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)

The metabolic causes for immune impairment in patients with severe chronic inflammatory diseases have not been clearly defined. Recently, the overproduction of poly(ADP-ribose) in resting lymphocytes with unrepaired DNA strand breaks has been suggested to contribute to immune dysfunction in adenosine deaminase-deficient patients. Our experiments have determined to what extent DNA damage and poly(ADP-ribose) synthesis might also explain the impaired mitogen responsiveness of PBL exposed to toxic oxygen species. Treatment of normal resting human lymphocytes with xanthine oxidase and hypoxanthine dose-dependently induced DNA strand breaks and triggered the rapid synthesis of poly(ADP-ribose). Subsequently, NAD+ and ATP pools decreased precipitously. Lymphocytes exposed previously to the enzymatic oxidizing system did not synthesize DNA after stimulation with PHA. However, if the medium was supplemented with 3-aminobenzamide or nicotinamide, two compounds that inhibit poly(ADP-ribose) formation, cellular NAD+ and ATP pools were preserved, and the lymphocytes responded vigorously to a mitogenic challenge. Excessive poly(ADP-ribose) synthesis, provoked by DNA strand breakage, may represent a common pathway that connects the immunodeficiency syndromes associated with (a) exposure of lymphocytes to toxic oxygen species during chronic inflammatory states, (b) adenosine deaminase deficiency, and (c) certain DNA repair disorders.
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PMID:Lymphocyte dysfunction after DNA damage by toxic oxygen species. A model of immunodeficiency. 395 May 45

Because of the importance of adenosine deaminase (ADA) in brain function, a histochemical method for visualizing the enzyme in various areas of the human neuraxis was devised, using an MTT [3-(4,5-dimethyl-thiazolyl-2)-2,5-diphenyltetrazolium bromide] method and glutaraldehyde fixation. Controls consisted of preincubation without the substrate, incubation with omission successively of the substrate, MTT tetrazolium, purine nucleoside phosphorylase (PNP), xanthine oxidase (XO), NaCl, boiling for 20 min prior to fixation and incubation, and of incubation of sections with two powerful inhibitors of the enzyme, i.e., 2'-deoxycoformycin and EHNA [erythro-9-(2-hydroxy-3-nonyl)adenine.HCl]. The positive reaction consisted of the deposition of brownish-purple granules, as well as a diffuse nongranular reaction in the cytoplasm of neurons and glial cells, and in the interstitial spaces. Sections from 15 different areas in four brains were examined by this method. This is the first time that adenosine deaminase has been demonstrated histochemically in the nervous system of humans or of any other species.
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PMID:Histochemical demonstration of adenosine deaminase in the human neuraxis. Preliminary observations. 404 5

During phagocytosis and membrane perturbation, mouse macrophages generate superoxide in direct proportion to their intracellular adenosine deaminase activity. It is proposed that since adenosine deaminase controls the amount of substrate available to xanthine oxidase, and the latter produces superoxide during turnover of its substrates, the purine salvage pathway is an important contributor to the superoxide requirement of macrophages. It is further proposed that this may be the basis for the mechanism of the association of adenosine deaminase deficiency with immunodeficiency.
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PMID:Adenosine deaminase activity and superoxide formation during phagocytosis and membrane perturbation of macrophages. 626 29

Plasmodium falciparum trophozoites were isolated by mechanical rupture of infected human erythrocytes followed by a series of differential centrifugation steps. After lysis with sonication, the 100 000 x g supernatant of parasites and uninfected host cells was used to determine the specific activities of a number of enzymes involved in purine and pyrimidine metabolism. P. falciparum possessed the purine salvage enzymes: adenosine deaminase, purine nucleoside phosphorylase, hypoxanthine-guanine phosphoribosyltransferase (PRTase), xanthine PRTase, adenine PRTase, adenosine kinase. The last two enzymes, however, were present at much lower activity levels. Hypoxanthine was converted (presumably via IMP) into adenine and guanine nucleotides only in the presence both of supernatant and membrane fractions of P. falciparum. Two enzymes involved in the de novo synthesis of pyrimidines, orotic acid PRTase, and orotidine 5'-phosphate decarboxylase, were present in parasite extracts as were the enzymes for pyrimidine nucleotide phosphorylation: UMP-CMP kinase, dTMP kinase, nucleoside diphosphate kinase. Xanthine oxidase, CTP synthetase, cytidine deaminase and several kinases for the salvage of pyrimidine nucleosides were not detected in the parasites. Both phosphoribosyl pyrophosphate synthetase and uracil PRTase were present but at low activity levels. Human erythrocytes displayed similar but not identical enzyme patterns. Enzyme specific activities, however, were generally much lower than those of the corresponding parasite enzymes.
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PMID:Enzymes of purine and pyrimidine metabolism from the human malaria parasite, Plasmodium falciparum. 628 90

Phagocytosis and membrane perturbation in mouse macrophages results in an increased superoxide ion production which is in direct proportion to the concomitant increase in adenosine deaminase activity. Since adenosine deaminase activity controls the amount of substrate available to xanthine oxidase, and the latter produces superoxide during turnover of its substrates, it is proposed that the purine salvage pathway is an important source of the superoxide requirement of macrophages. It is further proposed that this may be the basis, at least in part, for the mechanism of the association of immunodeficiency with adenosine deaminase deficiency.
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PMID:Positive correlation between adenosine deaminase activity and superoxide formation during phagocytosis. 630 Feb 72

Neutrophils and macrophages generate superoxide anion during the respiratory burst in response to various stimuli, including microorganisms. It has recently been proposed that an important source of superoxide anion during the respiratory burst that stimulates murine macrophages is the sequential metabolism of adenosine via adenosine deaminase and xanthine oxidase to uric acid. Thus, the immunodeficiency state associated with adenosine deaminase deficiency may be caused at least in part by a defect in superoxide anion generation. The ability to generate superoxide anion of stimulated neutrophils isolated from three children with adenosine deaminase deficiency and associated severe combined immunodeficiency was tested. Neutrophils from all three patients were able to generate superoxide anion. One of these generated 19.1 nmol cytochrome c reduced/10(6) cells (normals = 5.3-33.0, mean 18.4 +/- 7.1) while the other two generated low normal levels. Neutrophils from all three children also generated more superoxide anion after addition of exogenous adenosine deaminase. Thus, no evidence to support a role for cellular adenosine deaminase in the release of superoxide anion by stimulated neutrophils was found. Although neutrophils from patients deficient in adenosine deaminase appear to have no inherent defect in the generation of superoxide anion, the abnormally high concentrations of adenosine found in the plasma of these patients could, in vivo, secondarily, inhibit superoxide anion release.
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PMID:Adenosine deaminase is not required for the generation of superoxide anion. 632 Oct 74

The purine metabolism of four cases with marked hypouricemia (serum uric acid concentration of less than 0.018 mmol/l) from three Japanese families was investigated. Erythrocyte adenosine deaminase (EC 3.5.4.4) and purine-nucleoside phosphorylase (EC 2.4.2.1) activities of the patients were within the normal ranges. Urinary hypoxanthine and xanthine concentrations were 0.096-0.397 mmol/l and 0.743-1.717 mmol/l, respectively. Xanthine oxidase (EC 1.2.3.2) activities in the jejunal mucosa of the two normal controls were 0.257 and 0.283 units/g protein, while those of three of the patients were extremely low and could not be determined. The findings of these biochemical features may indicate that the four patients have hereditary xanthinuria. In order to study the purine metabolism in the hypouricemic condition of this disorder, a single oral dose of allopurinol (4-hydroxypyrazolo[3,4-d]pyrimidine) was administered in one case. The excretion pattern of allopurinol and oxypurinol (4,6-dihydroxypyrazolo[3,4-d]pyrimidine) in the urine of the patient was similar to that of a normal control male. These data suggest that some residual enzyme activity may be functioning in vivo, although the presence of xanthine oxidase could not be detected.
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PMID:Biochemical studies on the purine metabolism of four cases with hereditary xanthinuria. 642 23

Erythrocytes of five strains of mice had ATP concentrations of ca 2.7 mumol/ml packed cells, while those of CBA mice were 23% lower, and those of BALB/C mice were 40% lower. The ratio of the concentrations of ATP and GTP were ca 3.3 in four strains but greater than 27 in three other strains. When erythrocytes from different mouse strains were incubated with radioactive precursors, appreciable strain differences were found in the apparent activities of adenine and hypoxanthine-guanine phosphoribosyltransferase, adenosine kinase, adenosine deaminase, guanine deaminase and xanthine oxidase. The activities of adenosine deaminase and guanine deaminase in sera of mice of different strains also varied.
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PMID:Variation in erythrocyte purine metabolism among mouse strains. 668 81

Adenosine kinase, adenosine deaminase, hypoxanthine phosphoribosyltransferase, inosine-nucleoside phosphorylase, 5'-AMP deaminase and 5'-IMP nucleotidase were identified in cell-free extracts of duckling erythrocytes; no evidence for 5'-AMP nucleotidase and xanthine oxidase activity was found. The Km values for the duckling red cell enzymes were similar to those reported for human erythrocytes. Plasmodium lophurae extracts demonstrated similar enzyme activities except for 5'-AMP deaminase and 5'-IMP nucleotidase which were absent. It is proposed that during infection erythrocytic AMP is catabolized to IMP, inosine and hypoxanthine; the hypoxanthine is taken up by the plasmodium, utilized to form IMP, and this in turn is converted into adenine and guanine nucleotides.
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PMID:Purine metabolizing enzymes of Plasmodium lophurae and its host cell, the duckling (Anas domesticus) erythrocyte. 678 22

A new spectrophotometric method for the determination of adenosine deaminase is described. Adenosine is deaminated to inosine, the latter is cleaved by an inosine-guanosine specific nucleoside phosphorylase to hypoxanthine and ribose-1-phosphate. Hypoxanthine can be oxidized further to uric acid by xanthine oxidase or to allantoin by xanthine oxidase and uricase. The hydrogen peroxide formed in these reactions is reduced by catalase to water. In the presence of high concentrations of ethanol, equivalent amounts of acetaldehyde are produced. The acetaldehyde is oxidized NAD(P) dependent and the production rate of NAD(P)H is recorded at 334 nm. The new method is suitable for the detection of adenosine deaminase in whole blood, lymphocytes, sera and tissues.
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PMID:A new spectrophotometric assay for enzymes of purine metabolism. IV. Determination of adenosine deaminase. 736 76


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