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)

In 32PO4-labeled adipocytes, isoproterenol (ISO) or physiologically relevant concentrations of insulin rapidly increased phosphorylation of a particulate 135-kDa protein which has been identified as a cGMP-inhibited "low Km" cAMP phosphodiesterase (CGI-PDE) by several criteria, including selective immunoprecipitation with anti-CGI-PDE IgG (Degerman, E., Smith, C.J., Tornqvist, H., Vasta, V., Belfrage, P., and Manganiello, V.C. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 533-537). The time courses and concentration dependences for phosphorylation of CGI-PDE by ISO and insulin correlated with CGI-PDE activation in the presence of these agents; effects of ISO were somewhat more rapid than those of insulin. Adenosine deaminase, which metabolizes the adenylate cyclase inhibitor adenosine, also rapidly induced phosphorylation and activation of CGI-PDE. Phenylisopropyladenosine (an adenosine deaminase-resistant adenosine analog) prevented or reversed both adenosine deaminase-stimulated phosphorylation and activation of CGI-PDE (IC50 approximately 0.2 nM). Incubation of adipocytes with 0.1 nM insulin in the presence of ISO rapidly produced 30-200% greater activation and phosphorylation of CGI-PDE than the expected added effects of insulin and ISO individually; both effects preceded the insulin-induced decreases in protein kinase A activity and inhibition of lipolysis. These and other results indicate that CGI-PDE can be phosphorylated at distinct sites and activated by cAMP-dependent and insulin-dependent serine kinase(s), that the activation state of CGI-PDE reflects its relative phosphorylation state, and that synergistic phosphorylation/activation of CGI-PDE may be important in the antilipolytic action of insulin.
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PMID:Hormone-sensitive cyclic GMP-inhibited cyclic AMP phosphodiesterase in rat adipocytes. Regulation of insulin- and cAMP-dependent activation by phosphorylation. 164 89

The mechanism by which hyperglycaemia causes decreased (Na+,K+)-ATPase activity preventable by aldose reductase inhibitors and by raising plasma myo-inositol in specific tissues can be activated in vitro in normal rabbit aortic wall; it selectively inhibits a component of resting (Na+,K+)-ATPase activity maintained by a novel regulatory system through rapid basal phosphatidylinositol turnover (hydrolysis) in a discrete pool, which is replenished by a fraction of phosphatidylinositol synthesis that selectively requires myo-inositol transport. A role for endogenously released adenosine in this regulatory system was examined. Adding adenosine deaminase or 8-phenyltheophylline, an adenosine receptor antagonist, selectively inhibited the component of (Na+,K+)-ATPase activity maintained by the regulatory system; when inhibited with adenosine deaminase this component was restored by 2-chloroadenosine, 5'-N-ethylcarbox-amidoadenosine, and 1-oleoyl-2-acetylglycerol, but not by forskolin (which also did not inhibit this component). Adenosine deaminase inhibited the rapid basal turnover of the discrete phosphatidylinositol pool, and 2-chloroadenosine then stimulated its turnover. Raising medium glucose from 5 to 10-30 mmol/l inhibits the regulatory system by making myo-inositol transport at a normal plasma level inadequate to maintain the replenishment of the discrete phosphatidylinositol pool. 2-Chloroadenosine stimulation of the "adenosine-sensitive" component of (Na+,K+)-ATPase activity was inhibited in tissue incubated with 30 mmol/l glucose and myo-inositol in a normal plasma level, but this effect was demonstrable when the medium myo-inositol was raised seven-fold. Hyperglycaemia-induced decreased (Na+,K+)-ATPase activity that is preventable by aldose reductase inhibitors and by raising plasma myo-inositol results from the inhibition of a novel adenosine-(Na+,K+)-ATPase regulatory system.
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PMID:Elevated extracellular glucose inhibits an adenosine-(Na+,K+)-ATPase regulatory system in rabbit aortic wall. 165 55

We have identified a previously unrecognized missense mutation in a patient with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). The mutation is a G646-to-A transition at a CG dinucleotide and predicts a glycine-to-arginine substitution at codon 216. Computer analysis of secondary structure predicts a major alteration with loss of a beta-pleated sheet in a highly conserved region of the protein. The basepair substitution also generates a new site for the restriction enzyme BstXI in exon 7 of the genomic DNA. Digestion of genomic DNA from the patient and from his parents revealed that he was homozygous for the mutation and that his mother and father were carriers. This mutation in homozygous form appears to be associated with very severe disease, since the patient had perinatal onset of clinical manifestations of SCID, the highest concentration of the toxic metabolite deoxyATP in nine patients studied, and a relatively poor immunologic response during the initial 2 years of therapy with polyethylene glycol-adenosine deaminase. Analysis of DNA from 21 additional patients with ADA-SCID and from 19 unrelated normals revealed that, while none of the normal individuals showed the abnormal restriction fragment, two of the 21 patients studied were heterozygous for the G646-to-A mutation.
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PMID:Homozygosity for a newly identified missense mutation in a patient with very severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). 168 Feb 89

The distribution of adenosine deaminase and adenosine deaminase complexing protein in rabbit heart has been compared using immunohistochemical staining procedures. Sections (4-5 microns) of tissue fixed in Clarke's solution or paraformaldehyde and embedded in paraffin were stained by the peroxidase anti-peroxidase method for adenosine deaminase or complexing protein, using affinity purified antibodies. Staining for adenosine deaminase and complexing protein was observed in the central myocardium of all heart chambers. Adenosine deaminase was detected in endothelial cells of blood vessels and adjacent pericytes. The nuclei of arteries stained heavily for adenosine deaminase, whereas those of venules and small veins, although positive, stained much more lightly. The cytoplasm of blood vessel endothelial cells and smooth muscle cells of the tunica media were also weakly positive for adenosine deaminase. Endothelial cells of the endocardium and epicardium did not stain. Randomly distributed mononuclear inflammatory cells and interstitial connective tissue fibroblasts were also negative for adenosine deaminase. These results raise the possibility that endothelial cells containing adenosine deaminase could serve as a metabolic barrier preventing the free exchange of plasma and interstitial adenosine. Positive staining for complexing protein was restricted to blood vessel endothelial cells, especially cytoplasmic processes. Colocalization experiments carried out with biotinylated primary antibodies indicate that some vessels are positive for both adenosine deaminase and complexing protein. This is the first experimental evidence of possible in situ association of adenosine deaminase and complexing protein.
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PMID:Localization of adenosine deaminase and adenosine deaminase complexing protein in rabbit heart. Implications for adenosine metabolism. 168 16

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

Amphotropic helper-free retrovirus vectors containing the bacterial neomycin phosphotransferase gene (neo) and the human adenosine deaminase gene (adenosine aminohydrolase, EC 3.5.4.4; ADA) were used to transduce canine marrow cells. In one approach, dogs were treated for 7 days with recombinant human granulocyte colony-stimulating factor to stimulate hematopoietic cell division. Bone marrow cells were collected and transduced by 24 hours of cocultivation on vector-producing cells followed by incubation in a vector-containing long-term marrow culture system for 4 days. Transduced autologous marrow (0.4 to 1.0 x 10(8) cells/kg) was infused into dogs administered otherwise lethal total body irradiation (TBI) of 920 cGy. Two of four dogs engrafted, and their marrows showed intermittently between 1% and 11% G418-resistant colony-forming unit granulocyte-macrophage (CFU-GM) colonies for up to 2 years after transplantation. In a different experimental approach, autologous marrow, obtained at the time of the PB neutrophil nadir 7 days after a single cyclophosphamide injection (40 mg/kg intravenously), was cocultivated for 24 hours on vector-producing cells and infused at doses of 0.06 to 0.18 x 10(8) cells/kg into dogs administered 920 cGy TBI. One of three dogs engrafted, and the marrow showed intermittently 1% to 10% G418-resistant CFU-GM colonies for at least 2 years. Culture results were confirmed by polymerase chain reaction (PCR) showing the presence of the neo gene in marrow cells, peripheral blood (PB) granulocytes, and PB and lymph node lymphocytes. Dilution experiments indicated that up to 10% of marrow, lymph node, and PB cells contained the neo gene, consistent with the culture results. Samples harboring the neo gene also contained the gene for human ADA. However, repeated analyses of PB and marrow cells for human ADA gene expression by starch gel electrophoresis were negative. PB samples of all dogs were free of helper virus, and no long-term side effects from the transduction were observed.
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PMID:Retrovirus-mediated gene transduction into long-term repopulating marrow cells of dogs. 172 5

Gene transfer into vascular smooth muscle cells in animals was examined by using recombinant retroviral vectors containing an Escherichia coli beta-galactosidase gene or a human adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) gene. Direct gene transfer by infusion of virus into rat carotid arteries was not observed. However, gene transfer by infection of smooth muscle cells in culture and seeding of the transduced cells onto arteries that had been denuded of endothelial cells was successful. Potentially therapeutic levels of human adenosine deaminase activity were detected over 6 months of observation, indicating the utility of vascular smooth muscle cells for gene therapy in humans.
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PMID:Long-term expression of human adenosine deaminase in vascular smooth muscle cells of rats: a model for gene therapy. 173 97

Adenosine deaminase (ADA) deficiency may manifest as severe combined immunodeficiency (SCID) in early infancy. Some of these children develop radiologic changes which may be in part related to effects of this enzyme deficiency on the bony epiphysis. We describe the radiologic changes in a neonate with ADA deficiency and their resolution with polyethylene glycol conjugated adenosine deaminase (PEG-ADA, ADAGEN: Enzon, Inc., South Plainfield, NJ) enzyme replacement therapy.
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PMID:Chondroosseous dysplasia in severe combined immunodeficiency due to adenosine deaminase deficiency (chondroosseous dysplasia in ADA deficiency SCID). 174 85

Adenosine deaminase activity was measured in cerebrospinal fluid of patients with confirmed tuberculous and bacterial meningitis. The values were compared with those of control subjects without meningitis. A statistically significant increase in the level of this enzyme was noted in the two types of meningitis, but no definite demarcation in the levels was observed between the two types. Therefore increases in adenosine deaminase activity may not be of such diagnostic significance as reported elsewhere.
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PMID:Adenosine deaminase levels in cerebrospinal fluid in tuberculosis and bacterial meningitis. 757 24

The value of ascites gamma interferon concentration and ascites adenosine deaminase activity in distinguishing tuberculosis from other causes of ascites was examined in a prospective study of 86 patients with ascites, including 16 with tuberculous peritonitis. Gamma interferon concentration was higher in tuberculous peritonitis than in the other causes of ascites (p less than 0.0001), and a cut-off between 3 and 9 u/ml reached a sensitivity and a specificity of 100%. The mean (+/- SD) gamma interferon level in tuberculous ascites was 39.3 +/- 18.3 u/ml in patients seronegative for HIV and 14.2 +/- 4.7 u/ml in patients with AIDS (p = 0.01). Adenosine deaminase activity in tuberculous ascites was also higher than in the other causes of ascites (p less than 0.0001), and a cut-off of 40 u/l reached a sensitivity of 100% and a specificity of 97%. The two false positives for adenosine deaminase test were true negatives for the gamma interferon test. There was no significant correlation between gamma interferon concentration and adenosine deaminase activity either in tuberculous ascitis or in any other group. This study suggests that ascites gamma interferon determination may be very useful in the screening of tuberculous peritonitis, but its cost makes it advisable to use adenosine deaminase activity as a routine test, at least in areas where tuberculosis is endemic.
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PMID:Diagnostic value of ascites gamma interferon levels in tuberculous peritonitis. Comparison with adenosine deaminase activity. 177 79


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