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)

To investigate the mechanism of cardiac ischemia reperfusion injury, we fed rats tungsten (3 weeks) to inhibit molybdenum-dependent oxidase enzymes. Tungsten-treated isolated perfusion hearts (Langendorff, ventricular balloon, 37 degrees C) had negligible xanthine oxidase activity (less than 0.3 vs greater than 8.0 U/gm myocardium) and improved recovery of developed pressure (DP), contractility (+dP/dt), and compliance (-dP/dt) after 20 minutes of global ischemia (37 degrees C) and 40 minutes of reperfusion. Furthermore, the addition of dimethylthiourea, a freely diffusible O2 metabolite scavenger, but not equimolar urea, a non-O2 metabolite scavenger, improved recovery. High-dose urea improved recovery more than control but less than dimethylthiourea. Combining tungsten and equimolar urea improved recovery the same as dimethylthiourea. We conclude that: (1) inhibition of myocardial oxidase enzymes (including xanthine oxidase) improves recovery of ventricular function after ischemia and reperfusion in the isolated rat heart, (2) infusion (during reperfusion) of a permeable O2 metabolite scavenger (dimethylthiourea) but not equimolar urea improves recovery of ventricular function, (3) infusion of higher concentrations of urea improves postischemic function, and (4) myocardial reperfusion injury is distinguishable from ischemic injury.
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PMID:Cardiac oxidase systems mediate oxygen metabolite reperfusion injury. 313 26

Xanthine oxidase (EC 1.2.3.2) was purified from fresh cows' milk by differential centrifugation and hydroxylapatite chromatography in the absence of reducing agents and proteases. The purified isolate possessed an absorbance at 280 nm:absorbance at 450 nm ratio of 4.84; an absorbance (1 cm at 280 nm 1%) of 11.9; an activity:absorbance at 450 nm of 141, a specific activity of 3.59 units/mg; and detectable dehydrogenase activity. The enzyme preparation was obtained in a reversible oxidase form that could be partially converted to xanthine dehydrogenase in the presence of 10mM dithiothreitol or 1% mercaptoethanol. Amino acid analyses revealed that the enzyme was hydrophobic in nature and that lysine constituted its N-terminal residue. The protein contained 22 disulfide and 38 sulfhydryl groups, four of which were detectable in the undenatured protein complex. Discontinuous PAGE in the presence of selected dissociation agents did not result in further resolution. Sodium dodecyl sulfate-PAGE of the purified enzyme revealed a sharp zone with a molecular weight of 151,000 +/- 4000 (i.e., monomer). The purified enzyme exhibited oxidase activity in the presence of 6 M urea and following limited proteolysis by trypsin, chymotrypsin, plasmin, pancreatin, pepsin, and papain. Proteolyzed xanthine oxidase migrated as a single zone in polyacrylamide gels in the presence and absence of dissociating agents such as 1% mercaptoethanol and 6 M urea. Restricted digestion of xanthine oxidase by proteases was indicated by the presence of three major zones with molecular weights ranging from 85,000 to 100,000, 30,000 to 35,000, and 18,000 to 20,000 commonly observed in SDS gels. Amino acid profiles of the principal peptidyl fragments of trypsin-cleaved xanthine oxidase indicated their hydrophobic nature and lysine as the N-terminal residue for all fragments.
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PMID:Characteristics of purified cows' milk xanthine oxidase and its submolecular characteristics. 339 6

By using EPR spectroscopy of spin-labelled bovine serum albumin (BSA), bendazac was shown to prevent the BSA denaturation induced by urea, heat and free radicals produced in the xanthine/xanthine oxidase system. Bendazac did not inhibit the reduction of ferricytochrome c due to the superoxide flux in the above system nor did it possess a significant antioxidant activity on Fe(II) or Fe(III)-induced peroxidation of lecithin liposomes. It is concluded that the scavenger-like activity of bendazac is due to its interaction with protein molecules, rather than free radicals.
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PMID:Mechanism of the scavenger-like activity of bendazac. 367 37

Isolation-perfusion was used as a means of heating human livers with cancer. Perfusion was at 42-42.5 degrees C for 4 h. Perfusate constituents were analyzed in an attempt to identify factors contributing to the hepatotoxic effects of hyperthermia. During perfusion the perfusate constituents analyzed were: urea; total amino acids; uric acid; malonaldehyde; and lysosomal enzymes. Hepatic ammonia for urea synthesis is derived from degradation of amino acids, amines, and nucleic acids. An increase in proteolysis was reflected in the increase in urea from 0.6 +/- 0.2 mM to 1.9 +/- 8 mM and total amino acids from 1.0 +/- 0.6 mM to 4.4 +/- 1.7 mM during the 4 h of perfusion at 42-42.5 degrees C. An increase in purine catabolism occurred as evidenced by an increase in perfusate uric acid from 1.7 +/- 1.0 mg/100 ml to 6.1 +/- 2.7 mg/100 ml. Free oxygen radicals, which can lead to lipid peroxidation, are generated by the action of xanthine oxidase on xanthine. Lipid peroxidation occurring during perfusion was assessed by an increase in malonaldehyde from 2.3 +/- 1.3 microM to 10.4 +/- 10.0 microM. An increase in acid phosphatase in the perfusate from 38 +/- 15 units/liter to 78 +/- 45 units/liter occurred, suggesting labilization of lysosomes, perhaps through lipid peroxidation. Proteolysis and lipid peroxidation are suggested to be two interrelated factors contributing to heat toxicity in the perfused human liver with cancer.
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PMID:Nitrogen metabolism and lipid peroxidation during hyperthermic perfusion of human livers with cancer. 375 36

Inhibition of conversion from IMP to uric acid, which interferes with both spectrophotometric and radioisotopic assays of IMP dehydrogenase, by addition of allopurinol (0.1 mM), an inhibitor of xanthine oxidase, to the incubation system made it possible to determine the enzyme activity in crude liver extracts. With this improved assay method, the regulatory properties of the enzyme in crude extracts of liver and Yoshida sarcoma ascites cells were examined. In both tissues IMP dehydrogenase was found in the postmicrosomal supernatant. However, further centrifugation resulted in precipitation of the enzyme, the enzyme from Yoshida sarcoma ascites cells being precipitated more easily than that from rat liver. It was also found that IMP dehydrogenase activity increased during liver regeneration and that this increase was associated with the precipitate from the postmicrosomal fraction. These findings suggest that such a large sedimentable complex including IMP dehydrogenase might be formed in relation to cell growth. Most of the enzyme activity in rat liver and Yoshida sarcoma ascites cells was extracted in the supernatant obtained by centrifugation at 105,000 X g for 4 h after treatment of tissue homogenates with 1 M KCl, 0.75 M (NH4)2SO4, 2 M dimethylsulfoxide, 2 M KSCN, 25% glycerol, or 0.8 M guanidine-HCl. Treatment with 2% deoxycholate, 2% Triton X-100 or 2 M urea gave limited extraction. The enzyme was retained on a phenyl-Sepharose CL-6B or octyl-Sepharose CL-6B column and eluted with 0.8 M guanidine-HCl. These results suggested that the enzyme molecule has not only ionic but also hydrophobic domains, through which it interacts with other molecules of the enzyme itself and/or postmicrosomal cellular components.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:IMP dehydrogenase. I. Studies on regulatory properties of crude tissue extracts based on an improved assay method. 614 Feb 63

Vegetative and reproductive cells of Basidiobolus haptosporus possess naturally occurring organelles identified as microbodies. Cells of four other species of the genus contained morphologically indistinguishable organelles. Microbodies were invariably present in cells of the fungi grown on routine mycological media. The constitutive microbody was characterized by a single, intensely electron-opaque crystalloid body which rapidly enlarged to fill the organellar compartment. The microbody then underwent degeneration by an autolytic-like process. Growth of the fungi on xanthine and its catabolites as sole nitrogen sources (but not urea) greatly enhanced the production of new microbodies in which protein was initially accumulated as paracrystalline arrays. These inclusions then underwent reorganization and compaction to form crystalloid bodies. Key enzymes of the purine degradation pathway are believed to be core proteins of the crystalloid. D-amino acid oxidase, alpha-hydroxy acid oxidase, xanthine oxidase and urate oxidase (but not catalase) were detected cytochemically in mature microbodies. Significant levels of phosphorus and molybdenum were present in the microbody crystalloid by X-ray dispersive microanalysis; iron and copper were not detected. The ability of Basidiobolus species to assimilate xanthine and its catabolites might explain their ecological association with the gut and cloacal contents of various amphibia, reptiles and fish.
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PMID:Ultrastructural cytology of Basidiobolus haptosporus: morphology and electron cytochemistry of microbodies. 615 82

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

In a metabolic ward study of five patients, azapropazone lowered plasma uric acid but exerted only a modest and variable uricosuric effect without altering urinary xanthine and hypoxanthine levels. An alternative mechanism other than uricosuria or xanthine oxidase inhibition must account for some of the hypouricaemic action of this drug. During the first day of treatment urine volume and pH declined sharply. In a separate investigation, 22 patients were given azapropazone and 18 were given allopurinol combined with colchicine for 3 months. Allopurinol reduced plasma uric acid more quickly but at the end of the study there was little difference in the hypouricaemic results achieved by both drugs. Recurrent gout occurred more frequently with allopurinol but side-effects were confined to those taking azapropazone. A slight rise in blood urea and creatinine and a fall in haemoglobin were also features of long-term azapropazone treatment.
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PMID:Azapropazone--a treatment for hyperuricaemia and gout? 669 72

Of 29 524 hospitalised medical patients monitored in a drug surveillance programme 1835 (6.2%) received the xanthine oxidase inhibitor allopurinol. After the exclusion of skin reactions adverse effects were attributed to this drug in 33 (1.8%) patients, the most frequent being haematological abnormalities (11 patients, 0.6%) and diarrhoea and drug fever (5 each, 0.3%). Adverse effects were dose-related. Reactions were unrelated to age, weight, reason for therapy, admission blood urea, or albumin concentrations. Acute exacerbation of gout was troublesome in 3 patients (1 in 600 exposed).
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PMID:Acute adverse reactions attributed to allopurinol in hospitalised patients. 724 70

Enzyme-induced liberation of hard-segment-containing components from polyurethanes was evaluated using two 14C-labeled polyurethanes. A polyester urea-urethane and polyether urea-urethane were synthesized from toluene-2,4-diisocyanate (TDI)/polycaprolactone diol (PCL) or TDI/polyethylene glycol (PEO) with 14C-labeled ethylene diamine. Both materials were characterized using electron spectroscopy for chemical analysis (ESCA), differential scanning calorimetry (DSC), size exclusion chromatography, and material chemistry by Fourier transform infrared (FTIR) spectroscopy. Biodegradation assays were carried out using cholesterol esterase (CE), collagenase (CO), cathepsin B (CB), and xanthine oxidase (XO) at the pH optimum conditions for each enzyme at 37 degrees C. Biodegradation was analyzed by monitoring the release of radiolabel, by weight change, and by surface analysis using scanning electron microscopy. The polyester urea-urethane was shown to be susceptible to enzymatic degradation above the effect of the buffer control solution by the CE but not by the other enzyme systems as monitored by radiolabel released. In the initial period of incubation, the rate of degradation was increased for all systems, including buffer controls; however, the rates dropped off rapidly by day 28. The change in weight data for the polyester urea-urethane and polyether urea-urethane showed no enzyme-dependent biodegradation above the buffer controls. However, in sodium acetate buffer at pH = 5, the polymers showed a significant weight loss relative to other buffers. In conclusion, this study showed that the biological component responsible for the onset of the biodegradation process is more likely the result of a multitude of biologically mediated compounds acting synergistically, with the process being enhanced by physical parameters such as material dissolution. In addition characterization of surface and bulk chemistry as well as material structure evaluation have been shown to be essential to interpret degradation data.
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PMID:Enzyme-biomaterial interactions: effect of biosystems on degradation of polyurethanes. 842 Oct 4


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