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)

We tried some improvement of inosine production using an inosine-producing mutant of Escherichia coli which is deficient in purF (phosphoribosylpyrophosphate (PRPP) amidotransferase gene), purA (succinyl-adenosine 5'-monophosphate (AMP) synthetase gene), deoD (purine nucleoside phosphorylase gene), purR (purine repressor gene) and add (adenosine deaminase gene), and harboring the desensitized PRPP amidotransferase gene as a plasmid. The guaB (inosine 5'-monophosphate (IMP) dehydrogenase gene) disruption brought about a slightly positive effect on the inosine productivity. Alternatively, the gsk (guanosine-inosine kinase gene) disruption caused a considerable amount of guanosine accumulation together with a slight increase in the inosine productivity. The further addition of guaC (guanosine 5'-monophosphate (GMP) reductase gene) disruption did not lead to an increased guanosine accumulation, but brought about the decrease of inosine accumulation.
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PMID:gsk disruption leads to guanosine accumulation in Escherichia coli. 1144 Jan 47

Kinetic parameters (Vmax, Km) of enzymes catalyzing the reaction sequence 5'-AMP-->adenosine-->inosine-->hypoxanthine in rat's blood serum were studied at different postirradiation terms after combined effect of external gamma-irradiation (1 Gy, 137Cs) and incorporated 137Cs (160 kBq). It was shown that radiation-induced changes of kinetic properties of 5'-nucleotidase, adenosine deaminase, purine nucleoside phosphorylase were expressed at earlier terms under combined radiation effect than it occurred at external gamma-irradiation effect only. Postirradiation modification of enzymes kinetics brought about the acceleration of 5'-AMP conversion to its endpoint product, hypoxanthine. Negative consequences of the postirradiation activation of purine metabolism, in particular, the activation of hypoxanthine prooxidant system and the rise of clastogenic activity of blood plasma are discussed.
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PMID:[Post-radiation changes in kinetic parameters of purine-catabolizing enzymes in rat blood serum after combined action of external and internal irradiation caused by 137Cs]. 1145 39

Cyclic adenosine monophosphate (cAMP) has been implicated as an important regulator of meiotic maturation in mammalian oocytes. A decrease in cAMP, brought about by the action of cAMP phosphodiesterase (PDE), is thought to initiate germinal vesicle breakdown (GVB) by the inactivation of cAMP-dependent protein kinase. However, the product of PDE activity, 5'-AMP, is a potent activator of an important regulatory enzyme, AMP-activated protein kinase (AMPK). The aim of this study was to evaluate a possible role for AMPK in meiotic induction, using oocytes obtained from eCG-primed, immature mice. Alpha-1 and -2 isoforms of the catalytic subunit of AMPK were detected in both oocytes and cumulus cells. When 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICA riboside), an activator of AMPK, was tested on denuded oocytes (DO) and cumulus cell-enclosed oocytes (CEO) maintained in meiotic arrest by dbcAMP or hypoxanthine, GVB was dose-dependently induced. Meiotic induction by AICA riboside in dbcAMP-supplemented medium was initiated within 3 h in DO and 4 h in CEO and was accompanied by increased AMPK activity in the oocyte. AICA riboside also triggered GVB when meiotic arrest was maintained with hypoxanthine, 8-AHA-cAMP, guanosine, or milrinone, but was ineffective in olomoucine- or roscovitine-arrested oocytes, indicating that it acts upstream of maturation-promoting factor. Adenosine monophosphate dose-dependently stimulated GVB in DO when meiotic arrest was maintained with dbcAMP or hypoxanthine. This effect was not mimicked by other monophosphate or adenosine nucleotides and was not affected by inhibitors of ectophosphatases. Combined treatment with adenosine and deoxycoformycin, an adenosine deaminase inhibitor, stimulated GVB in dbcAMP-arrested CEO, suggesting AMPK activation due to AMP accumulation. It is concluded that phosphodiesterase-generated AMP may serve as a transducer of the meiotic induction process through activation of AMPK.
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PMID:A potential role for AMP-activated protein kinase in meiotic induction in mouse oocytes. 1196 66

Adenosine kinase was partially purified from wheat germ. This enzyme preparation, which was devoid of adenine phosphoribosyltransferase and nearly free of adenosine deaminase but contained adenylate kinase, rapidly phosphorylated adenosine and a cytokinin, N(6)-(delta(2)-isopentenyl)adenosine. Electrophoretic analysis indicated that only N(6)-(delta(2)-isopentenyl)adenosine-monophosphate was formed from the cytokinin while about 55% AMP, 45% ADP, and a trace of ATP were formed from adenosine. The biosynthesized nucleoside monophosphates were quantitatively hydrolyzed to the corresponding nucleosides by 5'-nucleotidase and the isopentenyl side chain of the phosphorylated cytokinin was not cleaved. The enzyme did not catalyze phosphorylation of inosine.The phosphorylation of the cytokinin and adenosine required ATP and Mg(2+). The pH optimum was from 6.8 to 7.2 for both the cytokinin and adenosine. At pH 7 and 37 C the Km and V(max) for the cytokinin were 31 mum and 8.3 nmoles per mg protein per minute, and the values for adenosine were 8.7 mum and 46 nmoles per mg protein per minute. Crude enzyme preparations from tobacco callus tissue and wheat germ phosphorylated N(6)-(delta(2)-isopentenyl)adenosine. These preparations also phosphorylated N(6)-(delta(2)-isopentenyl)adenine when 5-phosphorylribose-1-pyrophosphate was present.
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PMID:Phosphorylation of cytokinin by adenosine kinase from wheat germ. 1665 70

CD73 (ecto-5'-nucleotidase) on human gingival fibroblasts plays a role in the regulation of intracellular cAMP levels through the generation of adenosine, which subsequently activates adenosine receptors. In this study, we examined the involvement of ecto-adenosine deaminase, which can be anchored to CD26 on human gingival fibroblasts, in metabolizing adenosine generated by CD73, and thus attenuating adenosine receptor activation. Ecto-adenosine deaminase expression on fibroblasts could be increased by pre-treatment with a lysate of Jurkat cells, a cell line rich in cytoplasmic adenosine deaminase. Interestingly, the cAMP response to adenosine generated from 5'-AMP via CD73 and the ability of 5'-AMP to induce hyaluronan synthase 1 mRNA were significantly decreased by the pre-treatment of fibroblasts with Jurkat cell lysate. This inhibitory effect was reversed by the specific adenosine deaminase inhibitor. These results suggest that ecto-adenosine deaminase metabolizes CD73-generated adenosine and regulates adenosine receptor activation.
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PMID:Activation of adenosine receptor on gingival fibroblasts. 1686 Dec 92

Bacterial tRNA-specific adenosine deaminase (TadA) catalyzes the essential deamination of adenosine to inosine at the wobble position of tRNAs and is necessary to permit a single tRNA species to recognize multiple codons. The transition state structure of Escherichia coli TadA was characterized by kinetic isotope effects (KIEs) and quantum chemical calculations. A stem loop of E. coli tRNA(Arg2) was used as a minimized TadA substrate, and its adenylate editing site was isotopically labeled as [1'-(3)H], [5'-(3)H2], [1'-(14)C], [6-(13)C], [6-(15)N], [6-(13)C, 6-(15)N] and [1-(15)N]. The intrinsic KIEs of 1.014, 1.022, 0.994, 1.014 and 0.963 were obtained for [6-(13)C]-, [6-(15)N]-, [1-(15)N]-, [1'-(3)H]-, [5'-(3)H2]-labeled substrates, respectively. The suite of KIEs are consistent with a late SNAr transition state with a complete, pro-S-face hydroxyl attack and nearly complete N1 protonation. A significant N6-C6 dissociation at the transition state of TadA is indicated by the large [6-(15)N] KIE of 1.022 and corresponds to an N6-C6 distance of 2.0 A in the transition state structure. Another remarkable feature of the E. coli TadA transition state structure is the Glu70-mediated, partial proton transfer from the hydroxyl nucleophile to the N6 leaving group. KIEs correspond to H-O and H-N distances of 2.02 and 1.60 A, respectively. The large inverse [5'-(3)H] KIE of -3.7% and modest normal [1'-(3)H] KIE of 1.4% indicate that significant ribosyl 5'-reconfiguration and purine rotation occur on the path to the transition state. The late SNAr transition-state established here for E. coli TadA is similar to the late transition state reported for cytidine deaminase. It differs from the early SNAr transition states described recently for the adenosine deaminases from human, bovine, and Plasmodium falciparum sources. The ecTadA transition state structure reveals the detailed architecture for enzymatic catalysis. This approach should be readily transferable for transition state characterization of other RNA editing enzymes.
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PMID:Transition state structure of E. coli tRNA-specific adenosine deaminase. 1825 77

It has been known for a long time that inhaled adenosine-monophosphate (AMP) induces airway obstruction in asthmatic patients, but not in healthy subjects. The mechanism of AMP is indirect and occurs via its decay product, adenosine. It stimulates mast cells through its low-affinity receptor A2B to release histamine, which ultimately leads to smooth muscle contraction. This feature of adenosine reveals its pro-inflammatory function, which may play important role in asthma. Indeed, mice lacking adenosine deaminase (ADA), an enzyme which decomposes adenosine, develop asthma-like disorder with elevated IgE, eosinophilia and airway hyperresponsiveness. Human studies showed elevated adenosine levels in bronchoalveolar lavage and exhaled breath condensate of asthmatics as compared to healthy people. Furthermore, certain human ADA phenotypes are associated with prevalence of asthma. These data suggest a protective role for ADA and a pro-inflammatory function for adenosine in asthma. The role of adenosine in inflammatory processes, however, is not unequivocal. Some in vitro studies showed that adenosine binding to its high-affinity receptor A2A results in inhibition of leukotriene synthesis or function of adhesion molecules. It is possible that the concentration of adenosine in lung tissues determines whether it promotes or reduces inflammation. Adenosine has also been associated with other respiratory diseases such as fibrosis, sarcoidosis, cystic fibrosis or tuberculosis. Identification of adenosine receptor subtypes and their role in the pathomechanism of respiratory diseases may provide new therapeutical targets. This review aims to summarize the role of adenosine and adenosine receptors in asthma and other pulmonary disorders.
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PMID:Adenosine and adenosine receptors in the pathomechanism and treatment of respiratory diseases. 1847 99

Cytosolic enzymes AMP deaminase and adenosine deaminase (ADA) catalyze AMP and adenosine deamination, constitute rate-limiting steps of adenine nucleotide catabolism and play important roles in cellular energy metabolism. In this study, AMP deaminase and ADA activities of rat liver, neocortex, cerebellum, striatum and hippocampus were investigated in acute ammonia intoxication and subacute CCl(4)-induced hepatitis. Activities of both AMP deaminase and ADA in the liver were elevated by 2.4-4.2-fold (p<0.0001) in both models of hepatotoxic injury as compared with controls. In acute hyperammonemia activities of AMP, deaminase and ADA increased by 46-59% (p<0.02) in the neocortex and did not change in the striatum. In the hippocampus of hyperammonemic rats, only AMP deaminase activity was increased by 48% (p=0.0004), and in the cerebellum only ADA activity was increased significantly (by 26%, p<0.05). The adenylate pool size and energy charge were greatly reduced in the neocortex of hyperammonemic rats. Results suggested that two parallel pathways of AMP breakdown, including AMP deaminase and ADA, respectively, are up-regulated under pathological conditions, probably in order to overcome compensatory synthesis of adenylates, to ensure prompt adenylate pool depletion and reduce the adenylate energy charge in liver and selected brain regions.
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PMID:AMP deaminase and adenosine deaminase activities in liver and brain regions in acute ammonia intoxication and subacute toxic hepatitis. 1990 Apr 20

This study investigated the biochemical relationship between human follicular/oocyte maturity and the levels of follicular fluid purines. Intrafollicular levels of purine metabolites and creatinine are associated with oocyte presence, and the presence of such high levels of adenosine indicates a privileged site with no adenosine deaminase activity. Subgrouping according to oocyte recovery and fertilization revealed differences in correlation between the purine metabolites: Only where an oocyte was recovered and subsequently fertilized did follicular fluid adenosine, adenine, and hypoxanthine levels correlate with each other. Significantly, purines' correlation with levels of the terminal degradation product, uric acid, could only be seen in failed fertilization samples. Given the established metabolic pathways for adenosine triphosphate/adenosine diphosphate/adenosine monophosphate degradation, the results indicate maximization of 2 purine salvage pathways (from adenine and hypoxanthine) that pivot on the presence of high adenosine levels. Such optimized recovery may be necessary to build a store of salvaged adenosine phosphate for oocyte survival.
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PMID:High follicular fluid adenosine levels may be pivotal in the metabolism and recycling of adenosine nucleotides in the human follicle. 2049 75

Abnormal growth of glomerular mesangial cells (GMCs) contributes to the pathophysiology of many types of nephropathy. Because adenosine is an autocrine/paracrine factor that potentially could regulate GMC proliferation and because the extracellular 3',5'-cAMP-adenosine pathway (i.e., the conversion of extracellular 3',5'-cAMP to 5'-AMP and adenosine on the cell surface) could generate adenosine in the biophase of GMC receptors, we investigated the role of the 3',5'-cAMP-adenosine pathway in modulating growth [cell proliferation, DNA synthesis ([(3)H]thymidine incorporation), collagen synthesis ([(3)H]proline incorporation), and mitogen-activated protein kinase activity] of GMCs. The addition of exogenous 3',5'-cAMP to human GMCs increased extracellular levels of 5'-AMP, adenosine, and inosine, and 3-isobutyl-1-methylxanthine (phosphodiesterase inhibitor), 1,3-dipropyl-8-p-sulfophenylxanthine (ecto-phosphodiesterase inhibitor), and alpha,beta-methylene-adenosine-5'-diphosphate (ecto-5'-nucleotidase inhibitor) attenuated the increases in adenosine and inosine. Forskolin augmented extracellular 3',5'-cAMP and adenosine concentrations, and 2',5'-dideoxyadenosine (adenylyl cyclase inhibitor) blocked these increases. Exogenous 3',5'-cAMP and forskolin inhibited all indices of cell growth, and antagonism of A(2) [(E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine, KF17837] or A(1)/A(2) (1,3-dipropyl-8-p-sulfophenylxanthine, DPSPX), but not A(1) (8-cyclopentyl-1,3-dipropylxanthine), or A(3){N-(2-methoxyphenyl)-N'-[2-(3-pyridinyl)-4-quinazolinyl]-urea, VUF5574}, adenosine receptors blocked the growth-inhibitory actions of exogenous 3',5'-cAMP, but not the effects of 8-bromo-3',5'-cAMP (stable 3',5'-cAMP analog). Erythro-9-(2-hydroxy-3-nonyl)adenine (adenosine deaminase inhibitor) plus 5-iodotubercidin (adenosine kinase inhibitor) enhanced the growth inhibition by exogenous 3',5'-cAMP and forskolin, and A(2) receptor antagonism blocked this effect. In rat GMCs, down-regulation of A(2B) receptors with antisense, but not sense or scrambled, oligonucleotides abrogated the inhibitory effects of 3',5'-cAMP and forskolin on cell growth. The extracellular 3',5'-cAMP-adenosine pathway exists in GMCs and attenuates cell growth via A(2B) receptors. Pharmacological augmentation of this pathway could abate pathological glomerular remodeling.
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PMID:Extracellular 3',5'-cAMP-adenosine pathway inhibits glomerular mesangial cell growth. 2019 27


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