase was not bactericidal. Substitutions on the p-benzoquinone ring decreased quinone toxicity in rough proportion to the decrease in quinone redox potential, suggesting that strong oxidizing potentials are important for such quinone toxicity.
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PMID:Bactericidal agents generated by the peroxidase-catalyzed oxidation of para-hydroquinones. 393 58

Cell-free particles from Pseudomonas rubescens have been shown to reduce hydroxocobalamin to vitamin B(12r). The particles are unable to reduce the B(12r) to B(12s). The reduction of hydroxocobalamin is dependent upon reduced nicotinamide adenine dinucleotide and is stimulated by flavin adenine dinucleotide. Cobinamide and diaquocobinamide were reduced at 25 and 10%, respectively, of the rate of hydroxocobalamin. Cyanocobalamin, coenzyme B(12), pseudovitamin B(12), and diaquopseudocobalamin were not reduced. Reduced nicotinamide adenine dinucleotide phosphate and flavin mononucleotide were not active. Diaphorase and xanthine oxidase activity were not present in the particulate fraction.
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PMID:Microbial degradation of corrinoids. VI. Reduction of hydroxocobalamin by cell-free particles from Pseudomonas rubescens. 438 87

Carbon monoxide:methylene blue oxidoreductase, the key enzyme of CO-oxidation in energy metabolism of the carboxydobacterium Pseudomonas carboxydovorans, has been isolated in good yield and purity and found to contain FAD, molybdenum, iron, and labile sulfide in the ratio of 1:1:4:4. The enzyme is, therefore, a new molybdenum-containing iron-sulfur flavoprotein, exhibiting chemical and spectral properties quite similar to those of xanthine oxidase. Analytical data on the spectral characteristics of the enzyme in the oxidized and various reduced states are presented. Carbon monoxide:methylene blue oxidoreductase turned out to be photoreducible in the presence of EDTA and urea and was subject to reoxidation by air oxygen; no flavoprotein semiquinone was formed. Unphysiological electron acceptors, e.g. methylene blue, were used as oxidizing substrates whereas NAD or NADP turned out to be ineffective. Methylene blue reduction with CO was not affected by the presence of allopurinol, and carbon monoxide:methylene blue oxidoreductase was not able to catalyze the reduction of methylene blue with xanthine, adenine, or aldehydes. CO was the only reducing substrate used by the enzyme. Carbon monoxide:methylene blue oxidoreductase formed no sulfite adduct, and the reactivity with ferricyanide or cytochrome c was significant but slow. As known for other molybdenum hydroxylases, carbon monoxide:methylene blue oxidoreductase was rapidly inactivated by methanol, but the enzyme exhibited no ability to catalyze the oxidation of NADH with methylene blue, and NAD was not able to overcome methanol inhibition.
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PMID:Chemical and spectral properties of carbon monoxide: methylene blue oxidoreductase. The molybdenum-containing iron-sulfur flavoprotein from Pseudomonas carboxydovorans. 627 81

E.p.r. spectra were obtained at 8-120 K for carbon monoxide oxidases isolated from the carboxydotrophic bacteria Pseudomonas carboxydovorans and Pseudomonas carboxydohydrogena. Spectra from the two enzymes are extremely similar to one another. Under appropriate conditions each enzyme shows signals from Mo(V) atoms in two different chemical environments, as well as showing signals from two distinct iron-sulphur centres, presumed to be [2Fe-2S] clusters, and weak FADH X free-radical signals. Parameters of most of the signals were measured, and they show considerable similarities to those of the corresponding signals from xanthine oxidase and related enzymes. Though the signals from carbon monoxide oxidases appear and disappear under reducing and oxidizing conditions, we have so far failed to demonstrate the kinetic competence of any of them. It seems likely that this was due to the presence in the enzyme preparation examined of high amounts of desulpho carbon monoxide oxidase together with another non-functional form of the enzyme giving a stable 'Resting' Mo(V) e.p.r. signal.
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PMID:Studies by e.p.r. spectroscopy of carbon monoxide oxidases from Pseudomonas carboxydovorans and Pseudomonas carboxydohydrogena. 630 36


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