Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biochemical impairments in spleen immunocompetent cells (T- and B-lymphocytes) were revealed in host (C3HA mice) of transplantable and ortoaminoazotoluol-induced hepatomas in the course of their growth. As soon as hepatoma emerged (chemical carcinogenesis), the activity of adenosine deaminase and purine nucleoside phosphorylase in T- and B-lymphocytes were found to be reduced 2-6 and 7-10-fold, respectively in parallel with the impairment of their immune system. These alterations were accompanied by the increase in concentrations of dGTP in T-lymphocytes (5.4-fold) and of dATP in B-lymphocytes (4-fold) as well as with the inhibition of DNA synthesis, predominantly in T-lymphocytes. In both T- and B-lymphocytes, the dCTP pool was decreased. In the spleen, T- and B-lymphocytes of mice carrying transplantable 22 hepatoma 22 by the moment of its maximal growth (5th day), the DNA synthesis was inhibited as revealed by the reduction of (a) thymidine kinase activity, (b) rate of the labeled thymidine incorporation into DNA, and (c) intracellular dTTP and dCTP concentrations. In latter periods (from 8th day up to the moment of death), drastic stimulation of DNA synthesis in spleen T- and B-lymphocytes was observed irrespective of the impairments in the immune function and the decrease of the adenosine deaminase activity. In the course of growth of both transplantable and induced solid hepatomas in host spleen T- lymphocytes, the activity of the CTP-dependent thymidine kinase isoenzyme increased, coinciding in time with the activation of antigen-specific T-suppressors in the same organ.
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PMID:[Changes in DNA and purine nucleotide synthesis in lymphoid cells and sensitivity to glucocorticoids associated with the impairment of differentiation and immune function in mice during tumor growth. Spleen T- and B-lymphocytes]. 308 34

By monitoring the in vivo incorporation of low concentrations of radiolabeled adenine into acid-soluble compounds, we observed the unusual accumulation of two nucleosides in Saccharomyces cerevisiae that were previously considered products of nucleotide degradation. Under the culture conditions used in the present study, radiolabeled adenosine was the major acid-soluble intracellular derivative, and radiolabeled inosine was initially detected as the second most prevalent derivative in a mutant lacking adenine aminohydrolase. The use of yeast mutants defective in the conversion of adenine to hypoxanthine or to AMP renders very unlikely the possibility that the presence of adenosine and inosine is attributable to nucleotide degradation. These data can be explained by postulating the existence of two enzyme activities not previously reported in S. cerevisiae. The first of these activities transfers ribose to the purine ring and may be attributable to purine nucleoside phosphorylase (EC 2.4.2.1) or adenosine phosphorylase (EC 2.4.2.-). The second enzyme converts adenosine to inosine and in all likelihood is adenosine aminohydrolase (EC 3.5.4.4).
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PMID:Adenosine accumulation in Saccharomyces cerevisiae cultured in medium containing low levels of adenine. 308 89

The hypothesis that decreased T cell function in the elderly involves an increased number of less differentiated T cells was examined. Three markers known to change during thymocyte development were analyzed; ratio of adenosine deaminase (ADA) to purine nucleoside phosphorylase (PNP), lactate dehydrogenase (LD) H/M subunit ratios and the T cell associated antigens, T3, T4, T8 and T10. Cells tested were from 10 old (greater than 75 years) and 10 young (less than 35 years) persons with equal numbers of males and females in each group. Before analysis, cells were purified into three groups; unfractionated, and monocyte depleted T cell and B cell enriched populations. Results for ADA/PNP ratios showed no significant differences between old and young in any of the fractions analyzed. H/M ratios however, were significantly reduced in all three fractions from old donors when compared with young. Surface marker distribution pattern as illustrated by the T3 - (T4 + T8) difference was lower in samples from old donors but not significantly so. There was a very significant reduction in percent cells positive for T3 in all three fractions from old persons. Although some of the changes seen in these markers could be due to a failure of normal differentiation, they could also be caused by the general phenomenon of altered gene expression known to occur with advanced age in a variety of non-lymphoid cells. The absence of any difference in the ADA/PNP ratio suggests that T cell dysfunction in the elderly may not be due to increased numbers of less differentiated cells as a result of thymic involution.
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PMID:Do immature T cells accumulate in advanced age? 308 35

The intraerythrocytic human malaria parasite, Plasmodium falciparum, requires a source of hypoxanthine for nucleic acid synthesis and energy metabolism. Adenosine has been implicated as a major source for intraerythrocytic hypoxanthine production via deamination and phosphorolysis, utilizing adenosine deaminase and purine nucleoside phosphorylase, respectively. To study the expression and characteristics of human malaria purine nucleoside phosphorylase, P. falciparum was successfully cultured in purine nucleoside phosphorylase-deficient human erythrocytes to an 8% parasitemia level. Purine nucleoside phosphorylase activity was undetectable in the uninfected enzyme-deficient host red cells but after parasite infection rose to 1.5% of normal erythrocyte levels. The parasite purine nucleoside phosphorylase was not cross-reactive with antibody against human enzyme, exhibited a calculated native molecular weight of 147,000, and showed a single major electrophoretic form of pI 5.4 and substrate specificity for inosine, guanosine and deoxyguanosine but not xanthosine or adenosine. The Km values for substrates, inosine and guanosine, were 4-fold lower than that for the human erythrocyte enzyme. In these studies we have identified two novel potent inhibitors of both human erythrocyte and parasite purine nucleoside phosphorylase, 8-amino-5'-deoxy-5'-chloroguanosine and 8-amino-9-benzylguanine. These enzyme inhibitors may have some antimalarial potential by limiting hypoxanthine production in the parasite-infected erythrocyte.
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PMID:Expression of human malaria parasite purine nucleoside phosphorylase in host enzyme-deficient erythrocyte culture. Enzyme characterization and identification of novel inhibitors. 309 93

T-cell acute lymphoblastic leukemia (ALL) comprises a third of the cases of childhood ALL in Israel. This high proportion of T-ALL is most probably due to a deficiency in pre-B/common ALL. The T-ALL patients had significantly worse 4-yr survival compared to standard risk or non-T high risk patients. In view of these special epidemiologic and clinical features a study of the immunophenotype of all consecutive cases of T-ALL and T-non Hodgkin's lymphoma (NHL) observed in our medical center was performed. Twenty-eight ALL and 3 NHL patients were studied and their cells characterized using a panel of monoclonal antibodies, TdT reactivity and E-rosette formation. Assays of the activities of adenosine deaminase (ADA) and purine nucleoside phosphorylase (NP) were also performed. Based on the surface antigen expression, the tumor cells could be classified into one of the three known developmental stages of T cells. It was found that the immunophenotype of the T-ALL cases in Israel was similar to that observed in other countries. Considerable heterogeneity of surface antigen expression was found and in a number of cases the phenotype analysis was not easily reconciled with models of T-cell ontogeny. The activities of ADA and NP were correlated with the developmental stage, as defined by the surface antigenic expression. Contrary to observations on normal T-cells, where ADA activity decreases and NP activity increases as T-cells mature and differentiate, this was not found in the malignant T cells. These findings as well as the existence of atypical immunophenotypes suggest that the leukemic T cell has an abnormal gene expression.
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PMID:T-cell acute lymphoblastic leukemia in Israel: clinical and laboratory features. 309 94

Cell lines were established which produced high titers (approximately 10(6) infectious units per ml) of amphotropic, replication-defective recombinant retroviruses which transduced sequences encoding either human purine nucleoside phosphorylase (PNP) or adenosine deaminase (ADA). These viruses also contained a human hypoxanthine phosphoribosyltransferase gene as a selectable marker and a mouse metallothionein promoter (MMP) sequence just upstream from the PNP or ADA genes. Virus structure was maintained through the replication cycle if a short (216-base pair) MMP sequence was used. However, the use of a longer (1,834-base pair) MMP sequence resulted in the deletion of a significant portion of the recombinant virus genome, including the transcriptional regulatory elements of the MMP sequence. Northern analysis indicated a predominance of genome length transcripts in cells infected with deleted virus. The demonstration of substantial human PNP or ADA activity in virus-infected mouse fibroblasts by isozyme analysis suggested that active gene product was translated from either spliced or bicistronic message. The deleted ADA and PNP viruses were introduced into mouse hematopoietic stem cells by cocultivating freshly explanted bone marrow with virus producer cells. The infected marrow cells were injected into irradiated, syngeneic recipient mice, and the presence of integrated ADA or PNP proviral sequences was demonstrated in the DNA of spleen colonies by Southern analysis. Failure of these integrated proviral sequences to express active, human isozyme in spleen colony tissue indicated the existence of some regulatory constraint not active in cultured mouse cells.
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PMID:Human purine nucleoside phosphorylase and adenosine deaminase: gene transfer into cultured cells and murine hematopoietic stem cells by using recombinant amphotropic retroviruses. 310 47

Depressed activities of the following purine enzymes have been shown to result in immunodeficiencies: adenosine deaminase (ADA), hypoxanthine-guanine phosphoribosyltransferase (HGPRT), and purine nucleoside phosphorylase (PNP). These enzymes and adenosine kinase (AK) were measured in cord blood lymphocytes of premature and small-for-gestational age infants since they have partial immunodeficiencies of unknown biochemical etiology which can persist for many years. We also measured these enzymes in 3 infants with various immunodeficiencies. Activities were compared with appropriate matched control groups. The results indicated normal ADA and PNP but significantly depressed AK (P less than 0.05) and HGPRT (P less than 0.001) activities in 10 premature/SGA infants when compared to 35 full-term normal infants. In the 3 immunodeficient children the results were as follows: Child 1 had a 2- to 3-fold decrease in ADA with normal PNP and AK activities; Child 2 had a 2- to 3-fold decrease in AK, 4-fold decrease in HGPRT with normal PNP and ADA activities; Child 3 had confirmed AIDS and a 4-fold decrease in ADA, 6-fold decrease in HGPRT with normal PNP activity. The possible role of these depressed purine enzyme activities found in lymphocytes is discussed in relation to the imparied immunity seen in these infants.
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PMID:Activities of purine metabolising enzymes in lymphocytes of neonates and young children: correlates with immune function. 311 34

The courses of six patients with adenosine deaminase (ADA) and two with purine nucleoside phosphorylase (PNP) deficiencies were evaluated before and after therapy. The heterogeneity of immunologic and clinical parameters was striking in each enzyme deficiency. In both PNP and ADA deficiency, some patients had very low immunoglobulin levels, while others had normal levels. T-cell function was always low in patients with ADA deficiency. In the two patients with PNP deficiency, contrary to the classical descriptions of this disorder, T-cell function fluctuated with time. Five ADA-deficient patients were treated with irradiated normal red-cell transfusions as a form of enzyme replacement and showed no lasting benefit. Three of the ADA-deficient patients and one of the PNP-deficient patients were given transplants of haploidentical parental bone marrow stem cells without pretransplant immunosuppression. In the PNP-deficient patient, chimerism has not been documented on enzymatic testing. One ADA-deficient patient has demonstrated long-term engraftment with good B- and T-cell function. Haploidentical bone marrow transplantation is currently the preferred therapy for enzyme-deficient patients with absent T-cell function who do not have an HLA-identical donor, as it may result in a lasting reconstitution of immune function. In those patients with unsatisfactory responses to transplantation, however, specific enzyme replacement or gene therapy may be considered in the future.
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PMID:Adenosine deaminase and purine nucleoside phosphorylase deficiencies: evaluation of therapeutic interventions in eight patients. 311 34

Mobilization of the ribose moiety of purine nucleosides as well as of the amino group of adenine may be realized in Bacillus cereus by the concerted action of three enzymes: adenosine phosphorylase, adenosine deaminase, and purine nucleoside phosphorylase. In this pathway, ribose-1-phosphate and inorganic phosphate act catalytically, being continuously regenerated by purine nucleoside phosphorylase and adenosine phosphorylase, respectively. As a result of such a metabolic pathway, adenine is quantitatively converted into hypoxanthine, thus overcoming the lack of adenase in B. cereus.
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PMID:Phosphorylase-mediated mobilization of the amino group of adenine in Bacillus cereus. 312 63

Growth on Trypanosoma musculi in the murine host was limited by the availability of host purines. A portion of the spleen cells of infected mice (many of them granulocytes) displayed high levels of adenosine deaminase (ADA) and purine nucleoside phosphorylase, probably as a compensatory response to extracellular purine deficiency. Injections of adenosine or 2-deoxycoformycin stimulated significant increases in the growth of parasites. 2-Deoxycoformycin treatment also diminished parasite-induced splenomegaly. Treatment of mice with polyethylene glycol-modified ADA, a slowly catabolized form of ADA, had no effect on the course of T. musculi infection, indicating that the parasites can utilize purines other than adenosine. The apparent competition between parasites and host cells for available purines suggests that depletion of extracellular purines should be considered as an approach to treating extracellular trypanosome infections.
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PMID:The availability of purines influences both the number of parasites and the splenocyte levels of purine-metabolizing enzymes in trypanosome-infected mice. 312 45


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