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)

All of the superoxide dismutase isozymes of Escherichia coli have been shown to occur in the cell matrix, and none have been found in the periplasm. This was the case with both E. coli B and E. coli K-12, whether grown on a low phosphate medium or on a Trypticase soy-yeast extract medium. Alkaline phosphatase was used as a marker of the periplasm; adenosine deaminase and glucose 6-phosphate dehydrogenase were used as matrix markers, and consistent results were obtained by osmotic shock, spheroplast formation, and use of a diazonium salt that penetrates the periplasm but cannot cross the plasma membrane. A previous report that the iron-containing superoxide dismutase of E. coli is a periplasmic enzyme is now seen to have been in error.
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PMID:Intracellular localization of the superoxide dismutases of Escherichia coli: a reevaluation. 33 Apr 99

Eighty-three children with Down syndrome were submitted to hematological and biochemical studies; 69 normal children were included as controls. The variables analyzed were: HbF, HbA2, serum B12 vitamin (B12), folates, total iron and iron binding capacity, hematic cytology, and the red blood cell enzymes adenosine deaminase (ADA), glucose-6-phosphate dehydrogenase (G6PD) and superoxide dismutase (SOD). The most relevant results were: macrocytosis, normal leucocytes, HbF, B12 and folates, as well as high levels of the enzymes ADA and G6PD. An indirect association between macrocytosis, ADA and G6PD is discussed.
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PMID:Hematological and biochemical studies in children with Down syndrome. 170 Jun 61

Cyclic AMP accumulation in brain slices incubated with adenosine or the adenosine analogue 2-chloroadenosine was examined in different areas of rat cerebral cortex following a unilateral injection of FeCl2 solution into the sensorimotor cortex to induce chronic epileptic activity. In the epileptic cortex, cyclic AMP accumulation in cortical slices was elicited three- to 11-fold by adenosine. The elicitation by adenosine of cyclic AMP accumulation was markedly inhibited by the adenosine antagonist 8-phenyltheophylline. In anterior cortical areas of rats in which the appearance of electrographic isolated spikes was dominant either ipsilateral or contralateral to the injection site 8 days or more after the injection, the adenosine-elicited accumulation of cyclic AMP was greater on the side of dominant spike activity than on the other. In anterior cortical areas of rats showing nearly equal spike activity on the two sides 19 days or more after the injection, the cyclic AMP accumulation was greater on the side ipsilateral to the injection site than on the other. In anterior and posterior cortical areas of rats showing spike-and-wave complexes and isolated spikes 1 month or more after the injection, the cyclic AMP accumulation was greater on the ipsilateral side than on the other. Similar regional differences in the adenosine-elicited accumulation of cyclic AMP were detected in the presence of the adenosine uptake inhibitor dipyridamole or the phosphodiesterase inhibitor DL-4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 20-1724). The cyclic AMP accumulation was elicited five- to 17-fold by 2-chloroadenosine, in which case the elicitation was markedly inhibited by 8-phenyltheophylline. Regional differences in the 2-chloroadenosine-elicited accumulation of cyclic AMP were similar to those with adenosine and were detected in the presence of Ro 20-1724 or adenosine deaminase. The regional differences which correlated with the electrographic discharge patterns were due mainly to persistent changes in cyclic AMP accumulation on the primary epileptic side. These results suggest that alterations in adenosine-sensitive cyclic AMP generation in the cortex are associated with the neurochemical process leading to chronic iron-induced epilepsy.
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PMID:Regional difference in responsiveness of adenosine-sensitive cyclic AMP-generating systems in chronic epileptic cerebral cortex of the rat. 216 35

H2O2-mediated cytotoxicity (as measured by 51Cr-release) of rat pulmonary artery endothelial cells was time-dependent and related to the concentration of H2O2 employed. The cytotoxic effects of H2O2 were, as expected, prevented by catalase and the degree of protection was directly related to its time of addition. Endothelial cells were incubated with [14C]adenosine to achieve intracellular labeling of ATP, after which the cells were exposed to H2O2. Based on analysis of cell extracts by high-performance liquid chromatography, there was a time-dependent loss of intracellular radioactivity and ATP with the simultaneous appearance of purine degradation products including xanthine/hypoxanthine. Approximately 50% of the intracellular ATP was lost after 15 minutes of exposure and up to 80% was lost by 30 minutes. The extracellular fluid of cells exposed to H2O2 contained significant amounts of xanthine/hypoxanthine. The ferric iron chelator deferoxamine provided almost complete protection against H2O2-mediated cytotoxicity. Two inhibitors of xanthine oxidase, allopurinol and oxypurinol, were also protective as was deoxycoformycin, an inhibitor of adenosine deaminase. Remarkably, cells protected by these agents showed the same loss of intracellular ATP as unprotected, H2O2-treated cells. These findings demonstrate the dissociation between ATP loss per se and oxidant injury of endothelial cells. ATP breakdown may be an important event leading to cellular injury in that this results in the formation of substrate for xanthine oxidase.
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PMID:H2O2-mediated cytotoxicity of rat pulmonary endothelial cells. Changes in adenosine triphosphate and purine products and effects of protective interventions. 217 53

Models of rats with iron deficiency anemia (IDA) were established, and changes in development of the thymus and spleen and adenosine deaminase (ADA) activity in them studied. The size and weight of the thymus in IDA rats were decreased, which suggested that the development of the thymus was lowered; but the size and weight of the spleen in IDA group were increased. ADA activities of the thymus and the spleen in IDA rats were significantly decreased by 32.98% and 25.89%, respectively. One week after iron supplement, the weight of the thymus and spleen in IDS group returned to normal level (P greater than 0.05), and their ADA activity also significantly increased, but ADA activity of the thymus tissue did not return to the normal. The results suggested that the changes in ADA activity of the thymus and spleen tissues were related to iron deficiency. Stepwise regression analysis suggested that there was a negative correlation between ADA activity of the thymus tissue and FEP/Hb ratio.
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PMID:[Influence of iron deficiency anemia on development of thymus and spleen and adenosine deaminase activity in rats]. 236 44

Administration of 2,3-dihydro-1H-pyrazole[2,3a]imidazole (IMPY, 150 mg/kg) followed 8 hr later by injection of deoxyadenosine/erythro-9-(2-hydroxyl-3-nonyl)adenine (dAdo/EHNA, 175 mg/17.5 mg/kg) on days 2, 3, 6, and 7 increased the mean survival time of L1210 tumor bearing mice (210%). The sequential treatment was more efficacious than the simultaneous administration of these drugs. Administration of IMPY or dAdo/EHNA, alone, at the same doses as in the combination, did not prolong the life-span of tumor bearing mice. To determine the basis for the increased survival due to the sequential treatment with IMPY and dAdo/EHNA, cell cycle analysis and deoxyribonucleoside triphosphate concentrations were measured. Cytotoxicity of IMPY and dAdo/EHNA is known to be achieved through the inhibition of ribonucleotide reductase. IMPY is a specific inhibitor of the nonheme-iron subunit of ribonucleotide reductase, whereas deoxyadenosine in the presence of the adenosine deaminase inhibition, EHNA, is converted to deoxyadenosine 5'-triphosphate (dATP), which is a specific inhibitor of the effector-binding-subunit of ribonucleotide reductase. Our studies showed that L1210 cells accumulated in early S-phase, whereas intracellular dATP and deoxyguanosine triphosphate (dGTP) pools were depleted 8 hr after IMPY administration. dAdo/EHNA administration 8 hr after IMPY injection caused an increase in the intracellular concentration of dATP while maintaining the depletion of the dGTP pool and prolonged the S-phase as compared to the administration of IMPY alone.
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PMID:Antineoplastic effect of the combination of 2,3-dihydro-1H-pyrazole[2,3a]imidazole plus deoxyadenosine/erythro-9-(2-hydroxyl-3-nonyl)adenine in mice with L1210 leukemia cells. 236 48

Eight autopsies of patients with adenosine deaminase deficient-severe combined immunodeficiency disease (ADA-SCID) were reviewed with special emphasis on the lymphoid tissues. The thymus histology in five cases was remarkably uniform, whether or not prior ADA enzyme replacement or immunologic reconstitution therapy had been administered. Lymph nodes and spleens in all cases examined showed a residual nonlymphoid architectural framework corresponding to usual T and B cell zones found in normals. The development of an extranodal, monoclonal IgA lambda B cell immunoblastic lymphoma as a terminal event in one patient after several years of successful ADA enzyme replacement therapy through multiple red blood cell transfusions is described. In another patient with long-term ADA enzyme replacement, a terminal autoimmune hemolytic anemia developed. Autopsy revealed severe deposits of iron in the B cell zones of the lymph nodes, which is an unusual location. In addition, iron deposits outlined the splenic trabeculae, as well as the ring fibers and bridging fibers of the splenic sinuses.
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PMID:Pathologic findings in adenosine deaminase deficient-severe combined immunodeficiency. II. Thymus, spleen, lymph node, and gastrointestinal tract lymphoid tissue alterations. 259 74

Diamond-Blackfan anemia (DBA) is manifested by a wide variety of clinical and in vitro abnormalities. Despite this biological diversity, the hematological phenotype is remarkably similar for all patients and consists of a normochromic-macrocytic anemia in early childhood, reticulocytopenia, and a normocellular marrow with a selective deficiency of red cell precursors. Fetal hemoglobin is usually increased, distributed heterogeneously, has a fetal G gamma/A gamma pattern, and is associated with increased expression of red cell i antigen. Although most cases are sporadic, there are examples of autosomal recessive and autosomal dominant inheritance patterns. Approximately 70% of patients with DBA respond to prednisone, and many can be maintained on tapered doses. Those who are steroid-dependent at high dosage as well as those who do not respond are managed on a transfusion and iron chelation program. Claims of efficacy for other therapies, such as cyclosporine or high-dose intravenous methylprednisolone, require substantiation. Bone marrow transplantation has been successfully performed in patients who have tissue-matched donors, and the procedure cures the anemia. Recombinant growth factors may be a therapy of the future. Regarding pathophysiology, initial reports of humoral or cellular inhibitors of erythropoiesis were not confirmed in all laboratories. However, some patients have lymphocyte dysfunction with decreased T cells, decreased T4/T8 ratios, and defective lymphocyte-mediated suppression of lymphoproliferation. A large body of data indicates that the erythroid stem cells are intrinsically defective in DBA, and they are partly or completely refractory to erythropoietin. The role of elevated red cell adenosine deaminase activity in the pathogenesis of this abnormal erythropoiesis is not clear, but this finding is characteristic of the syndrome in most patients. Present studies using recombinant growth factors have demonstrated a diversity of defects in erythropoiesis in patients with DBA. Blocks in red cell production and red cell maturation were seen at various levels along the differentiation pathway. Of clinical interest, interleukin-3 has a corrective effect in vitro on the aberrant marrow erythropoiesis of steroid-refractory patients, and, hence, it may have therapeutic application.
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PMID:Diamond-blackfan anemia: etiology, pathophysiology, and treatment. 269 54

Oxidative stress and adenine nucleotide catabolism occur concomitantly in several disease states, such as cardiac ischaemia-reperfusion, and may act as synergistic determinants of tissue injury. However, the mechanisms underlying this potential interaction remain ill-defined. We examined the influence of oxidative stress on the molecular, kinetic and regulatory properties of a ubiquitous AMP-catabolizing enzyme, adenylate deaminase (AMPD) (EC 3.5.4.6). To this intent, rabbit heart AMPD and an H2O2/ascorbate/iron oxidation system were employed. Enzyme exposure to the complete oxidation system acutely impaired its catalytic activity, lowered the Vmax. by 7-fold within 5 min, and rendered the enzyme unresponsive to nucleotide effectors. Irreversible AMPD inactivation resulted within about 15 min of oxidative insult and was not prevented by free-radical scavengers. Oxidative stress did not affect the molecular mass, tetrameric nature, Km, immunoreactivity or trypsinolytic pattern of the enzyme; nor did it induce carbonyl formation, Zn2+ release from the holoenzyme or net AMPD S-thiolation. This injury pattern is inconsistent with a radical-fragmentation mechanism as the basis for the oxidative AMPD inactivation observed. Rather, the sensitivity of the enzyme to both S-thiolation and thiol alkylation and the significant (3 of 9/mol of denatured enzyme) net loss of DTNB-reactive thiols on exposure to oxidant strongly implicate the conversion of essential thiol moieties into stable higher-oxidation states in the oxidative inactivation of cardiac AMPD. The altered thiol status of the enzyme on oxidative insult may prohibit a catalytically permissible conformation and, in so doing, increase AMP availability to 5'-nucleotidase in vivo.
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PMID:Oxidative modulation and inactivation of rabbit cardiac adenylate deaminase. 788 95

The 2'-deoxy-2'-methylene derivatives of adenosine (MdAdo), guanosine (MdGuo), tubercidin (MdTu), cytidine (MdCyd) and uridine (MdUrd) were synthesized as mechanism-based inhibitors directed at ribonucleotide reductase. It was shown that MdCyd 5'-diphosphate irreversibly inactivated ribonucleotide reductase from Escherichia coli (Baker et al., J Med Chem 34: 1879-1884, 1991). In studies reported here, MdAdo/EHNA, MdGuo and MdCyd inhibited L1210 cell growth with IC50 values of 3.4, 10.6 and 1.4 microM, respectively. Since MdAdo is a substrate for adenosine deaminase, the presence of EHNA was required to give maximal growth inhibition. 8-Aminoguanosine was not required to maximize the cytotoxic effects of MdGuo. The 2'-deoxy-2'-methylene derivatives of tubercidin and uridine did not inhibit L1210 cell growth at concentrations as high as 50 microM (MdTu) or 100 microM (MdUrd). L1210 cell lines resistant to hydroxyurea (directed at the non-heme iron subunit of ribonucleotide reductase) or deoxyadenosine (directed at the effector binding subunit of ribonucleotide reductase) were not resistant to MdCyd. An L1210 cell line that was highly resistant to dGuo due to the loss of a relatively specific deoxyribonucleoside kinase (Cory et al., J Biol Chem 268: 405-409, 1993) had a 6.6-fold increase in the IC50 value toward MdCyd, but showed only a 2-fold increase in resistance to MdGuo. Another L1210 cell line that was markedly deficient in adenosine kinase activity was highly resistant to MdAdo. Analysis by flow cytometry showed that MdCyd showed the transit of the cells through the G2/M phase of the cell cycle resulting in the buildup of the G2/M population. MdAdo, MdGuo and MdCyd inhibited the incorporation of [14C]cytidine into DNA without an effect on RNA synthesis or total cellular uptake of [14C]cytidine. The conversion of [14C]cytidine to deoxycytidine nucleotides was partially inhibited by MdGuo, but not by MdAdo or MdCyd. These data show that the 2'-deoxy-2'-methylene derivatives of adenosine, guanosine and cytidine are activated via specific nucleoside kinases and that the modes of action of these compounds are not identical.
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PMID:2'-Deoxy-2'-methylene derivatives of adenosine, guanosine, tubercidin, cytidine and uridine as inhibitors of L1210 cell growth in culture. 830 81


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