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 specific competitive radioimmunoassay (RIA) was employed to quantify human adenosine deaminase molecules produced in human-Chinese hamster somatic cell hybrids. Studies on a set of hybrids in which the normal and aberrant expressions of adenosine deaminase (assigned earlier to human chromosome 20) were segregating, have demonstrated that in the patient with ADA-SCID disease reported by Herbschleb-Voogt et al. (1981 a), the deficiency of ADA activity was associated with a comparable deficiency of adenosine deaminase specific immuno-crossreacting material (ADA-CRM).
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PMID:Basic defect in the expression of adenosine deaminase in ADA-SCID disease. II. Deficiency of ADA-CRM detected in heterozygote human-Chinese hamster cell hybrids. 684 Jul 56

The somatic cell hybrid method has been used to study the number and different types of human genes involved in the expression of adenosine deaminase (ADA; adenosine aminohydrolase, EC 3.5.4.4) in normal cells and cells from a patient with ADA-deficient severe combined immunodeficiency disease (SCID). Genetic and biochemical characterization of ADA in SCID and the ADA tissue-specific isozymes in normal human cells indicates that additional genes, besides the ADA structural gene on chromosome 20, are involved in ADA expression. Human chromosome 6 encodes a gene, ADCP-1, whose presence is necessary for the expression of an ADA-complexing protein in human-mouse somatic cell hybrids [Koch, G. & Shows, T. B. (1978) Proc. Natl. Acad. Sci. USA 75, 3876-3880]. We report the identification of a second gene, ADCP-2, on human chromosome 2, that is also involved in the expression of the ADA-complexing protein. The data indicate that these two ADCP genes must be present in the same cell for that cell to express the complexing protein. Human-mouse somatic cell hybrids, in which the human parental cells were fibroblastss from an individual with ADA-deficient SCID, also required human chromosomes 2 and 6 to express the ADA-complexing protein, indicating that neither ADCP-1 nor ADCP-2 is involved in the ADA deficiency in SCID. The SCID-mouse hybrid cells expressed no human ADA even when human chromosome 20 had been retained. The deficiency of human ADA in these hybrids maps to human chromosome 20, and therefore is not due to the repression or inhibiton of ADA or its product by unlinked genes or gene products. We propose that the expression of the polymeric ADA tissue isozymes in human cells requires at least three genes: ADA on chromosome 20, ADCP-1 on chromosome 6, and ADCP-2 on chromosome 2. A genetic scheme is presented and the different genes involved in ADA expression and their possible functions are discussed.
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PMID:Somatic cell genetics of adenosine deaminase expression and severe combined immunodeficiency disease in humans. 693 68

A large collection of cultured human tumor cell lines was characterized for the phenotypes of 16 polymorphic enzyme loci: ACP1, ADA, AK1, ESD, FUCA, GLO1, GOT2, G6PD, ME2, PEPA, PEPB, PEPC, PEPD, PGD, PGM1, and PGM3 primarily to detect and monitor against cell line contamination. Among 100 highly characterized cell lines, 59 lines from different patients and 6 pairs of lines (each pair from the same patient's tumor) had unique phenotype combinations and were therefore presumed to be authentic, uncontaminated cell lines. Besides these 71 lines, the remaining 29 lines consisted of several small groups of two to three lines, each group having a different combination and being among the more frequent in the normal population. The 29 lines, therefore, were not suspected to be contaminants. Among unusual findings were the ME2 1 plus 2 phenotype determined for two bladder tumor lines, a G6PD A phenotype found in a line of Caucasian origin determined not to be a HeLa contaminant, and asymmetrical heterozygous phenotypes in several lines. Except for kidney tumor lines, there was no correlation of adenosine deaminase tissue isoenzymes between tumor lines and normal tissues of origin. For several enzymes significant deviations were found in proportions of the phenotypes observed in Caucasian cell lines from expected proportions on the basis of normal population data, indicating possible natural selection among these lines in tissue culture or among the patients of origin.
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PMID:Distinction of seventy-one cultured human tumor cell lines by polymorphic enzyme analysis. 693 74

We have determined concentrations of adenosine, deoxyadenosine, and deoxyATP (dATP) in cord blood from an infant prenatally diagnosed as ADA deficient. Plasma deoxyadenosine and adenosine were already elevated in cord blood (0.7 and 0.5 microM vs. normal of less than 0.07 microM). Elevation of plasma deoxyadenosine has not previously been documented in these children. Erythrocyte dATP content was also elevated at birth (215 nmol/ml packed erythrocytes vs. normal of 2.9). These elevated concentrations of adenosine, deoxyadenosine, and dATP are similar to those we observed in another older adenosine deaminase-deficient patient and may explain the impaired immune function and lymphopenia seen at birth.
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PMID:Plasma deoxyadenosine, adenosine, and erythrocyte deoxyATP are elevated at birth in an adenosine deaminase-deficient child. 696 96

The purpose of this paper was to study the heterogeneity of human thymocytes and leukemic cells of the T-cell line MOLT-3 by velocity sedimentation. Analysis of the subpopulations of thymocytes demonstrated that they represent a heterogeneous population of cells with respect to their size, proliferative activity, and presence and quantities of terminal deoxynucleotidyl transferase and human thymus leukemia-associated antigen, a thymic isozyme of adenosine deaminase (HThy-L/ADA). Only a minor subpopulation of thymocytes (large cells) was in active cycle. The highest level of HThy-L/ADA was associated with the main subpopulation of thymocytes sedimenting at 3 to 4 mm/hr while low amounts of the HThy-L/ADA antigen (enzyme) were found in the minor fractions of the small and large cells. The distribution of terminal deoxynucleotidyl transferase-positive cells indicated that most, but not all, thymocytes contain the enzyme. Analysis of the T-cell line MOLT-3 showed that these cells could be separated into subpopulations with different biochemical and biological properties. More than one subpopulation of cells was capable of DNA synthesis. In contrast to the thymocytes, all fractions of MOLT-3 cells contained high amounts of HThy-L/ADA. The proportion of terminal deoxynucleotidyl transferase-positive cells as a function of sedimentation velocity was also quite constant although there was a slight but reproducible drop in the percentage of these cells in the slowly sedimenting fractions. The percentage of cells with receptors for sheep erythrocytes also remained high in fractions separated on the basis of size, although a consistently higher percentage was found in smaller cells. These studies indicated that thymus cells as well as the malignant T-cell line MOLT-3 can be separated on the basis of sedimentation velocity into subpopulations with different biological and biochemical properties. The data also indicated that the heterogeneity of MOLT-3 line cannot be explained solely on the basis of volume changes due to cell cycle, suggesting that they may represent heterogeneous populations of cells.
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PMID:Heterogeneity of human thymocytes and a malignant T-lymphoblast cell line, MOLT-3. 697 Nov 48

Analysis of human-rodent hybrids showed the following: the assignment of the ADA1 structural gene to chromosome 20; the identification in hybrids of a new ADA, referred to as ADAx, with a migration more rapidly anodal than ADAd and less rapidly anodal than ADA1 (product of allele 1 or 2); ADAx and d are formed by ADA1 and ADCP (an adenosine deaminase complexing protein). ADCP synthesis is controlled, at least, by a gene (ADCP2) localized on chromosome 2, probably in the IDH1 region; the combined action of another gene (ADCP1), assigned by other authors to chromosome 6, could be neither proved nor disproved, if this gene exists, it must be on 6p or in the 6qter region; the presence of chromosomes 20, 2, and 6 does not constitute a sufficient condition for the formation of ADAx and d, in either the hybrids or the human strains or lines: other factors intervene in its formation, i.e., an interaction between the culture medium, the human parental strain or line, and the rodent parental line.
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PMID:[Genetic and epigenetic control of adenosine deaminase expression. Analysis of human and man-mouse hybrid cells (author's transl)]. 697 23

dATP, dADP, and dAMP equalled or exceeded the depleted levels of ATP, ADP, and AMP in erythrocytes from two children with adenosine deaminase (ADA; EC 3.5.4.4) deficiency. dATP and dADP were identified in the mononuclear cells of only one child. The levels of deoxyadenosine compounds fell dramatically after enzyme replacement therapy and were no longer detectable in the urine or in mononuclear cells. Erythrocyte adenosine nucleotide levels showed a corresponding increase. Intact erythrocytes prior to treatment contained adenine, presumed to be from deoxyadenosine degraded during extraction. Adenosine at high concentrations in vitro increased both dATP and ATP levels and decreased intracellular deoxyadenosine levels. There was no significant deamination of either [8-14C]adenosine or deoxyadenosine by intact ADA-deficient erythrocytes. About 90% of adenosine was metabolized to ATP at substrate concentrations from 10-100 microM, compared to 40-60% of deoxyadenosine metabolized to dATP. These studies suggest that (i) high intracellular deoxyadenosine levels may be necessary in vivo to sustain the raised dATP levels in ADA deficiency. (ii) When ADA is inhibited or absent, deoxyadenosine is removed rapidly from the circulation by the human erythrocyte utilizing an adenosine transport system linked to both ADA and adenosine kinase (EC 2.7.1.20).
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PMID:Formation and degradation of deoxyadenosine nucleotides in inherited adenosine deaminase deficiency. 698 23

A deficiency of the enzyme adenosine deaminase is associated with an autosomal recessive form of severe combined immunodeficiency disease in man. The molecular forms of the normal human enzyme have now been well characterized in an effort to better understand the nature of the enzyme defect in affected patients. In some human tissues adenosine deaminase exists predominantly as a small molecular form while in other tissues a large form composed of adenosine deaminase (small form) and an adenosine deaminase-binding protein predominates. The small form of the enzyme purified to homogeneity by antibody affinity chromatography is a monomer of native molecular weight of 37,600. The adenosine deaminase-binding protein, purified by adenosine deaminase affinity chromatography, appears to be a dimer of native molecular weight 213,000 and contains carbohydrate. Based on direct binding measurements, chemical cross-linking studies and sedimentation equilibrium analyses, small form adenosine deaminase has been shown to combine with purified binding protein in a molar ratio of 2:1 respectively to produce the large form adenosine deaminase. Reduced, but widely ranging levels of adenosine deaminating activity, have been reported in various tissues of adenosine deaminase deficient patients. Further, the characteristics of this residual enzyme activity have been analyzed immunochemically to substantiate genetic heterogeneity in this disorder. While many types of immunodeficiency are currently recognized in man, in most cases the molecular defect is unknown. The discovery of a deficiency of the enzyme, adenosine deaminase, ADA, (EC 3.5.4.4), in some patients with severe combined immunodeficiency disease represented an early clue to the pathogenesis of immune dysfunction at the molecular level 1-4. Affected patients with markedly reduced levels of ADA exhibit a defect of both cellular and humoral immunity characterized clinically by severe recurrent infections with a fatal outcome if untreated. Attempts to elucidate the nature of the genetic mutation(s) leading to the reduction of ADA activity in these immunodeficient patients have been complicated in part by an incomplete understanding of the nature of ADA in normal tissues. In this review we will consider the structural characteristics of the normal and mutant forms of ADA as they are currently understood.
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PMID:Analysis of normal and mutant forms of human adenosine deaminase - a review. 698 97

1. In washed guinea-pig brain slices, adenosine uptake inhibitors potentiated the responsiveness of cAMP to adenosine, while an adenosine deaminase inhibitor, 2'-deoxycoformycin, was without effect. 2. In the isolated guinea-pig ileum, uptake was important in terminating the inhibitory action of adenosine on nerve-mediated contractions whereas the ADA inhibitor did not affect the ileum or its responses to adenosine in any way. 3. Adenosine given to mice (100 mg/kg i.p.) or guinea-pigs (250 mg/kg i.p.) caused a small, transient fall in body temperature, accompanied by skeletal-muscle relaxation. 4. In mice this temperature fall was potentiated by the uptake blocker dilazep, although only marginally so by the uptake blocker dipyridamole. The ADA-inhibitor also potentiated the pharmacological responses to adenosine. 5. Responses to adenosine in the guinea-pig were less affected by treatment with uptake or ADA-inhibitors, except when given in combination.
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PMID:Potentiation of pharmacological responses to adenosine, in vitro and in vivo. 706 Sep 20

Adenosine deaminase (adenosine aminohydrolase, EC3.5.4.4) has been purified from human erythrocytes using a simple chromatographic procedure. Purified enzyme was obtained from individuals who were homozygous for the principal isozyme (ADA 1) as well as from individuals who were heterogyzous for the major variant (ADA 2-1). Although ADA 1 and ADA 2-1 are electrophoretically distinguishable, they have many common physical and catalytic properties. No significant differences between the two isozymic forms were found in measurements of molecular weight, catalytic activity in the presence of various substrates and inhibitors, pH optimum, turnover number, and stability in conditions of both high and low pH. ADA 2-1 was, however, substantially less stable than ADA 1 with respect to thermal denaturation. These studies support the idea that adenosine deaminase activity in erythrocytes is lower in those individuals who possess the variant form of the enzyme.
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PMID:Physical and catalytic properties of the isozymes of adenosine deaminase from human red blood cells. 714 44


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