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)

A method is presented for the two-dimensional thin-layer chromatographic screening of purines, pyrimidines and their nucleosides in the urine. Prior to chromatography, isolation of these substances from the urine is performed by anion-exchange column chromatography. Purines and pyramidines are quantitatively eluted with formic acid 0.01 M and 4 M respectively. The results of recovery and stability experiments are given. Normal excretory patterns are presented. Also results in patients with various diseases are shown: ornithine transcarbamylase deficiency, adenosine deaminase deficiency, purine nucleoside phosphorylase deficiency, adenine phosphoribosyltransferase deficiency, xanthine oxidase deficiency and hypoxanthine-guanine phosphoribosyltransferase deficiency. Finally the pattern of a patient on treatment with allopurinol is given.
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PMID:Two-dimensional thin-layer chromatography for the screening of disorders of purine and pyrimidine metabolism. 9 7

A screening method has been established for PNP deficiency. This enzyme activity in dried blood absorbed on filter paper can be detected by the formation of a blue insoluble formazan with a gel containing inosine, xanthine oxidase, MTT-tetrazolium, and phenazine methosulfate. The color change is very clear and definite and no false results have been obtained in the testing of 256 enzyme-positive and 107 enzyme-negative samples. The enzyme activity in dried blood on filter paper is so stable at room temperature that samples can be mailed. A screening method for ADA deficiency was developed, also depending on the color change of MTT-tetrazolium. Although the test is slightly more expensive than that developed by Moore and Meuwissen, its accuracy is greater. A common screening method for detecting deficiencies of either PNP or ADA is described.
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PMID:Screening for primary immunodeficiencies associated with purine nucleoside phosphorylase deficiency or adenosine deaminase deficiency. 40 94

The importance of intact adenosine deaminase (ADA) activity in the generation of superoxide anion by xanthine oxidase has been disputed in studies using human neutrophils or mouse macrophages. The latter demonstrated a positive correlation between ADA activity and superoxide production during phagocytosis. The immunodeficiency in inherited ADA deficiency was related to a defect in this process. Since there is considerable interspecies variation in the tissue distribution of xanthine oxidase, the metabolism of [8-14C]deoxyadenosine (dAR), the toxic metabolite which accumulates in inherited ADA deficiency, was investigated in human peritoneal macrophages. Evaluation of the distribution of radiolabel in both cell and medium demonstrated that human macrophages with intact ADA metabolize dAR under physiological conditions to deoxyinosine and hypoxanthine exclusively. The hypoxanthine is further metabolized within the cell to ATP and GTP, via IMP. No xanthine or uric acid could be detected, confirming that in human macrophages xanthine oxidase activity is insignificant, as it is in most other human cells and tissues, except liver and intestinal mucosa. Thus production of superoxide radicals in such cells via this route would be impossible, and consequently unaffected either by ADA deficiency or the xanthine oxidase inhibitor allopurinol.
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PMID:Superoxide radicals, immunodeficiency and xanthine oxidase activity: man is not a mouse! 298 25

Coformycin, which is an inhibitor of adenosine deaminase, significantly inhibited in vitro blastogenic responses of human lymphocytes to both phytohaemagglutinin (PHA) and pokeweed mitogen (PWM), whereas blastogenic responses to bacterial lipopolysaccharide (LPS) were rather enhanced by the addition of coformycin. Blastogenic responses of lymphocytes to PHA and PWM were markedly suppressed by the addition of adenosine, which is a substrate of adenosine deaminase. Allopurinol, which is an inhibitor of xanthine oxidase, inhibited blastogenic responses of human lymphocytes to PHA, PWM, and bacterial LPS. Inosine (a substrate of purine nucleoside phosphorylase) and hypoxanthine (a substrate of xanthine oxidase) showed no or only a small effect on blastogenic responses of human lymphocytes. These results suggest that adenosine deaminase activity is associated with the T-cell response but not with the B-cell response and that the impaired T-cell response in adenosine deaminase deficiency is the result of intracellular retention of adenosine in T cells. The results also suggest that purine nucleoside phosphorylase or xanthine oxidase activity is associated with both T- and B-cell responses.
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PMID:Purine metabolic enzymes in lymphocytes. IV. Effects of enzyme inhibitors and enzyme substrates on the blastogenic responses of human lymphocytes. 392 75

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

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

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

Purines and pyrimidines are of interest owing to their significance in processes in living organisms. Mass spectrometry is a promising analytical tool utilized in their analysis. Two atmospheric pressure ionization (API) methods (electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI)) in both negative and positive modes applied to selected purine and pyrimidine metabolites (markers of inherited metabolic disorders) were studied. APCI is less sensitive to alkali metal cations present in a sample and offers higher response than ESI for studied compounds. Both of the techniques afford quasi-molecular ions, but fragmentation also occurs to a certain extent. However, the application of collision-induced dissociation of quasi-molecular ions is essential to confirm a certain metabolite in a sample. Fragmentation of both positive and negative ions was evaluated using multi-stage mass spectrometric experiments. Typical neutral losses correspond to molecules NH(3), H(2)O, HCN, CO, H(2)NCN, HNCO and CO(2). The ion [NCO](-) arises in the negative mode. The cleavage of the glycosidic C-N bond is characteristic for relevant metabolites. Other neutral losses (CH(2)O, C(2)H(4)O(2) and C(3)H(6)O(3)) originate from fragmentation of the glycosidic part of the molecules. In addition to fragmentation, the formation of adducts of some ions with applied solvents (H(2)O, CH(3)OH) was observed. The composition of the solution infused into the ion source affects the appearance of the mass spectra. Tandem mass spectra allow one to distinguish compounds with the same molecular mass (uridine-pseudouridine and adenosine-2'-deoxyguanosine). Flow injection analysis APCI-MS/MS was tested on model samples of human urines corresponding to adenosine deaminase deficiency and xanthine oxidase deficiency. In both cases, the results showed potential diagnostic usefulness.
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PMID:Atmospheric pressure ionization mass spectrometry of purine and pyrimidine markers of inherited metabolic disorders. 1248 84