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)

Inherited deficiency of the purine salvage enzyme adenosine deaminase (ADA) gives rise to a syndrome of severe combined immunodeficiency (SCID). We have studied a 2.5-yr-old immunologically normal child who had been found to lack ADA in his erythrocytes during New York State screening of normal newborns. His erythrocytes were not detectably less deficient in ADA than erythrocytes of ADA(-)-SCID patients. In contrast, his lymphocytes and cultured long-term lymphoid cells contained appreciably greater ADA activity than those from patients with ADA(-)-SCID. This residual ADA activity had a normal molecular weight and K(m) but was markedly unstable at 56 degrees C. His residual erythrocytes-ADA activity also appeared to have diminished stability in vivo. ADA activity in lymphoid line cells of a previously reported erythrocyte-ADA-deficient!Kung tribesman was found to contain 50% of normal activity and to exhibit diminished stability at 56 degrees C. ATP content of erythrocytes from both partially ADA-deficient individuals was detectably greater than normal (12.3 and 6.1 vs. normal of 2.6 nmol/ml packed erythrocytes). However, the dATP content was insignificant compared to that found in erythrocytes of ADA(-)-SCID patients (400-1,000 nmol/ml packed erythrocytes). The New York patient, in contrast to normals, excreted detectable amounts of deoxyadenosine, but this was <2% of deoxyadenosine excreted by ADA(-)-SCID patients. Thus, the residual enzyme in cells other than erythrocytes appears to be sufficient to almost totally prevent accumulation of toxic metabolites.
...
PMID:Erythrocyte adenosine deaminase deficiency without immunodeficiency. Evidence for an unstable mutant enzyme. 47 73

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.
...
PMID:A case of red-cell adenosine deaminase overproduction associated with hereditary hemolytic anemia found in Japan. 73 30

Strains of Escherichia coli K-12 containing various combinations of pur (de novo synthesis of purines), pup (purine nucleoside phosphorylase), add (adenosine deaminase) and apt (adenine phosphoribosyl transferase) mutations have been constructed. The apt mutation blocks the ability of strains of pur add and pur add pup genotype to utilize both adenine and adenosine as sole purine sources. Exogenously supplied histidine (that blocks conversion of AMP to guanine nucleotides) does not reduce the growth rate of the strain of pur apt genotype on adenosine as the sole purine source. Adenine released into the cultural medium of bacteria containing simultaneously apt and pup mutations. This data suggest that cultures of E. coli are unable to phosphorylate adenosine to AMP and that they are capable to degrade adenosine to free adenine without participation of purine nucleoside phosphorylase (gene pup).
...
PMID:[Phenotypic manifestation of mutations involving resistance to 2,6-diaminopurine (apt) in the genome of purine auxotrophs of Escherichia coli K-12]. 79 27

T lymphocytes cultured from a patient (T.D.) with adenosine deaminase (ADA) deficiency expressed ADA activity in the normal range, inconsistent with her severe immunodeficiency, metabolic abnormalities, and with the absence of ADA activity in her B lymphocytes and other nucleated hematopoietic cells. ADA from T.D. T cells had normal Km, heat stability, and sensitivity to ADA inhibitors. Examination of HLA phenotype and polymorphic DNA loci indicated that T.D. was neither chimeric nor a genetic mosaic. Amplified and subcloned ADA cDNA from ADA+ T.D. T cells was shown by allele-specific oligonucleotide hybridization to possess the same mutations (Arg101----Trp, Arg211----His) previously found in the ADA-T.D. B cell line GM 2606 (Akeson, A. L., D. A. Wiginton, M. R. Dusing, J. C. States, and J. J. Hutton. 1988. J. Biol. Chem. 263:16291-16296). Our findings suggest that one of these mutant alleles can be expressed selectively in IL-2-dependent T cells as stable, active enzyme. Cultured T cells from other patients with the Arg211----His mutation did not express significant ADA activity, while some B cell lines from a patient with an Arg101----Gln mutation have been found to express normal ADA activity. We speculate that Arg101 may be at a site that determines degradation of ADA by a protease that is under negative control by IL-2 in T cells, and is variably expressed in B cells. Il-2 might increase ADA expression in T cells of patients who possess mutations of Arg101.
...
PMID:Paradoxical expression of adenosine deaminase in T cells cultured from a patient with adenosine deaminase deficiency and combine immunodeficiency. 197 54

The goal of the research reported here is to identify evolutionarily conserved amino acid residues associated with enzymatic deamination of adenosine. To do this, we isolated molecular clones of the Escherichia coli adenosine deaminase gene by functional complementation of adenosine deaminase deficient bacteria and deduced the amino acid sequence of the enzyme from the nucleotide sequence of the gene. Nucleotide sequence analysis revealed the presence of a 996-nucleotide open reading frame encoding a protein of 332 amino acids having a molecular weight of 36,345. The deduced amino acid sequence of the E. coli enzyme has approximately 33% identity with those of the mammalian adenosine deaminases. With conservative amino acid substitutions the overall sequence homology approaches 50%, suggesting that the structures and functions of the mammalian and bacterial enzymes are similar. Additional amino acid sequence analysis revealed specific residues that are conserved among all three adenosine deaminases and four AMP deaminases for which sequence information is currently available. In view of previously published enzymological data and the conserved amino acid residues identified in this study, we propose a model to account for the enzyme-catalyzed hydrolytic deamination of adenosine. Potential catalytic roles are assigned to the conserved His 214, Cys 262, Asp 295, and Asp 296 residues of mammalian adenosine deaminases and the corresponding conserved amino acid residues in bacterial adenosine deaminase and the eukaryotic AMP deaminases.
...
PMID:Deduced amino acid sequence of Escherichia coli adenosine deaminase reveals evolutionarily conserved amino acid residues: implications for catalytic function. 199 86

1. The effects of several drugs, including antagonists of vasoactive intestinal peptide (VIP), and antisera to VIP or peptide histidine isoleucine (PHI), on relaxation responses of guinea-pig isolated trachea to electrical field stimulation (EFS) have been examined. 2. beta-Adrenoceptor blockade with propranolol only partially blocked the inhibitory response to EFS, but had no effect in tissues from animals pretreated with 6-hydroxydopamine or reserpine. 3. Neither adenosine deaminase, in the presence of dipyridamole, nor the potent adenosine antagonist NPC205 (1,3-n-dipropyl-8-(4-hydroxyphenyl)-xanthine) had any effect on the inhibitory response to EFS. 4. The VIP antagonists, [Ac-Tyr1, D-Phe2]-GRF(1-29)-NH2 and [4-Cl-D-Phe6, Leu17]-VIP had no effect on the inhibitory response to EFS. Moreover, they were without effect on responses to exogenous VIP or PHI. 5. Overnight incubation with VIP antisera markedly reduced the inhibitory response to EFS. PHI antisera had a similar, but smaller effect. 6. In the presence of a concentration of VIP that is maximal for its relaxant effect, inhibitory responses to electrical stimulation were greatly inhibited. 7. Naloxone and reactive blue 2 each had no effect on inhibitory responses indicating that endogenous opioids and adenosine 5'-triphosphate (ATP) respectively are not involved. 8. The results suggest that VIP and PHI, but not adenosine, contribute to non-adrenergic, noncholinergic inhibitory nerve responses of guinea-pig trachea. Moreover, the surprising lack of effect of both VIP antagonists on these responses, and in particular, on responses to exogenous VIP, suggests that the receptors mediating VIP-induced tracheal relaxation are different from those that mediate pancreatic secretion.
...
PMID:The effects of vasoactive intestinal peptide (VIP) antagonists, and VIP and peptide histidine isoleucine antisera on non-adrenergic, non-cholinergic relaxations of tracheal smooth muscle. 272 Feb 90

Two main candidates have been proposed for the role of relaxant neurotransmitter in the intestine: (a) the purine nucleotide, 5'-adenosine triphosphate (ATP) and (b) the neuropeptide, vasoactive intestinal peptide (VIP). The candidacy of VIP is favored by its precise location in nerve fibers that innervate circular smooth muscle and tenia coli. We have used a photoaffinity analog of ATP, 3'-O-(4-Benzoyl)benzoyl ATP, that binds irreversibly to ATP receptors and inactivates them in the presence of light, and a specific VIP antiserum to examine the claims of VIP and ATP as relaxant neurotransmitters in tenia coli of the guinea pig. Both VIP and ATP caused dose-dependent, tetrodotoxin-insensitive relaxation of tenia coli. The effect of ATP was equipotent to that of its stable isostere alpha, beta-methylene ATP and resistant to degradation by adenosine deaminase, indicating interaction of ATP with purinergic-P2 receptors. Photoactivated 3'-O-(4-Benzoyl) benzoyl adenosine triphosphate selectively inhibited relaxation induced by ATP but had no effect on relaxation induced by VIP or by field (i.e., neural) stimulation. Vasoactive intestinal peptide antiserum (final dilution 1:60), on the other hand, inhibited relaxation caused by VIP and by field stimulation but had no effect on relaxation caused by ATP. Neither normal rabbit serum nor preneutralized VIP antiserum had any effect on relaxation induced by ATP, VIP, or field stimulation. Inhibition of neurally induced relaxation by VIP antiserum ranged from 52% +/- 7% (p less than 0.01) at the lowest frequency of stimulation to 15% +/- 4% (p less than 0.01) at the highest frequency, consistent with competitive interaction between antiserum and neurally released VIP. Near-maximal field stimulation at 1 Hz caused an eightfold (800% +/- 49%, p less than 0.01) increase in VIP release into the bathing medium. The results favor VIP (and probably peptide histidine isoleucine, a relaxant homologue known to be cosynthesized with VIP) as the main neural mediator of relaxation in tenia coli.
...
PMID:Vasoactive intestinal peptide. Relaxant neurotransmitter in tenia coli of the guinea pig. 286 Nov 38

Adenosine deaminase (ADA; adenosine aminohydrolase, EC 3.5.4.4) deficiency is one cause of the genetic disease severe combined immunodeficiency. To identify mutations responsible for ADA deficiency, we synthesized cDNAs to ADA mRNAs from two cell lines, GM2756 and GM2825A, derived from ADA-deficient immunodeficient patients. Sequence analysis of GM2756 cDNA clones revealed a different point mutation in each allele that causes amino acid changes of alanine to valine and arginine to histidine. One allele of GM2825A also has a point mutation that causes an alanine to valine substitution. The other allele of GM2825A was found to produce an mRNA in which exon 4 had been spliced out but had no other detrimental mutations. S1 nuclease mapping of GM2825A mRNAs showed equal abundance of the full-length ADA mRNA and the ADA mRNA that was missing exon 4. Several of the ADA cDNA clones extended 5' of the major initiation start site, indicating multiple start sites for ADA transcription. The point mutations in GM2756 and GM2825A and the absence of exon 4 in GM2825A appear to be directly responsible for the ADA deficiency. Comparison of a number of normal and mutant ADA cDNA sequences showed a number of changes in the third base of codons. These changes do not affect the amino acid sequence. Analyses of ADA cDNAs from different cell lines detected aberrant RNA species that either included intron 7 or excluded exon 7. Their presence is a result of aberrant splicing of pre-mRNAs and is not related to mutations that cause ADA deficiency.
...
PMID:Mutations in the human adenosine deaminase gene that affect protein structure and RNA splicing. 347 10

Adenosine as well as hypoxia and ischemia are known to cause atrioventricular conduction block. To test the hypothesis that adenosine is the primary mediator of hypoxia-induced atrioventricular conduction delay in isolated perfused guinea pig hearts, we characterized a) the time courses of hypoxia-induced adenosine release and delay in atrioventricular conduction, b) the relationships between oxygen tension, adenosine concentration in the effluent, and atria-to-His-bundle interval, and c) the adenosine receptor mediating the negative dromotropic effect of hypoxia. Oxygen tension and effluent adenosine levels were linearly related with a correlation coefficient (r) of -0.85 and a slope of -6.3 +/- 0.37 pmol/min/g/torr. Likewise, oxygen tension and atria-to-His-bundle interval prolongation were linearly related with r = -0.85 and a slope of -0.180 +/- 0.013 msec/torr. The EC50 of effluent adenosine in causing atria-to-His-bundle prolongation was 0.26 +/- 0.02 microM. Adenosine deaminase, an enzyme that deaminates adenosine to inosine and is limited to the extracellular space, significantly attenuated (61%) the atria-to-His-bundle interval prolongation caused by hypoxia. This prolongation was further reduced (81%) by a combination of adenosine deaminase and theophylline, an adenosine receptor blocker. Adenosine deaminase also reduced (by 95%) the atria-to-His-bundle interval prolongation in normoxic recipient hearts caused by the effluent of hypoxic donor hearts. Several adenosine antagonists, i.e., theophylline, 8-phenyltheophylline, and 8-(p-sulfophenyl)theophylline antagonized in a dose-dependent manner the negative dromotropic effect of exogenous adenosine and hypoxia. Schild analysis of the antagonism of hypoxia-induced atria-to-His-bundle interval prolongation by 8-(p-sulfophenyl)theophylline yielded the following pA2 values: 5.30 +/- 0.25 and 5.28 +/- 0.31 using oxygen tension and effluent adenosine vs. AH interval prolongation, respectively. 8-(p-Sulfophenyl)theophylline also antagonized to an equal extent atria-to-His-bundle interval prolongations of similar magnitude caused either by adenosine or hypoxia. We conclude that 1) adenosine is the primary mediator of hypoxia-induced atrioventricular conduction delay, and 2) the adenosine receptor that mediates the negative dromotropic effect of hypoxia is similar to that of exogenous adenosine.
...
PMID:Effect of adenosine on atrioventricular conduction. II: Modulation of atrioventricular node transmission by adenosine in hypoxic isolated guinea pig hearts. 379 84

Supplementing the salts-glucose medium of Escherichia coli with adenine initiates induction of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4), growth inhibition, and an increased potential for the net deamination of adenine. The extent and duration of these events are proportional to the initial adenine concentration and are dependent upon adenylate pyrophosphorylase and repression of histidine biosynthesis for maximal expression. The conversion of adenine to hypoxanthine, though limited in rate, occurs concurrently with induction and accounts for the progressively decreasing rate of deaminase induction, since hypoxanthine is a relatively ineffective inducer. The subsequent decrease in deaminase activity is due to dilution by continued cell division and by enzyme inactivation which occurs during the late-log and early-stationary phases. The partially purified deaminase is labile to a number of environmental conditions, particularly to phosphate buffers of pH 6.8 or less. A disproportionately slow rate of adenine deamination by cells utilizing lactate permits a more prolonged period of induction and, consequently, a greater quantity of enzyme to be synthesized; cell division, but not enzyme inactivation, reduces enzyme concentration. The adenosine deaminases of Aerobacter aerogenes and Salmonella typhimurium are not inducible.
...
PMID:Induction of adenosine deaminase in Escherichia coli. 487 15


1 2 3 4 5 Next >>

---