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)

The use of L-glutamate dehydrogenase (GLUD) as a reagent in staining mixtures to detect the isozymes of enzymes which catalyze the production of ammonia has been investigated. Methods have been devised for the electrophoresis and detection, using GLUD, of seven enzymes: cytidine deaminase, adenosine deaminase, adenosine monophosphate deaminase, arginase, argininosuccinase, D-amino acid oxidase, and D-aspartate oxidase. GLUD-linked staining methods appear to be sensitive, specific, and of general application.
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PMID:Detection after electrophoresis of enzymes involved in ammonia metabolism using L-glutamate dehydrogenase as a linking enzyme. 2 58

The effect of adenosine was tested on the energetic metabolism of fed rat liver cells after isolation. The cells were incubated in a buffered saline medium with glucose (5 mM) and adenosine (1 mM) for 30 minutes at 37 degrees C. This increased the concentration of the adenylic nucleotides ATP (+57 per cent, ADP (+39 per cent). Cyclic AMP was increased (+50 per cent) and the intracellular inorganic phosphate decreased (-22 per cent). These changes were accompaned by a decrease of glycogenolysis, glucose consumption and lactate production. Measurement of glycolytic intermediates showed decreased concentrations of fructose 1,6-bis-phosphate and 3-phosphoglycerate proportional to the increase in ATP concentration. The near-equilibrium of the glyceraldehyde 3-phosphate dehydrogenase-phosphoglycerate kinase system was not modified by adenosine. The decrease of the NAD+/NADH ratio along with the increase of the ATP/ADP X PO4 ratio explains the decrease of 3-phosphoglycerate. The decrease in glucose consumption can be explained by the cross over at the phosphofructokinase stage with the decrease of fructose 1,6-bisphosphate. The major part of adenosine was deaminated as indicated by an increase in the production of ammonia and urea. The effects of inosine, or adenosine along with an inhibitor of adenosine deaminase (pentostatin) suggest that adenosine acts on the glucose consumption through adenylic nucleotides. However the increase of the adenylic nucleotide level cannot totally explain the other metabolic changes: decrease of the NAD+/NADH cytoplasmic ratio, constancy of this ratio in mitochondria, decrease of gluconeogenesis from lactate. A direct action of adenosine can therefore be expected.
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PMID:The influence of adenosine on intermediary metabolism of isolated hepatocytes. 23 80

Concanavalin A inhibits serum 5'-nucleotidase activity, without causing significant inhibition of alkaline phosphatase activity. This observation serves as the basis for a new method for assaying the 5'-nucleotidase activity in serum, which depends upon the difference between the enzymic hydrolysis of adenosine-5'-monophosphate in the presence and absence of concanavalin A. A denosine released by the 5'-nucleotidase reaction is deaminated by a coupled reaction with adenosine deaminase to liberate inosine and ammonia, and ammonia is measured colorimetrically by the Berthelot reaction. In sera from 40 healthy adult persons, 5'-nucleotidase activity averaged 6.4 U/liter (SD, +/-2.0; range, 3-12). In sera from 100 patients, measurements of 5'-nucleotidase activity by the new assay averaged 8% lower than by a generally accepted method in which phenyl phosphate is used to suppress hydrolysis of adenosine-5'-monophosphate by alkaline phosphatase activity. The clinical validy of the new assay was tested by measuring serum 5'-nucleotidase activities in rats with bile duct ligation and in rats treated with thioacetamide to induce hepatocellular injury.
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PMID:Inhibition by concanavalin A as the basis for a specific assay of serum 5'-nucleotidase activity. 92 81

Deficiency of erythrocytic and lymphocytic adenosine deaminase (ADA) occurs in some patients with severe combined immunodeficiency disease (SCID). SCID with ADA deficiency is inherited as an autosomal recessive trait. ADA is markedly reduced or undetectable in affected patients (homozygotes), and approximately one-half normal levels are found in individuals heterozygous for ADA deficiency. The metabolism of purine nucleosides was studied in erythrocytes from normal individuals, four ADA-deficiency patients, and two heterozygous individuals. ADA deficiency in intake erythrocytes was confirmed by a very sensitive ammonia-liberation technique. Erythrocytic ADA activity in three heterozygous individuals (0.07,0.08, and 0.14 mumolar units/ml of packed cells) was between that of the four normal controls (0.20-0.37 mumol/ml) and the ADA-deficient patients (no activity). In vitro, adenosine was incorporated principally into IMP in the heterozygous and normal individuals but into the adenosine nucleotides in the ADa-deficient patients. Coformycin (3-beta-D-ribofuranosyl-6,7,8-trihydroimidazo[4,5-4] [1,3] diazepin-8 (R)-ol), a potent inhibitor of ADA, made possible incorporation of adenosine nucleotides in the ADA-deficient patients...
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PMID:Purine nucleoside metabolism in the erythrocytes of patients with adenosine deaminase deficiency and severe combined immunodeficiency. 94 48

Nebularine undergoes hydration at the active site of adenosine deaminase, in a reaction analogous to a partial reaction in the displacement of ammonia from adenosine by water, to generate an inhibitory complex that captures much of the binding affinity expected of an ideal transition-state analogue. Enzyme affinities of several compounds related to nebularine 1,6-hydrate, and to its stable analog 2'-deoxycoformycin, were compared in an effort to identify the structural origins of strong binding. Binding of the stable transition-state analog inhibitor 2'-deoxycoformycin was rendered 9.8 kcal/mol less favorable by removal of substituent ribose, 9.7 kcal/mol less favorable by inversion of the 8-hydroxyl substituent of the diazepine ring, and 10.0 kcal/mol less favorable by removal of atoms 4-6 of the diazepine ring. Binding of the unstable transition-state analog nebularine hydrate was rendered at least 9.9 kcal/mol less favorable by removal of the 6-hydroxyl group and 10.2 kcal/mol less favorable by removal of atoms 1-3 of the pyrimidine ring. In each case, the enzyme exhibited only modest affinity (Kd greater than or equal to 10(-2) M) for the "missing piece", indicating that incorporation of 2 binding determinants within a single molecule permits an additional 7-12 kcal/mol of intrinsic binding energy to be manifested as observed binding energy. These results are consistent with earlier indications that adenosine deaminase may use 10.5 kcal/mol of the intrinsic free energy of binding of the two substrates to place them in positions appropriate for reaction at the active site, overcoming the unfavorable entropy change of -35 eu for the equilibrium of 1,6-hydration of purine ribonucleoside and reducing the equilibrium constant for attainment of the transition state in deamination of adenosine. Thus, adenosine deaminase may achieve up to 8 orders of magnitude of its catalytic power by converting the nonenzymatic, bimolecular, hydration reaction to a monomolecular reaction at its active site. Several new 6-substituted 1,6-dihydropurine ribonucleosides, prepared by photoaddition of formate and by low-temperature addition of organolithium reagents to a derivative of purine ribonucleoside, exhibited Ki values of 9-1400 microM against adenosine deaminase, in accord with the active site's considerable tolerance of bulky leaving groups in substrates. Inhibition by one diastereomer of 6-carboxy-1,6-dihydropurine ribonucleoside was found to be time-dependent, progressing from a weakly bound to a more strongly bound complex.
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PMID:A transition state in pieces: major contributions of entropic effects to ligand binding by adenosine deaminase. 151 Sep 25

Adenosine deaminase is an enzyme that actively participates in the metabolism of the adenine nucleotides. It catalyzes the irreversible hydrolytic deamination of deoxyadenosine and adenosine with the production of deoxyinosine and inosine respectively and of ammonia. This enzyme thus plays an important role in lympho-monocyte maturation and activation. The increase in its activity in different biological fluids (pleural, pericardial, peritoneal, intra-articular and cerebrospinal fluids) has been used as a rapid diagnostic test in tuberculosis infection. In human immunodeficiency virus infection, it was verified that enzymatic activity progressively increases in serum and blood cells, accompanying the natural evolution of the disease. The physiopathological mechanism has not been definitely established but the CD4+ lymphocytes and macrophages are pointed to as being accountable for the enzyme's increase in activity. For this reason, adenosine deaminase could be a marker of the cellular immune response. The study of adenosine deaminase activity in blood cells elucidated the diagnosis of severe combined immunodeficiency (due to a congenital lack of the enzyme) in 30 to 50% of the cases. One type of congenital hemolytic anemia is due to an exaggerated enzymatic activity in red blood cells.
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PMID:[Adenosine deaminase. A pluridisciplinary enzyme]. 180 98

We have measured cyclic GMP accumulation in co-cultures of bovine aortic endothelial cells and rat smooth muscle cells as an index of endothelium-derived relaxing factor (EDRF) production. Adenosine deaminase (EC 3.5.4.4, Sigma type VI) produced a 5- to 10-fold increase in the basal and bradykinin-stimulated cyclic GMP content of co-cultures but had no effect on smooth muscle cells alone. Cyclic GMP accumulation in response to adenosine deaminase was not blocked by adenosine deaminase inhibitors or affected by adenosine, the products of adenosine deamination (inosine and ammonia), or adenosine receptor antagonists. Since superoxide anion is known to destroy EDRF and nitric oxide (NO) (which is similar or identical to EDRF in composition), we tested for superoxide dismutase (SOD, EC 1.15.1.1) in single lots of eight commercial sources of adenosine deaminase by measuring inhibition of the superoxide-mediated reduction of cytochrome c. SOD activity was found in all sources of adenosine deaminase, but varied widely. One lot of Sigma type VI enzyme contained 0.08 units SOD/unit adenosine deaminase. The EC50 values of purified SOD (0.23 units/mL) and Sigma type VI adenosine deaminase (2.1 units/mL) needed to increase the cyclic GMP content of co-cultures differed by a similar factor, 0.11. Thus, the SOD activity in adenosine deaminase is sufficient to account for its effect on cyclic GMP accumulation. One lot of Boehringer Mannheim adenosine deaminase contained much less SOD contamination (0.006 units SOD/unit adenosine deaminase) and produced much less accumulation of cyclic GMP in co-cultures. Cyclic GMP accumulations in response to adenosine deaminase and SOD were both abolished by the NO synthetase inhibitor NG-monomethyl-L-arginine (0.1 mM), consistent with the idea that these enzymes act by stabilizing EDRF. Adenosine deaminase and the SOD activity contaminating it were found to have similar molecular masses of 33-34 kD as assessed by gel permeation chromatography. When run under reducing conditions to dissociate homodimeric SOD into monomers, a 16.6 kD peptide which co-migrates with purified cupro-zinc SOD was visible in silver-stained sodium dodecyl sulfate-polyacrylamide gels of the Sigma type VI but not the Boehringer Mannheim adenosine deaminase. We conclude that commercial sources of adenosine deaminase are variably contaminated by SOD. Since EDRF is synthesized by many tissues, the use of adenosine deaminase contaminated with SOD may produce numerous effects not attributable to the deamination of adenosine.
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PMID:Contamination of adenosine deaminase by superoxide dismutase. Stabilization of endothelium-derived relaxing factor. 184 47

The present study deals with the effect of atrazine on nitrogen metabolism in the liver and brain of fish. Significant changes were seen in the levels of proteins, free amino acids, ammonia, urea, glutamine and the activity levels of proteases, glucogenic aminotransferases, branched-chain aminotransferases, glutamate dehydrogenase, glutaminase, arginase, AMP deaminase and adenosine deaminase in both the tissues of fish exposed to sublethal concentration of atrazine. The study reflects a shift in nitrogen concentration of atrazine. The study reflects a shift in nitrogen metabolism in the tissues of fish for efficient mobilization of end products of protein catabolism as a consequence of atrazine.
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PMID:Modulations in nitrogen metabolism in the hepatic and neuronal tissues of fish, Tilapia mossambica exposed to atrazine. 185 31

At sublethal concentrations, cypermethrin caused a decrease in total proteins and an increase in free amino acids, protease, alanine aminotransferase and aspartate aminotransferase in liver, brain and gill tissues of Tilapia mossambica. Nitrogen metabolic profiles like ammonia, urea and glutamine were also elevated in all the tissues as a consequence of cypermethrin toxicity. Glutamate dehydrogenase, AMP deaminase and adenosine deaminase activity was also increased in the present study.
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PMID:Cypermethrin induced changes in nitrogen metabolism of fish, Tilapia mossambica. 187 79

Twenty-five beagles weighing 9.1 +/- 0.4 kg were used to investigate the arrhythmogenic effects of divided doses of intracoronary norepinephrine (50-200 ng.kg-1.min-1) in the absence and the presence of adenosine deaminase (5 U.kg-1.min-1). A dose of norepinephrine (100 ng.kg-1.min-1) that caused 66 +/- 17% ectopy in the absence of adenosine deaminase caused only 16 +/- 14% ectopy (P less than 0.05) in the presence of the enzyme. Ventricular tachycardia caused by 200 ng.kg-1.min-1 norepinephrine was reduced from 1.2 +/- 0.3 to 0.1 +/- 0.1 bouts/10 cardiac cycles (P less than 0.05) by adenosine deaminase. In five additional dogs, intracoronary adenosine (0.11 mumol/min) terminated sustained norepinephrine-induced (200 ng.kg-1.min-1) ventricular tachycardia within 23 +/- 9 s (P less than 0.05). As long as the adenosine infusion was maintained, a normal sinus rhythm was observed. We conclude that both adenosine and adenosine deaminase significantly attenuate norepinephrine-induced ventricular arrhythmias. A common element beyond the deamination of adenosine, quite possibly ammonia, appears to account for these results.
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PMID:Adenosine deaminase and adenosine attenuate ventricular arrhythmias caused by norepinephrine. 200 Sep 91


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