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:3.5.4.17 (adenosine deaminase)
5,206 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analysis of human-rodent hybrids showed the following: the assignment of the ADA1 structural gene to chromosome 20; the identification in hybrids of a new ADA, referred to as ADAx, with a migration more rapidly anodal than ADAd and less rapidly anodal than ADA1 (product of allele 1 or 2); ADAx and d are formed by ADA1 and ADCP (an adenosine deaminase complexing protein). ADCP synthesis is controlled, at least, by a gene (ADCP2) localized on chromosome 2, probably in the IDH1 region; the combined action of another gene (ADCP1), assigned by other authors to chromosome 6, could be neither proved nor disproved, if this gene exists, it must be on 6p or in the 6qter region; the presence of chromosomes 20, 2, and 6 does not constitute a sufficient condition for the formation of ADAx and d, in either the hybrids or the human strains or lines: other factors intervene in its formation, i.e., an interaction between the culture medium, the human parental strain or line, and the rodent parental line.
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PMID:[Genetic and epigenetic control of adenosine deaminase expression. Analysis of human and man-mouse hybrid cells (author's transl)]. 697 23

dATP, dADP, and dAMP equalled or exceeded the depleted levels of ATP, ADP, and AMP in erythrocytes from two children with adenosine deaminase (ADA; EC 3.5.4.4) deficiency. dATP and dADP were identified in the mononuclear cells of only one child. The levels of deoxyadenosine compounds fell dramatically after enzyme replacement therapy and were no longer detectable in the urine or in mononuclear cells. Erythrocyte adenosine nucleotide levels showed a corresponding increase. Intact erythrocytes prior to treatment contained adenine, presumed to be from deoxyadenosine degraded during extraction. Adenosine at high concentrations in vitro increased both dATP and ATP levels and decreased intracellular deoxyadenosine levels. There was no significant deamination of either [8-14C]adenosine or deoxyadenosine by intact ADA-deficient erythrocytes. About 90% of adenosine was metabolized to ATP at substrate concentrations from 10-100 microM, compared to 40-60% of deoxyadenosine metabolized to dATP. These studies suggest that (i) high intracellular deoxyadenosine levels may be necessary in vivo to sustain the raised dATP levels in ADA deficiency. (ii) When ADA is inhibited or absent, deoxyadenosine is removed rapidly from the circulation by the human erythrocyte utilizing an adenosine transport system linked to both ADA and adenosine kinase (EC 2.7.1.20).
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PMID:Formation and degradation of deoxyadenosine nucleotides in inherited adenosine deaminase deficiency. 698 23

A deficiency of the enzyme adenosine deaminase is associated with an autosomal recessive form of severe combined immunodeficiency disease in man. The molecular forms of the normal human enzyme have now been well characterized in an effort to better understand the nature of the enzyme defect in affected patients. In some human tissues adenosine deaminase exists predominantly as a small molecular form while in other tissues a large form composed of adenosine deaminase (small form) and an adenosine deaminase-binding protein predominates. The small form of the enzyme purified to homogeneity by antibody affinity chromatography is a monomer of native molecular weight of 37,600. The adenosine deaminase-binding protein, purified by adenosine deaminase affinity chromatography, appears to be a dimer of native molecular weight 213,000 and contains carbohydrate. Based on direct binding measurements, chemical cross-linking studies and sedimentation equilibrium analyses, small form adenosine deaminase has been shown to combine with purified binding protein in a molar ratio of 2:1 respectively to produce the large form adenosine deaminase. Reduced, but widely ranging levels of adenosine deaminating activity, have been reported in various tissues of adenosine deaminase deficient patients. Further, the characteristics of this residual enzyme activity have been analyzed immunochemically to substantiate genetic heterogeneity in this disorder. While many types of immunodeficiency are currently recognized in man, in most cases the molecular defect is unknown. The discovery of a deficiency of the enzyme, adenosine deaminase, ADA, (EC 3.5.4.4), in some patients with severe combined immunodeficiency disease represented an early clue to the pathogenesis of immune dysfunction at the molecular level 1-4. Affected patients with markedly reduced levels of ADA exhibit a defect of both cellular and humoral immunity characterized clinically by severe recurrent infections with a fatal outcome if untreated. Attempts to elucidate the nature of the genetic mutation(s) leading to the reduction of ADA activity in these immunodeficient patients have been complicated in part by an incomplete understanding of the nature of ADA in normal tissues. In this review we will consider the structural characteristics of the normal and mutant forms of ADA as they are currently understood.
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PMID:Analysis of normal and mutant forms of human adenosine deaminase - a review. 698 97

1. In washed guinea-pig brain slices, adenosine uptake inhibitors potentiated the responsiveness of cAMP to adenosine, while an adenosine deaminase inhibitor, 2'-deoxycoformycin, was without effect. 2. In the isolated guinea-pig ileum, uptake was important in terminating the inhibitory action of adenosine on nerve-mediated contractions whereas the ADA inhibitor did not affect the ileum or its responses to adenosine in any way. 3. Adenosine given to mice (100 mg/kg i.p.) or guinea-pigs (250 mg/kg i.p.) caused a small, transient fall in body temperature, accompanied by skeletal-muscle relaxation. 4. In mice this temperature fall was potentiated by the uptake blocker dilazep, although only marginally so by the uptake blocker dipyridamole. The ADA-inhibitor also potentiated the pharmacological responses to adenosine. 5. Responses to adenosine in the guinea-pig were less affected by treatment with uptake or ADA-inhibitors, except when given in combination.
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PMID:Potentiation of pharmacological responses to adenosine, in vitro and in vivo. 706 Sep 20

Adenosine deaminase (adenosine aminohydrolase, EC3.5.4.4) has been purified from human erythrocytes using a simple chromatographic procedure. Purified enzyme was obtained from individuals who were homozygous for the principal isozyme (ADA 1) as well as from individuals who were heterogyzous for the major variant (ADA 2-1). Although ADA 1 and ADA 2-1 are electrophoretically distinguishable, they have many common physical and catalytic properties. No significant differences between the two isozymic forms were found in measurements of molecular weight, catalytic activity in the presence of various substrates and inhibitors, pH optimum, turnover number, and stability in conditions of both high and low pH. ADA 2-1 was, however, substantially less stable than ADA 1 with respect to thermal denaturation. These studies support the idea that adenosine deaminase activity in erythrocytes is lower in those individuals who possess the variant form of the enzyme.
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PMID:Physical and catalytic properties of the isozymes of adenosine deaminase from human red blood cells. 714 44

Phenotypes and gene frequencies of the erythrocyte enzyme adenosine deaminase were determined in samples from Schleswig-Holstein, Portugal, Brazil, and South Africa (Bantu-Xhosa and White). In the Portugal population the phenotypes ADA 5-1 and ADA 5-2 were found.
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PMID:[Phenotype distribution and gene frequencies of adenosine deaminase in Schleswig-Holstein compared with samples from Portugal, Brazil, and South Africa (Bantu-Xhosa and whites) (author's transl)]. 723 39

The nature of the defect of a female baby who died of severe combined immunodeficiency (SCID) disease associated with adenosine deaminase deficiency (ADA-) was investigated. Since tissue or tissue culture material was not available for subsequent studies, the expression of ADA in her cells was investigated in the somatic cell hybrid clones derived from a fusion between the lymphocytes from one of her two obligate heterozygote parents and thymidine kinase deficient Chinese hamster (a3) fibroblasts. The results of analyses of the human chromosomes and biochemical markers in 12 independent clones and 27 subclones indicated that the ADA deficiency in the patient is determined probably by a mutation in the structural gene for ADA in chromosome 20 leading either to the production of catalytically defective molecules or to the cessation of the production of ADA. Incidentally, the involvement of chromosome 2, which carries a gene for adenosine deaminase complexing protein (ADCP), in the causation of ADA deficiency was excluded. The in vitro approach through the cells from an obligate heterozygote described in this paper may have a general application in pursuing studies on other cases of inborn errors of metabolism whenever the material from the affected individuals (i.e., the homozygotes) is not available or not suitable for direct investigations.
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PMID:Basic defect in the expression of adenosine deaminase in ADA- SCID disease investigated through the cells of an obligate heterozygote. 723 21

We investigated whether rhesus monkey CD34+CD11b- hematopoietic stem cells can be transduced with recombinant retroviruses carrying the human adenosine deaminase (hADA) gene by co-cultivation with a virus-producing cell line. Following autologous transplantation, polymerase chain reaction (PCR) analysis on peripheral blood mononuclear cells and granulocytes showed that the hADA-retrovirus was present in approximately 0.1% of the cells for at least 400 days post transplantation in 2 monkeys. Bone marrow that was harvested 16 months after transplantation carried ADA-overexpressing myeloid progenitor cells capable of in vitro colony formation. In addition, hADA activity could be demonstrated in T lymphocytes that were harvested 9 months post transplantation. Thus, in vitro transduction of CD34+CD11b- cells led to long-term repopulation of the hematopoietic system with transduced cells of lymphoid and myeloid lineages expressing the hADA gene. To investigate whether infusion of virus-producing cells into a rhesus monkey undergoing autologous bone marrow transplantation could lead to in vivo transfer of the recombinant retrovirus, 1 monkey was infused with CD34+CD11b- bone marrow cells (BMC) and a large quantity of virus-producing cells. Few provirus-carrying cells could temporarily be detected in this animal. This shows that in vivo gene transfer into a regenerating hemopoietic system can occur, albeit at very low efficiency.
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PMID:Gene transfer into nonhuman primate CD34+CD11b- bone marrow progenitor cells capable of repopulating lymphoid and myeloid lineages. 751 88

Previous studies in which an isolated heart or in situ constant pressure preparation was used suggested a minimal role for adenosine in autoregulatory control of coronary circulation. These results, however, are controversial, and the role of adenosine in autoregulation of flow in heart is uncertain. To test the hypothesis that adenosine mediates microvascular dilation in response to reduction in perfusion pressure (PP), we performed experiments in 41 open-chest chloralose-anesthetized dogs. Internal diameters (ID) of epicardial small arterioles < 100 mumol were measured with an intravital microscope and stroboscopic epiillumination synchronized to cardiac cycle. PP was reduced by graded stenoses of the left anterior descending coronary artery (LAD, mild stenosis PP = 60 mm Hg; critical stenosis PP = 40 mm Hg) and complete occlusion. 8-Phenyltheophylline (8-PT 10 microM) or adenosine deaminase (ADA 10 U/min) was topically superfused onto the heart. Arteriolar dilation induced by topically applied adenosine < or = 10 microM was completely blocked by 8-PT. Without 8-PT (vehicle group), mild critical stenosis and complete occlusion caused arteriolar dilation (percentage of change in diameter 8.6 +/- 2.6, 16.0 +/- 2.7, and 13.6 +/- 4.8%). 8-PT did not inhibit this dilation (8.5 +/- 2.8, 16.1 +/- 4.6, 15.1 +/- 5.7%, NS vs. vehicle group). Topically applied ADA significantly inhibited intravenously (i.v.) administered adenosine-induced arteriolar dilation. Without ADA, arteriolar dilation occurred (16.6 +/- 3.0, 28.2 +/- 4.3, 15.4 +/- 6.2%, at each PP). However, ADA did not inhibit dilation induced by gradual stenoses (10.6 +/- 1.4, 24.2 +/- 4.3, 17.5 +/- 6.9%, at each PP, NS vs. vehicle group).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of adenosine in vasodilation of epimyocardial coronary microvessels during reduction in perfusion pressure. 752

Human CD26, a Type II membrane glycoprotein with intrinsic dipeptidylpeptidase IV (DPPIV) activity and ability to bind adenosine deaminase type I (ADA-1), is expressed on epithelial cells constitutively, but on T lymphocytes its expression is regulated. A soluble form of CD26/DPPIV has been described in plasma and related to immunological status, but it has been defined by the presence of DPPIV activity rather than by isolation. Using nondenaturing chromatographic techniques followed by nondenaturing native preparative electrophoresis, we obtained a homogeneous preparation of soluble serum DPPIV and compared it with a recombinant soluble CD26/DPPIV (rsCD26). We show that serum DPPIV is a monomer of 175 kDa in contrast to rsCD26 of 105-110 kDa, that it exists as a trimer, and that it is probably a serine proteinase. Deglycosylation removed N-linked sugar from both serum DPPIV and rsCD26; no O-linked glycosylation was observed, revealing a protein core of 130 kDa for serum DPPIV. The large serum form expresses functional DPPIV activity with substrate and inhibitor specificities and pH activity profile similar to those of rsCD26. Epitope analysis showed that monoclonal antibodies against five epitopes expressed by rsCD26 also bound, but more weakly, with serum DPPIV. Analysis of peptides after limiting proteolysis and N-terminal sequences reveals no homology with rsCD26 but some identity with other peptidases. Unlike rsCD26, the serum form does not bind ADA-1 and has no ADA-1 already associated with it. Similarly to rsCD26, serum DPPIV is a potent T cell costimulator. We conclude that the serum form of DPPIV is unique and is not a breakdown product of membrane CD26. The conservation of DPPIV activity and five epitopes specific to rsCD26 suggest, however, a significant structural similarity.
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PMID:A novel form of dipeptidylpeptidase IV found in human serum. Isolation, characterization, and comparison with T lymphocyte membrane dipeptidylpeptidase IV (CD26). 753 99


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