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

---

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

The red cell lysates of two children with severe combined immunodeficiency disease (SCID) exhibited a virtually total absence of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) when standard volumes were assayed. Under these conditions the parents exhibited depressed specific activity except for one mother, whose lysate showed a normal value for activity. Upon storage of the lysate at 4 degrees, a significant amount of activity appeared in one of the SCID children, and the activity of the heterozygous carriers was stimulated. With the use of a sensitive spectrophotometric assay based on conversion of inosine to uric acid, it was shown that the specific enzymatic activity in each of the SCID patients increased progressively as the volume of lysate assayed was lowered. With the smallest amount of lysate this specific activity was in the normal range. Similarly, the specific activity of each of the parents' lysates increased to the level of normal (or, in one case, about twice normal) as smaller volumes were assayed. The activity in the SCID patient was inhibitable by 2-fluoroadenosine and N6-methyladenosine, known competitive inhibitors of human red cell adenosine deaminase. The lysate from the SCID patient was also shown to inhibit adenosine deaminase partially purified from a normal individual. The results are interpreted in terms of a genetically programmed production of an adenosine deaminase inhibitor in at least one variant of the severe combined immunodeficiency disease.
...
PMID:A normal level of adenosine deaminase activity in the red cell lysates of carriers and patients with severe combined immunodeficiency disease. 106 Nov 4

A proportion of patients suffering from the autosomal recessive form of severe combined immunodeficiency have an inherited deficiency of adenosine deaminase (EC 3.5.4.4; adenosine aminohydrolase) (erythrocyte isoenzyme). We have, however, found residual adenosine deaminase activity in fibroblasts derived from four such patients. The enzyme responsible for this activity is biochemically homologous with the high-molecular-weight tissue isoenzyme of adenosine deaminase found in normal fibroblasts and tissues other than erythrocytes. The residual adenosine deaminase has an altered electrophoretic mobility, increased heat stability as compared to normals, and can be detected in fibroblasts of obligate heterozygotes. Our previous studies have indicated that the tissue and erythrocyte adenosine deaminase isoenzymes contain a common catalytic unit controlled by the gene affected in severe combined immunodeficiency with absent adenosine deaminase (erythrocyte isoenzyme). This residual adenosine deaminase therefore represents, most likely, a "mutant" enzyme in fibroblasts of patients with severe combined immunodeficiency. The data support the hypothesis that, in these patients, severe combined immunodeficiency is due to a mutation at the adenosine deaminase locus.
...
PMID:Characterization of residual enzyme activity in fibroblasts from patients with adenosine deaminase deficiency and combined immunodeficiency: evidence for a mutant enzyme. 106 Nov 19

Adenosine deaminase (EC 3.5.4.4, ADA) has been assayed in lymphocytes, granulocytes and erythrocytes from 45 patients with haematological malignancies. Activities were uniformly low in lymphocytes from patients with chronic lymphocytic leukaemia. Variable, but abnormal activities were frequently found in multiple myeloma, untreated lymphoma and leukaemic reticuloendotheliosis. High values were observed in lymphocytes from patients with lymphoma during intensive combination chemotherapy. ADA levels in lymphocytes were not correlated with levels in granulocytes or erythrocytes. ADA was elevated in blasts of patients with acute lymphocytic and myelogenous leukaemias but the ranges of activities per cell were so similar that ADA assay is unlikely to be of major help in distinguishing the two diseases.
...
PMID:Adenosine deaminase activity in peripheral blood cells of patients with haematological malignancies. 106 90

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.
...
PMID:Purine metabolism in adenosine deaminase deficiency. 106 99

Adenosine aminohydrolase from human spleen was purified 120 fold. In pH 7.3 phosphate buffer at 37 degrees, this enzyme preparation deaminated adenosine and arabinosyladenine (ara-A) with apparent values for the Michaelis constant of 40 muM and 90 muM respectively. The products of both deamination reactions, i.e., inosine and arabinosylhypoxanthine, were competitive inhibitors with Ki equal to 710 muM and 60 muM, respectively. N6-benzyladenosine and 2'-deoxy-N6-benzyladenosine were competitive inhibitors. The former was better able to inhibit ara-A than adenosine deamination, while the latter was equivalent in inhibiting deamination of these two substrates. Evidence for a naturally occurring adenosine aminohydrolase inhibitor in spleen was presented. It is suggested that benzyladenosine and deoxybenzyladenosine might potentiate ara-A chemotherapy of neoplasms and metastates in the spleen and other hemic cells.
...
PMID:Adenosine aminohydrolase from human spleen: partial purification and some kinetic properties. 107 May 12

1. Erythrocyte adenosine deaminase (EC 3.5.4.4) and purine nucleoside (inosine) phosphorylase (EC 2.4.1.1) were measured in 33 healthy controls and 43 primary gouty subjects. Adenosine deaminase activity in controls and gouty subjects was 0.373 plus or minus 0.108 and 0.457 plus or minus 0.140 A unit per 5-10-3 ml packed red cells per h, respectively. The difference was statistically significant (P less than 0.01). Mean adenosine deaminase: inosine phosphorylase (X10) in primary gout was also significantly higher than in controls (P less than 0.05). Inosine phosphorylase activities in the two groups were not significantly different. 2. When gouty patients were divided into two groups according to weight, normal weight gouty subjects had a higher adenosine deaminase activity and an increased ration of adenosine deaminase to inosine phosphorylase when compared with overweight patients (P less than 0.10). In two control groups divided according to the percentage overweight, such differences were not found. In the case of two gouty groups divided according to the existence of gouty heredity, tophi or renal impairment, adenosine deaminase and inosine phosphorylase activity in the two groups were not significantly different. The possible biochemical role of adenosine deaminase activity in primary gout is discussed.
...
PMID:Erythrocyte adenosine deaminase and purine nucleoside phosphorylase activity in gout. 111 66

Affinity chromatography has been used to purify adenosine deaminase from various sources: calf spleen, calf intestinal mucosa, chicken duodena and human erythrocytes. For this purpose a specific inhibitor, 9-(p-aminobenzyl) adenine, was synthesized and covalently joined to agarose. Adenosine deaminase is selectively retained by such an inhibitor-resin when highly impure solutions are chromatographed through it. After elution from the resin with guanylurea, a competitive inhibitor, the enzyme is homogeneous and can be recovered in yields of 80 percent or more and the same number of multiple forms of the enzyme is present in the purified preparation and in the crude extract.
...
PMID:A general method of purification of adenosine deaminase by affinity chromatography. 112 Jun 33

To evaluate the regulation of adenine nucleotide metabolism in relation to purine enzyme activities in rat liver, human erythrocytes and cultured human skin fibroblasts, rapid and sensitive assays for the purine enzymes, adenosine deaminase (EC 2.5.4.4), adenosine kinase (EC 2.7.1.20), hyposanthine phosphoribosyltransferase (EC 2.4.28), adenine phosphoribosyltransferase (EC 2.4.2.7) and 5'-nucleotidase (EC 3.1.3.5) were standardized for these tissues. Adenosine deaminase was assayed by measuring the formation of product, inosine (plus traces of hypoxanthine), isolated chromatographically with 95% recovery of inosine. The other enzymes were assayed by isolating the labelled product or substrate nucleotides as lanthanum salts. Fibroblast enzymes were assayed using thin-layer chromatographic procedures because the high levels of 5'-nucleotidase present in this tissue interferred with the formation of LaCl3 salts. The lanthanum and the thin-layer chromatographic methods agreed within 10%. Liver cell sap had the highest activities of all purine enzymes except for 5'-nucleotidase and adenosine deaminase which were highest in fibroblasts. Erythrocytes had lowest activities of all except for hypoxanthine phosphoribosyltransferase which was intermediate between the liver and fibroblasts. Erhthrocytes were devoid of 5'-nucleotidase activity. Hepatic adenosine kinase activity was thought to control the rate of loss of adenine nucleotides in the tissue. Erythrocytes had excellent purine salvage capacity, but due to the relatively low activity of adenosine deaminase, deamination might be rate limiting in the formation of guanine nucleotides. Fibroblasts, with high levels of 5'-nucleotidase, have the potential to catabolize adenine nucleotides beyond the control od adenosine kinase. The purine salvage capacity in the three tissues was erythrocyte greater than liver greater than fibroblasts. Based on purine enzyme activities, erythrocytes offer a unique system to study adenine salvage; fibroblasts to study adenine degradation; and liver to study both salvage and degradation.
...
PMID:Adenine nucleotide metabolism in relation to purine enzymes in liver, erythrocytes and cultured fibroblasts. 118 98

Report here is the isolation of adenosine deaminase deficient mutants and genetic mapping. Engineering transposon MudJ (lacZ, Kanr) was used for mutagenesis and six add:: MudJ were obtained among 20,000 Kanr transductants. Adenosine deaminase activity of these mutants were assayed and all are negative. Cotransduction analysis of add::MudJ indicated that add is 70% linked to pmi(31') and 37% linked to zxx1900::Tn10d-tet insertion which is 10% linked to purR(30'). Three points cross showed that add is located between pmi and Tn10d-tet insertion. Therefore the gene order is purR-zxx1900::Tn10d-tet-add-pmi.
...
PMID:[Regulation of purine biosynthesis. I. Isolation of add:: MudJ (lacZ, Kanr) insertions and genetic mapping]. 133 59

Severe combined immunodeficiency (SCID) is a heterogeneous syndrome, due to X-linked and autosomal recessive defects. A significant proportion of the autosomal recessive forms of SCID are due to mutations at the adenosine deaminase (ADA) locus. Nine different mutations at the ADA locus, including 7 missense point mutations, have been reported in children with ADA-SCID. We could detect 5 of the 7 missense mutations associated with ADA-SCID by alterations in restriction fragments utilizing standard restriction digestion of genomic DNA and hybridization of radiolabelled ADA genomic probes to Southern transfers. We additionally developed more rapid nonradioactive methods employing digestion of genomic DNA amplified by PCR that also detected all 5 mutations. Using these methods, we have examined a sample of 45 ADA-SCID chromosomes and report that these 5 missense mutations account for one third of the ADA--chromosomes studied, with 2 mutations being relatively common.
...
PMID:Five missense mutations at the adenosine deaminase locus (ADA) detected by altered restriction fragments and their frequency in ADA--patients with severe combined immunodeficiency (ADA-SCID). 134 49


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---