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:3.5.4.4 (adenosine deaminase)
5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of red cell adenosine deaminase (ADA) overproduction associated with hereditary hemolytic anemia is reported here. This appears to be the second report. Proband is a 38-year-old Japanese male who had hemoglobin, 15.8 g/100 ml; reticulocyte count, 4.5%; serum indirect bilirubin, 4.9 mg/100 ml; 51Cr-labeled red cell half-life, 12 days; red cells showed moderate stomatocytosis. His red cell ADA activity showed 40-fold increase while that of the mother showed 4-fold increase. The mother was hematologically normal. The father had a normal enzyme activity. The proband and the mother showed slightly high serum uric acid levels. The proband's red cell showed: ATP, 628 nmoles/ml (normal, 1,010--1,550); adenine nucleotide pool, 46% of the normal mean; 2,3-diphosphoglycerate content, 3,782 nmoles/ml (normal 4,170--5,300); increased oxygen affinity of hemoglobin, P50 of intact erythrocytes being 21.8 mmHg (normal, 24.1--26.1). Red cell glycolytic intermediates in the proband were low in general, and the rate of lactate production was low. Kinetic studies using crude hemolysate revealed a normal Km for adenosine, normal electrophoretic mobility but slightly abnormal pH curve and slightly low utilization of 2-deoxyadenosine. The ADA activity of lymphocytes was nearly normal.
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PMID:A case of red-cell adenosine deaminase overproduction associated with hereditary hemolytic anemia found in Japan. 73 30

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 erythrocytes of 350 pigtailed macaques (Macaca nemestrina) were examined for electrophoretic variation of hemoglobin and 26 enzymes. Seven enzymes showed variation in more than 1% of individuals: phosphoglucose isomerase, phosphoglucomutase-1, soluble NADP-dependent isocitric dehydrogenase, peptidase A, peptidase C, 2,3-diphosphoglycerate mutase, and acid phosphatase. Variation with lesser frequency was found in soluble glutamic-oxalacetic transaminase, phosphoglycerate kinase, lactic dehydrogenase, and hemoglobin. Only eight samples were tested for esterase D, and one of these had a variant phenotype. Enzymes with no clear variation were adenylate kinase, adenosine deaminase, phosphofructokinase, hexokinase, pyruvate kinase, glyceraldehyde 3-phosphate dehydrogenase, aldolase, phosphoglycerate mutase, phosphopyruvate hydratase (enolase), phosphoglucomutase-3, and superoxide dismutase. There was father-to-son transmission of PGI, PGM-1, peptidase C, 6PGD, 2,3-DPGAM, NADP-ICD, and acid phosphatase variants, suggesting that these loci are autosomal as in man.
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PMID:Intraspecific red cell enzyme variation in the pigtailed macaque (Macaca nemestrina). 114 87

Red cell adenosine deaminase (ADA-RBC) activity in patients with myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria is significantly increased compared to that observed in normal controls. ADA-RBC activity is not related to fetal hemoglobin concentration, but it is significantly correlated with hemoglobin concentration at diagnosis and with the degree of morphologic dysplasia in the erythroid lineage. The results of our study suggest that the observed enzymatic abnormality may constitute a non-specific manifestation of the stem cell alteration that determines these disorders.
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PMID:Biologic relevance of elevated red cell adenosine deaminase activity in myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria. 129 30

Previous studies have indicated a possible role for polymorphonuclear leukocytes (PMNLs) in the maintenance of hemostasis and vascular tone. We now demonstrate that unstimulated isolated PMNLs maintained at 37 degrees inhibited human platelet aggregation in a concentration- and time-dependent fashion. In addition, PMNLs increased platelet cyclic GMP concentrations. The platelet aggregation inhibitory effect of PMNLs was potentiated by superoxide dismutase and attenuated by hemoglobin and methylene blue. This inhibitory effect of PMNLs was not observed in 48-hr-old killed cells and was not modulated by aspirin treatment or by adenosine deaminase. These observations suggest that human PMNLs maintained at 37 degrees produce a substance with biological characteristics similar to those of the endothelium-derived relaxing factor.
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PMID:Inhibitory effect of unstimulated neutrophils on platelet aggregation by release of a factor similar to endothelium-derived relaxing factor (EDRF). 224 28

Fludarabine (9-beta-D-arabinofuranosyl 2-fluoro-adenine monophosphate) is a fluorinated analogue of adenine which is relatively resistant to deamination by adenosine deaminase. Phase I clinical trials disclosed significant antitumor activity in lymphoid malignancies. Fludarabine has been used in the treatment of CLL since March, 1985, at a dose of 25-30 mg/m2/day x 5 days each 3-4 weeks by short intravenous infusion. Sixty-eight previously treated patients with CLL are evaluable for response. The median age was 60 years, 50 were male the median number of prior chemotherapy regimens was 2, and the median time from initial chemotherapy to fludarabine was 45 months. Forty-three (63%) were Rai stages 3 and 4, 31 (46%) were Binet Stage C. Twenty patients (29%) obtained a complete remission (CR), defined as peripheral lymphocytes less than 4,000/microliters, no clinical evidence of disease, less than 30% of lymphocytes in the bone marrow (with no residual nodules), or a nodular partial remission, NPR (CR except for residual lymphoid nodules), and 19 (28%) a partial remission (less than 50% reduction in tumor in nodes, liver, spleen and bone marrow and greater than 1 log reduction in the lymphocyte count). The complete remission rate for the various involved sites were blood (69%), liver (52%), spleen (55%), and nodes (48%). The bone marrow was the least responsive site with 16% CR and 44% PR. The number of prior regimens did not have a significant response rate or survival. The serum albumin , alkaline phosphatase, platelet and hemoglobin level all were associated with survival from the start of fludarabine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fludarabine therapy in chronic lymphocytic leukemia (CLL). 246 94

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

Erythrocytes contain a high concentration of cytosolic adenosine deaminase and this enzyme activity is present in preparations of stroma-free hemoglobin (SFHS). The documented vasoconstrictor activity of SFHS preparations does not appear to be due to interference with endogenous adenosine-mediated mechanisms, because removal of greater than 80% of adenosine deaminase activity failed to affect the vasoconstrictor potency of SFHS preparations. We have also demonstrated the presence of a contractility-depressant activity in SFHS when the latter was added to aqueous buffer perfusing rat Langendorff-hearts. This activity is diminished in phosphocellulose-purified preparations with reduced adenosine deaminase activity but is not necessarily causally related to this enzyme.
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PMID:Adenosine deaminase in stroma-free hemoglobin solution is not responsible for coronary vasoconstriction. 278 59

The human erythrocyte generates high-energy adenosine triphosphate by anaerobic glycolysis and cycles oxidized and reduced nicotinamide adenine dinucleotide phosphate by the aerobic pentose phosphate shunt pathway. Certain enzymopathies of the pentose phosphate shunt are associated with hemolysis resulting from oxidative denaturation of hemoglobin. Glucose-6-phosphate dehydrogenase deficiency, an X-chromosome-linked disorder, is the prototype of these diseases and is genetically and clinically polymorphic. Six enzymopathies of anaerobic glycolysis cause hemolytic anemia; lactate dehydrogenase deficiency does not. In 2,3-diphosphoglycerate mutase deficiency, 2,3-diphosphoglycerate is greatly reduced and asymptomatic polycythemia is noted. Pyrimidine-5'-nucleotidase deficiency, an enzymopathy of nucleotide metabolism, is characterized by intracellular accumulations of pyrimidine-containing nucleotides, marked basophilic stippling on the stained blood film, splenomegaly, and hemolysis. Lead inhibits the nucleotidase and an identical syndrome occurs during severe lead poisoning. Hemolysis also accompanies an unusual enzymopathy characterized by a 40- to 70-fold increase (not decrease) in adenosine deaminase activity.
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PMID:Hemolytic anemias and erythrocyte enzymopathies. 299 Feb 76

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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