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)

The platelets of an infant with severe combined immune deficiency and adenosine deaminase deficiency showed markedly diminished responses to ADP-induced aggregation in vitro. This abnormality was corrected by the addition of purified adenosine deaminase in vitro. Exogenous adenosine added to platelet-rich plasma caused markedly prolonged inhibition of ADP-induced aggregation. This was shown by isotopic studies to be due to slow clearance of adenosine and hence persistence of this nucleoside. Direct assay for adenosine deaminiase in plasma and platelet lysates of the patient confirmed the very low activity of this enzyme. Raised cAMP levels were demonstrated in his platelets. The deranged adenosine metabolism and raised cAMP in the platelets of this child with severe combined immunodeficiency may explain the altered response to ADP. Despite the in vitro platelet aggregation abnormality, the patient had no clinical evidence of impaired hemostasis.
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PMID:In vitro platelet abnormality in adenosine deaminase deficiency and severe combined immunodeficiency. 21 40

Since extracellular adenosine is a physiologically important regulator of adenylate cyclase and cell function in various mammalian tissues, we have examined the effect of adenosine on histamine release from human basophils. Adenosine inhibited IgE-mediated histamine release by its ability to increase leukocyte cyclic AMP levels; the same concentrations of adenosine which inhibited histamine release increased the cyclic AMP level of mixed leukocytes. Inhibition of histamine release was also observed with an adenosine deaminase (ADA) inhibitor [erythro-9-(2-hydroxy-3-nonyl)-adenine: EHNA] in the presence of autologous serum. We suggest that the adenosine-ADA system normally modulates histamine release and that this contributes to the severe combined immune deficiency (SCID) associated with a lack of ADA.
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PMID:Adenosine-adenosine deaminase modulation of histamine release from human basophils in vitro. 22 78

A role for the enzymes adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) and purine-nucleoside phosphorylase (purine-nucleoside:orthophosphate ribosyl-transferase, EC 2.4.2.1) in the functional maturation of lymphoid cells has been revealed by the association of inherited deficiencies of these enzymes and profound immune deficiency. Previous studies have suggested that the selective toxicity for lymphocytes may be mediated by the accumulation of toxic deoxynucleoside metabolites, likely through the action of specific kinases enriched in lymphoid cells. In order to study possible mechanisms whereby lymphocyte function may be impaired in these disorders, we have studied the effect of nucleosides and their deoxy analogues on both T and B lymphocyte growth and function. In the presence of deoxyguanosine, there was marked inhibition of T lymphoblast growth, phytohem-agglutinin-induced cell proliferation, and T suppressor cell activity. T helper cell activity and the differentiation of B cells to an antibody-secreting stage were unaffected. Deoxyadenosine was much less inhibitory, but in the presence of an inhibitor of adenosine deaminase, its effects on lymphocyte growth and function were markedly potentiated. The addition of deoxycytidine prevented deoxyadenosine toxicity in all assays, whereas it only interfered with deoxyguanosine effects on T lymphoblast growth. These studies provide some initial understanding for the selective loss of specific lymphocyte functions in individuals with inborn errors of purine metabolism.
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PMID:Selective toxicity of purine deoxynucleosides for human lymphocyte growth and function. 31 53

In spite of the numerous theories proposed to explain the origin of the diversity of immunoglobulins, none can define satisfactorily the nature of the generator of diversity and its mode of action. Even the concept of the variable and constant portions of immunoglobulin chains is no longer valid which opens up the question about the hypothetical existence of the V and C genes. Moreover, phylogenetic considerations strongly suggest that there is a fundamental difference in the mechanism of amino acid substitution for the immunoglobulins and for homologous proteins undergoing normal divergent evolution. A conceptionally and functionally simple mechanism, based on a variable translation of the immunoglobulin mRNA, has been suggested as the generator of diversity (Rev. canad. Biol., 1969, 28, 179). The criteria of this mechanism are (1) the presence of inosine in the mRNA and (2) the existence of a series of overmethylated tRNAs for the selective recognition of inosine-containing codons. Although the experimental proof for this mechanism is still lacking, it cannot be fortuitous that the lack of adenosine deaminase is associated with immune deficiency and that an increased tRNA methylase activity exists in plasmocytomas.
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PMID:[Considerations on the origin of the diversity of immunoglobulins (author's transl)]. 84 93

Purine and pyrimidine metabolites were measured in erythrocytes, plasma, and urine of a 5-month-old infant with adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) deficiency. Adenosine and adenine were measured using newly devised ion exchange separation techniques and a sensitive fluorescence assay. Plasma adenosine levels were increased, whereas adenosine was normal in erythrocytes and not detectable in urine. Increased amounts of adenine were found in erythrocytes and urine as well as in the plasma. Erythrocyte adenosine 5'-monophosphate and adenosine diphosphate concentrations were normal, but adenosine triphosphate content was greatly elevated. Because of the possibility of pyrimidine starvation, pyrimidine nucleotides (pyrimidine coenzymes) in erythrocytes and orotic acid in urine were measured. Pyrimidine nucleotide concentrations were normal, while orotic acid was not detected. These studies suggest that the immune deficiency associated with adenosine deaminase deficiency may be related to increased amounts of adenine, adenosine, or adenine nucleotides.
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PMID:Purine metabolism in adenosine deaminase deficiency. 106 99

The recently discovered association of adenosine deaminase (ADA) deficiency and combined immune deficiency (CID) has emphasized the critical role of purine salvage in the function of lymphoid tissue. Known enzymatic properties of ADA are presented. In addition, known phenotypic data and possible genetic mechanisms for the occurrence of ADA deficiency in CID are discussed. A hypothesis based on considerations of known metabolic pathways in human erythrocytes is proposed to account for the selectivity of ADA deficiency for lymphoid tissue. Finally, some inhibitors of ADA are discussed as well as some immunosuppressive agents.
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PMID:Combined immunodeficiency disease: an inborn error of purine metabolism. 114 76

Recently, we investigated a Belgian patient with severe combined immune deficiency caused by a dysfunction of the gene for adenosine deaminase (ADA-SCID), which was found to be due to a 3.2-kb deletion spanning the promoter and the first exon of the ADA gene (Berkvens et al., 1987, Eur. J. Pediatr. 146:329). No ADA-specific RNA could be detected in primary fibroblasts derived from this patient. In the present paper we establish via direct sequencing of in vitro amplified DNA that the 3250-bp deletion is due to a recombination within the left arms of two direct AluI repeats. This mutation is identical to one reported for an unrelated patient in the United States (Markert et al., 1988, J. Clin. Invest. 81:1323-1327).
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PMID:Identical 3250-bp deletion between two AluI repeats in the ADA genes of unrelated ADA-SCID patients. 169 26

Certain disorders of the immune system seem to be associated with skeletal defects. The association was first recorded by McKusick et al. (Bulletin of the Johns Hopkins Hospital 116:285-326, 1964). A number of relationships between lymphocytes and osteocytes can be proposed. These include a common environment for development, common metabolic needs and effects upon osteocytes by products (cytokines) elaborated from lymphocytes or monocytes during immune responses. Thus, bony defects of varying degrees of severity are seen in short-limb dwarfs, cartilage-hair hypoplasia, and adenosine deaminase (ADA) deficiency. Cytokine activation of osteoclasts accounts for the lytic lesions seen in malignancies and the excessive bone resorption which accompanies autoimmune disorders such as rheumatoid arthritis. Correction of primary immune deficiency is accomplished by bone marrow transplantation. If the bony abnormality is subtle (as in some cases of ADA deficiency) the skeletal problem is resolved; if the bone defect is major as in short-limb dwarfism, no improvement is seen.
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PMID:Associations of the skeletal and immune systems. 268 81

The gene for human adenosine deaminase (ADA), an enzyme constitutively expressed in all tissues investigated so far and deficient in some cases of severe combined immune deficiency, was previously assigned to chromosome 20 by syntenic analysis, using somatic cell hybrids and quantitative enzyme studies on patients with chromosome abnormalities. Attempts at regional localization of ADA through indirect approaches have so far resulted in uncertainties, as well as apparent inconsistencies. In situ hybridization of high-resolution somatic and pachytene chromosomes using a 3H-labeled cDNA probe of the ADA gene localized the gene to 20q12----q13.11. Rearrangements involving this region have been reported in various human hematological malignancies; in this regard, possible implications of the physical proximity of the ADA gene locus to that of SRC, an oncogene previously localized to the same region of chromosome 20, are briefly discussed.
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PMID:Localization of human adenosine deaminase (ADA) gene sequences to the q12----q13.11 region of chromosome 20 by in situ hybridization. 277 85

Acquired immunodeficiency syndrome (AIDS) is an often fatal disease caused by a retrovirus frequently resulting in malignancy and/or opportunistic infection. Because the immune deficiency in AIDS is similar to that in some purine enzyme deficiencies, we measured erythrocyte adenosine deaminase (ADA) and purine nucleoside phosphorylase activities in patients with AIDS, heterosexual controls, and a high-risk asymptomatic population. We found that erythrocyte ADA activity was significantly elevated in patients with AIDS (40 +/- 11 nmol/mg of hemoglobin per hr, mean +/- SD) relative to heterosexual controls (25 +/- 10, P less than 0.001). We also measured ADA activity in a group of individuals at high risk for AIDS and found that approximately half had significantly elevated ADA activities (45 +/- 4, P less than 0.002) that correlated with the presence of antibody to the lymphadenopathy retrovirus. Purine nucleoside phosphorylase activity was relatively normal in patients with AIDS as well as in individuals at risk for AIDS. Increased ADA appears to be a diagnostic marker of AIDS and may be useful in conjunction with antibody to the AIDS-related retrovirus in detecting the presence of infection in asymptomatic high-risk individuals. These data also suggest that, in addition to the lymphocyte, the erythroid cell line may also be infected by the AIDS-related retrovirus.
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PMID:Elevated erythrocyte adenosine deaminase activity in patients with acquired immunodeficiency syndrome. 300 27


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