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)

Purine metabolism and phosphoribosylpyrophosphate content of lymphocytes and erythrocytes were studied in an immunocompetent black male child with a total deficiency of erythrocyte and partial deficiency of lymphocyte adenosine deaminase. The partial genetic deficiency of adenosine deaminase was demonstrated in intact lymphocytes, and was approximately one third of the deaminating activity of control lymphocytes. Intact lymphocytes of the patient did not incorporate adenosine at a faster rate than those of control lymphocytes. The patient's erythrocytes deaminating activity was low and adenine ribonucleotide synthesis from adenosine was increased several fold, while adenine incorporation into purine ribonucleotides was comparable to that of control erythrocytes. Transfusion with packed erythrocytes temporarily improved the deaminating capacity of circulating erythrocytes, but did not reduce the elevated incorporation of adenosine into purine ribonucleotides. Phosphoribosylpyrophosphate content of the patient's lymphocytes and erythrocytes was not diminished. Incubation of erythrocytes with adenosine lowered phosphoribosylpyrophosphate content while incubation with phosphate increased phosphoribosylpyrophosphate content to the same extent in mutant and control erythrocytes.
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PMID:Purine and phosphoribosylpyrophosphate metabolism of lymphocytes and erythrocytes of an adenosine deaminase deficient immunocompetent child. 47 97

A procedure for isolation of adenylate deaminase from duck heart muscle has been developed. The method includes extraction of enzyme, chromatography on cellulose phosphate, fractionation by ammonium sulfate, chromatography on Sephadex G-25 and ion-exchange chromatography on DEAE-cellulose. The enzyme was purified approximately 4000-fold with a yield of 25%. Electrophoresis in polyacrylamide gel revealed that the enzyme contains no proteins other than adenylate deaminase. The enzyme has a UV absorption spectrum typical for proteins which contain no nucleic acid impurities. Using sievorptive chromatography, it was shown that the myocardial extract contains two adenylate deaminase forms, which are tetramers with mol. weights of 190 000 and 240 000. The molecular weights of the subunits are 47 000 and 63 000, respectively. In the oligomeric form the enzyme is only detected at high enzyme concentrations and in the presence of large amounts of substrate.
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PMID:[Purification and some physico-chemical properties of myocardial adenylate deaminase]. 50 71

To elucidate the mode of action of hexobendine, its effects on some enzyme activities, the uptake of adenosine by rat erythrocytes and changes in the concentration of various myocardial substrates following induced hypoxia in rat were studied. Hexobendine had no effect on the in vitro activities of the adenosine degrading enzyme, adenosine deaminase and of the A-PRTase, HG-PRTase which are associated with the salvage pathways of purine biosyntheses. The uptake of adenosine by rat erythrocytes in vitro was inhibited considerably by hexobendine. Hypoxic states results in a significant decrease in creatine phosphate, ATP, glycogen and glucose contents, and increase in ADP, AMP, adenosine and lactate contents in rat myocardials. These alterations in cardiac metabolism induced by hypoxia were significantly improved by hexobendine given orally in doses of 10 approximately 100 mg/kg. Thus, hexobendine was shown to maintain the normal aerobic energy metabolism of the heart under states of hypoxia. In such states adenosine may be released from tissues and this increase in the available concentration of adenosine in plasma through inhibition of uptake by erythrocytes may be involved in the coronary vasodilating action of hexobendine.
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PMID:[Effects of hexobendine on adenosine metabolism and myocardial energy metabolism (author's transl)]. 74 50

Blood samples from 509 Macushi and 623 Wapishana Amerindians of of Northern Brazil and Southern Guyana have been analyzed with reference to the occurrence of rare variants and genetic polymorphisms of the following 25 systems: (i) Erythrocyte enzymes: acid phosphatase-1, adenosine deaminase, adenylate kinase-k, carbonic anhydrase-1, carbonic anhydrase-2, esterase A1,2,3, esterase D, galactose-1-phosphate uridyltransferase, isocitrate dehydrogenase, lactate dehydrogenase, malate dehydrogenase, nucleoside phosphorylase, peptidase A, peptidase B, phosphoglucomutase 1, phosphoglucomutase 2, phosphogluconate dehydrogenase, phosphohexoseisomerase, triosephosphate isomerase and (ii) Serum proteins: albumin, ceruloplasmin, haptoglobin, hemoglobin A2 and transferrin. Fifteen different rare variants were detected, involving 11 of these systems. In addition, a previously undescribed variant of ESA 1,2,3 which achieves polymorphic proportions in both these tribes is described. Excluding this variant, the frequency of rare variants is 1.1/1000 in 12510 determinations in the Macushi and 4.7/1000 in 15396 determinations in the Wapishana. The ESA 1,2,3 polymorphism was not observed in 382 Makiritare, 232 Yanomama, 146 Piaroa, 404 Cayapo, 190 Kraho and 112 Moro. Irregularities in the intratribal distribution of this polymorphism in the Macushi and Wapishana render a decision as to the tribe of origin impossible at present. Gene frequencies are also given for previously described polymorphisms of 5 systems: haptoglobin, phosphoglucomutase 1, erythrocyte acid phosphatase, esterase D, and galactose-1-phosphate-uridyl-transferase.
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PMID:Genetic studies of the Macushi and Wapishana Indians. I. Rare genetic variants and a "private polymorphism' of esterase A. 87 Apr 12

The triple combination of 2'-deoxycoformycin (2'-dCF), 9-beta-D-arabinofuranosyladenine 5'-phosphate, and 9-beta-D-arabinofuranosylcytosine was found to be very effective in the therapy of C57BL X DBA/2 F1 mice with intracerebral L1210. At the dosages and dosage scheduling used, the double combination of 2'-dCF and 9-beta-D-arabinofuranosyladenine 5'-phosphate gave minimal but significant increases in life-span. When 9-beta-D-arabinofuranosylcytosine was given at suboptimal dosage to mice with intracerebral L1210, the host toxicity caused by 2'-dCF and 9-beta-D-arabinofuranosyladenine 5'-phosphate in combination was decreased by a factor of 2, allowing a more prolonged therapy. "Cures" were obtained with the triple combination at dosages of 9-beta-D-arabinofuranosylcytosine that did not "cure". The supernatant adenosine deaminase from C57BL X DBA/2 F1 mouse brains was purified and the Ki for 2'-dCF using 9-beta-D-arabinofuranosyladenine as substrate was determined to be not more than 2 X 10(-11) M.
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PMID:Effects of 2'-deoxycoformycin, 9-beta-D-arabinofuranosyladenine 5'-phosphate, and 1-beta-D-arabinofuranosylcytosine triple combination therapy on intracerebral leukemia 1210. 88 74

Concanavalin A inhibits serum 5'-nucleotidase activity, without causing significant inhibition of alkaline phosphatase activity. This observation serves as the basis for a new method for assaying the 5'-nucleotidase activity in serum, which depends upon the difference between the enzymic hydrolysis of adenosine-5'-monophosphate in the presence and absence of concanavalin A. A denosine released by the 5'-nucleotidase reaction is deaminated by a coupled reaction with adenosine deaminase to liberate inosine and ammonia, and ammonia is measured colorimetrically by the Berthelot reaction. In sera from 40 healthy adult persons, 5'-nucleotidase activity averaged 6.4 U/liter (SD, +/-2.0; range, 3-12). In sera from 100 patients, measurements of 5'-nucleotidase activity by the new assay averaged 8% lower than by a generally accepted method in which phenyl phosphate is used to suppress hydrolysis of adenosine-5'-monophosphate by alkaline phosphatase activity. The clinical validy of the new assay was tested by measuring serum 5'-nucleotidase activities in rats with bile duct ligation and in rats treated with thioacetamide to induce hepatocellular injury.
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PMID:Inhibition by concanavalin A as the basis for a specific assay of serum 5'-nucleotidase activity. 92 81

2'-Deoxycoformycin (2'-dCF), a potent inhibitor of adenosine deaminase, was tested in combination with 9-beta-D-arabinofuranosyladenine (ara-A) and 9-beta-D-arabinofuranosyladenine 5'-formate for cytotoxic activity against mouse leukemia L1210 in culture. 2'-dCF, which alone had no activity, significantly enhanced cytostatic and cytotoxic activities of ara-A and its more soluble derivative, 9-beta-D-arabinofuranosyladenine 5'-formate; the latter 2 agents, when tested at equimolar concentrations, were equivalent in their effects on proliferation and viability. The therapeutic response of mice bearing the in vitro line of L1210 cells (L1210/C2) to combination therapy with 2'-dCF and 9-beta-D-arabinofuranosyladenine 5'-phosphate was comparable to that reported elsewhere for therapy of mice bearing the parent in vivo line. Continuous exposure of cultured L1210 cells to ara-A and 2'-dCF induced a prolonged period of unbalanced growth, characterized by inhibition of proliferation and DNA synthesis while RNA and protein synthesis continued; exposure periods in excess of a single population doubling were required to achieve significant cell kill. Potentiation of ara-A activity against the relatively insensitive mouse leukemia L1210 was attributed to increased stability of ara-A resulting from 2'-dCF inhibition of adenosine deaminase.
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PMID:Enhancement of 9-beta-d-arabinofuranosyladenine cytotoxicity to mouse leukemia L1210 in vitro by 2'-deoxycoformycin. 94 95

Deamination of many analogs of adenine nucleosides results in the loss of their chemotherapeutic efficacy. Two approaches have been used in this study to overcome this problem. First, some adenine nucleotides, which are resistant to mammalian adenosine deaminase, are more toxic to animal cells than are the respective nucleosides. For toxic to animal cells than are the respective nucleosides. For example, 9-beta-D-arabinofuranosyladenine 5'-phosphate, a molecule that penetrates the cell without degradation, has a more sustained toxicity against mouse fibroblasts (L-cells) than does 9-beta-D-arabinofuranosyladenine (ara-A). Furthermore, L-cells treated with 2',3'-dideoxyadenosine 5'-phosphate are extensively killed after 48 hr, whereas 2',3'-dideoxyadenosine is almost nontoxic to L-cells. Specific inhibition of adenosine deaminase by nontoxic concentrations of erythro-9-(2-hydroxy-3-nonyl)adenine greatly potentiates the biological activity of both ara-A and 3'-deoxyadenosine (cordycepin). Simultaneous administration of cytostatic concentrations of ara-A and the inhibitor of adenosine deaminase to L-cells killed greater than 99.9 percent of cells in 36 hr. A similar concentration of ara-A plus the deaminase inhibitor also markedly extended the mean survival of mice bearing Ehrlich ascites carcinoma as compared to ara-A alone. A cytostatic concentration of cordycepin 1 x 10-4 M), administered in the presence of deaminase inhibitor, killed greater than 99.9 percent of cultured L-cells in only 8 hr. During the latter incubation, accumulation of uridine in acid-insoluble material reached a maximum after 30 min, and incorporation of thymidine into acid-insoluble material was almost totally arrested after 2 hr.
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PMID:Two approaches that increase the activity of analogs of adenine nucleosides in animal cells. 107 75

Cell-free, dialyzed extracts from Azotobacter vinelandii rapidly dephosphorylate [U-14C]ATP to labeled ADP and AMP, which is then degraded to hypoxanthine, the end product of AMP catabolism under the experimental conditions which were used. The intermediates of the pathway from ATP to hypoxanthine have been identified by thin layer chromatography and quantitated by the 14-C content. The concentrations of intermediates present during the production of hypoxanthine are consistent with AMP nucleosidase being responsible for AMP degradation in these extracts. This result was confirmed in experiments which utilized rabbit antibody prepared against purified AMP nucleosidase. The antibody inhibited AMP nucleosidase activity in cell-free extracts but did not inhibit adenine demanase or adenosine deaminase from the same extracts. In the presence of antibody prepared against purified AMP nucleosidase, the dialyzed extracts showed a marked reduction in the production of hypoxanthine from ATP. Other enzymes which could be responsible theoretically for the conversion of AMP to hypoxanthine were not detected by standard assay procedures. These results are consistent with AMP degradation proceeding by way of AMP nucleosidase to yield adenine and ribose 5-phosphate. The adenine is then converted to hypoxanthine by adenine deaminase. Both of these enzymes were present in sufficient quantities to account for the observed rates of hypoxanthine formation. The rate of hypoxanthine formation decreases during the time course of the [U-14-C]ATP degradation experiments, even though the concentration of AMP remains high. This decrease in the rate of hypoxanthine formation as a function of time is attributed to the decreasing ATP and increasing P0-4 concentrations, since ATP is an activator of AMP nucleosidase and P0-4 is an inhibitor. These observations suggest that the in vivo activity of AMP nucleosidase could also be regulated by changes in the relative ratios of ATP:AMP:P0-4.
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PMID:The pathway of adenylate catabolism in Azotobacter vinelandii. Evidence for adenosine monophosphate nucleosidase as the regulatory enzyme. 116 48

1. The presence of adenosine receptors linked to adenylate cyclase activity and their functional role in calcium-evoked 5-hydroxytryptamine (5-HT) release was investigated in rat basophilic leukaemia (RBL) cells, a widely used model for studying the molecular mechanisms responsible for stimulus-secretion coupling. 2. In [3H]-5-HT-loaded cells triggered to release by the calcium ionophore A23187, a biphasic modulation of 5-HT secretion was induced by adenosine analogues, with inhibition of stimulated release at nM and potentiation at microM concentrations, suggesting the presence of adenosine receptor subtypes mediating opposite effects on calcium-dependent release. This was also confirmed by results obtained with other agents interfering with adenosine pharmacology, such as adenosine deaminase and the non-selective A1/A2 antagonist 8-phenyl-theophylline. 3. Similar biphasic dose-response curves were obtained with a variety of adenosine analogues on basal adenylate cyclase activity in RBL cells, with inhibition and stimulation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) production at nM and microM concentrations, respectively. The rank order of potency of adenosine analogues for inhibition and stimulation of adenylate cyclase activity and the involvement of G-proteins in modulation of cyclic AMP levels suggested the presence of cyclase-linked A1 high-affinity and A2-like low-affinity adenosine receptor subtypes. However, the atypical antagonism profile displayed by adenosine receptor xanthine antagonists on cyclase stimulation suggested that the A2-like receptor expressed by RBL cells might represent a novel cyclase-coupled A2 receptor subtype.4. Micromolar concentrations of adenosine analogues could also increase inositol phospholipid hydrolysis and inositol tris-phosphate formation in both unstimulated cells and in cells triggered to release by the calcium ionophore. The stimulation was constant, small and additive to that exerted by the calcium ionophore.5. It is concluded that RBL cells express both A1 and A2-like adenosine receptors which exert opposite effects on 5-HT release and intracellular cyclic AMP levels. However, besides modulation of cyclic AMP levels, additional transduction pathways, such as modulation of phospholipase C activity, may contribute to the release response evoked by adenosine analogues in this cell-line.
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PMID:Adenosine receptors in rat basophilic leukaemia cells: transductional mechanisms and effects on 5-hydroxytryptamine release. 131 28


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