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)

14C-adenosine is incorporated very little inot nucleic acids of Drosophila cells cultured in a medium free of foetal calf serum. The greater part of the radioactivity is recovered in inosine and hypoxanthine. These results suggest that the principal pathway of ultilization of adenosine is not mediated by adenosine kinase. Adenosine is rapidly deaminated to inosine by adenosine deaminase, and cleaved to hypoxanthine by inosine phosphorylase. Inosine and hypoxanthine not being substrates for Drosophila cell lines, are released into the culture medium.
...
PMID:[Purine metabolism in cultured Drosophila melanogaster cells: adenosine utilization]. 81 92

The finite life-span of fibroblasts in culture may reflect aging at the cellular level and gout is clinical condition whose incidence also increases with age. In order to better understand the age-related changes in purine metabolism, activities of purine degrading (adenosine deaminase and 5'-nucleotidase) and reutilizing (adenine phosphoribosyltransferase, hypoxanthine phosphoribosyl-transferase and adenosine kinase) enzymes were measured in serially cultured skin fibroblasts from normal subjects and from gouty patients who overproduce uric acid. Serially cultured fibroblasts from gouty overproducers of uric acid displayed increased purine enzyme levels with increasing cell passage while fibroblasts from normal donors showed little change in activity. There was no alteration in relative degrading and reutilizing enzyme levels. The data suggest an increase in the rate of purine turnover in aging gouty fibroblasts compared with normal fibroblasts.
...
PMID:Activities of purine pathway enzymes in gouty human fibroblasts aged in vitro. 83 27

Hereditary hemolytic anemia, a dominantly transmitted disorder, has affected 12 family members spanning three generations. The concentration of adenosine triphosphate in the red cells was about half that of comparably reticulocyte-rich blood. Since adenosine deaminase and adenosine kinase compete for a common substrate, the greatly increased activity of the former may interfere with nucleotide salvage via the latter.
...
PMID:Hereditary hemolytic anemia with increased red cell adenosine deaminase (45- to 70-fold) and decreased adenosine triphosphate. 83 88

The association of a human genetic deficiency of adenosine deaminase activity with combined immunodeficiency prompted a study of the effects of adenosine and of inhibition of adenosine deaminase activity on human lymphocyte transformation and a detailed study of adenosine metabolism throughout phytohemagglutinin-induced blastogenesis. The adenosine deaminase inhibitor, coformycin, at a concentration that inhibited adenosine deaminase activity more than 95%, or 50 muM adenosine, did not prevent blastogenesis by criteria of morphology or thymidine incorporation into acid-precipitable material. The combination of coformycin and adenosine, however, substantially reduced both the viable cell count and the incorporation of thymidine into DNA in phytohemagglutinin-stimulated lymphocytes. Incubation of lymphocytes with phytohemagglutinin for 72 h produced a 12-fold increase in the rate of deamination and a 6-fold increase in phosphorylation of adenosine by intact lymphocytes. There was no change in the apparent affinity for adenosine with either deamination or phosphorylation. The increased rates of metabolism, apparent as early as 3 h after addition of mitogen, may be due to increased entry of the nucleoside into stimulated lymphocytes. Increased adenosine metabolism was not due to changes in total enzyme activity; after 72 h in culture, the ratios of specific activities in extracts of stimulated to unstimulated lymphocytes were essentially unchanged for adenosine kinase, 0.92, and decreased for adenosine deaminase, 0.44. As much as 38% of the initial lymphocyte adenosine deaminase activity accumulated extracellularly after a 72-h culture with phytohemagglutinin. In phytohemagglutinin-stimulated lymphocytes, the principal route of adenosine metabolism was phosphorylation at less than 5 muM adenosine, and deamination at concentrations greater than 5 muM. In unstimulated lymphocytes, deamination was the principal route of adenosine metabolism over the range of adenosine concentrations studied (0.5-250 muM). These studies demonstrate the dependence of both the unstimulated and stimulated lymphocyte on adenosine and may account for the observed sensitivity of mitogen-stimulated lymphocytes to the toxic effects of exogenously supplied adenosine in the presence of the adenosine deaminase inhibitor coformycin. A single case of immunodeficiency disease has been reported in association with purine nucleoside phosphorylase deficiency. The catabolism of guanosine was also found to be enhanced in stimulated normal lymphocytes; phosphorolysis of guanosine to guanine by intact lymphocytes increased six fold after 72-h culture with phytohemagglutinin. The specific activity of purine nucleoside phosphorylase in extracts, with guanosine as substrate, was essentially the same in stimulated and unstimulated lymphocytes after 72 h of culture.
...
PMID:Adenosine metabolism in phytohemagglutinin-stimulated human lymphocytes. 95 93

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

Relative involvement of adenosine deaminase and adenosine kinase in antinociception induced by endogenous adenosine was investigated. Antinociception induced by 5'-amino 5'-deoxyadenosine (5'-ADAdo; an adenosine kinase inhibitor) and deoxycoformycin (dCF; an adenosine deaminase inhibitor) administered i.t. was determined using the mouse tail-flick assay. Dose- and time-dependent antinociception was observed following i.t. administration of 5'-ADAdo, but not dCF. Antinociception induced by 5'-ADAdo was reversed by coadministration i.t. of theophylline, an adenosine receptor antagonist, in a dose-dependent manner. These data provide preliminary evidence that adenosine kinase plays a more significant physiological role than adenosine deaminase in the regulation of adenosine involved in spinally-mediated antinociception.
...
PMID:Spinally-mediated antinociception is induced in mice by an adenosine kinase-, but not by an adenosine deaminase-, inhibitor. 143 56

Regulation of blood flow and mitochondrial respiration in the heart would be clarified by improved knowledge of interstitial concentrations and cellular production rates of adenosine; however, these variables cannot be measured directly. To interpret indexes that are available, a comprehensive mathematical model was developed, based on a large body of experimental data. The model describes most of the important pathways of capillary-tissue transport and cellular metabolism of adenosine in the guinea pig heart. It includes capillary flow, solute transport between tissue regions, nonlinear enzyme kinetics for adenosine kinase and adenosine deaminase, and reversible biunireactant kinetics for S-adenosylhomocysteine hydrolase in cardiomyocytes and endothelial cells, intracellular production of adenosine via AMP hydrolysis and transmethylation, and extracellular production of adenosine. A single set of parameter values for the model was obtained in the first stage of the analysis by taking certain values directly from published sources, other values were subject to specific constraints, and other values were determined by parameter optimization. The effects of flow and endothelial metabolism on the relation between interstitial and venous adenosine concentrations were determined. The relation between myocardial adenosine production rate and S-adenosylhomocysteine accumulation in the presence of excess homocysteine was estimated. In the second stage of the analysis, the model was used to investigate the mechanism of myocardial adenosine production, without changing the parameter values. Cellular adenosine production rates were estimated by fitting measurements of venous adenosine release obtained during altered energetic conditions in experiments by different investigators. The original results showed a dissociation between measurements of cytosolic AMP concentrations and venous adenosine release. It is concluded that 1) it is essential to account for the effect of flow on interstitial and venous adenosine concentrations, since decreased flow may produce effects outwardly resembling inhibition of the enzyme 5'-nucleotidase, 2) adenosine concentrations in epicardial transudate are not in equilibrium with interstitial fluid, and 3) the rate of cellular adenosine production increases monotonically with free cytosolic concentrations of AMP during a variety of alterations in energy balance of the guinea pig heart.
...
PMID:Comprehensive model of transport and metabolism of adenosine and S-adenosylhomocysteine in the guinea pig heart. 149 7

The relationship between transport and metabolism in synaptoneurosomes was examined to determine the metabolic stability of rapidly accumulated D-[3H]adenosine and L-[3H]adenosine and the degree to which metabolism of the accumulated purines affected measurements of apparent KT and Vmax values for adenosine transport. For D-[3H]adenosine, high- and low-affinity accumulation processes were present. For the high-affinity system an inverse relationship was found between transport reaction times and KT and Vmax values. For incubations of 5, 15, and 600 s, which corresponded to 24, 32, and 76% phosphorylation of accumulated D-[3H]adenosine to nucleotides, apparent KT values were 9.4, 8.4, and 4.5 microM, respectively, and Vmax values were 850, 70, and 12 pmol/min/mg of protein, respectively. Pretreatment with 10 microM erythro-9-(2-hydroxy-3-nonyl)adenine, an adenosine deaminase inhibitor, and 5'-iodotubercidin, an adenosine kinase inhibitor, decreased the phosphorylation of accumulated D-[3H]adenosine to 6% with 5-s and 9% with 15-s incubations. This resulted in significantly higher KT values: 36 microM at 5 s and 44 microM at 15 s. At 10-min incubations in the presence of these inhibitors, metabolism of accumulated D-[3H]adenosine was 32%, and apparent KT and Vmax values at this time were not significantly different from those obtained without inhibitors. For L-[3H]adenosine, apparent KT and Vmax values for 20-s incubations were 38.7 microM and 330 pmol/min/mg of protein, respectively. Metabolism (mainly phosphorylation) of accumulated L-[3H]adenosine was observed only at incubations of greater than 30 s.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Transport and metabolism of D-[3H]adenosine and L-[3H]adenosine in rat cerebral cortical synaptoneurosomes. 156 Feb 27

Adenosine produced from 5'-AMP has been proposed as a mediator of intrinsic renal regulation. The rates of 5'-AMP and adenosine metabolism are dependent on the activities of enzyme involved in purine metabolism. The activities of adenosine kinase (AK), adenosine deaminase (ADA), 5'-nucleotidase (5'-NT), AMP deaminase, xanthine oxidase and purine nucleoside phosphorylase were measured in cytosolic and membrane fractions from glomeruli, cortical tubules, medullary thick ascending limb of Henle (MTAL) and collecting duct prepared from rat kidney by combinations of sieving and sucrose density gradient centrifugation techniques. In the cytoplasm of glomeruli cells, the activity ratios of ADA/AK and AMP deaminase/5'-NT were 70 and 2.4, respectively. The highest activity of 5'-NT was found in membrane fractions of cortical tubules where it was equally distributed between luminal and antiluminal membranes. Membrane fractions of MTAL did not contain detectable amounts of adenosine deaminase activity. The highest activity of xanthine oxidase and purine nucleoside phosphorylase was in the cytoplasm fraction of glomeruli. These results suggest that deamination of AMP and adenosine may be favored in the cytoplasm of glomeruli cells. In contrast, in the extracellular space of glomeruli and especially in the cortical tubule, AMP can be converted preferentially to adenosine by 5'-NT.
...
PMID:The distribution of enzymes involved in purine metabolism in rat kidney. 161 Aug 88

A series of 6-alkylaminopurine arabinosides were synthesized and found to inhibit varicella-zoster virus (VZV). The antiviral activities of these nucleosides were limited to VZV. None of the other viruses tested in the herpesvirus family were affected. The in vitro antiviral potencies of the 18 arabinosides correlated with their efficiencies as substrates of the VZV-encoded thymidine kinase in all but one case. The arabinosides of 6-methylaminopurine and 6-dimethylaminopurine were the most potent analogs, with 50% inhibitory concentrations against VZV of 3 and 1 microM, respectively. They were not cytotoxic to uninfected MRC-5 cells, human Detroit 98 cells, or mouse L cells (50% inhibitory concentration, greater than 100 microM). Neither 6-methylaminopurine arabinoside nor 6-dimethylaminopurine arabinoside was detectably phosphorylated by either adenosine kinase or 2'-deoxycytidine kinase. These two alkylaminopurine arabinosides were also resistant to deamination catalyzed by adenosine deaminase. The VZV-dependent phosphorylation of these nucleosides offers the possibility of a potent and highly selective therapy for VZV infection.
...
PMID:6-N-substituted derivatives of adenine arabinoside as selective inhibitors of varicella-zoster virus. 165 62


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

---