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)

Adenosine has been implicated as an important endogenous regulator of various tissue functions. In diabetes, the responsiveness of several tissues to adenosine is altered. The aim of this study was to investigate the activities of enzymes metabolizing adenosine in tissues of diabetic rats. The cytosolic activity (V(max)) of adenosine kinase (AK) was decreased by 50% in the kidney and by 40% in the heart and liver of diabetic rats. A decrease in the V(max) of AK in diabetic tissues was not associated with a change in the K(m) for adenosine. Evaluation of AK gene transcript status showed significantly lower levels of AK mRNA in diabetic tissues as compared to normal tissues. In diabetic kidneys, the level of AK gene transcript was lowered by 50% on first day after streptozotocin administration, and these reduced levels were sustained declined during the next 10 days. Smaller changes in AK gene transcript levels were observed in the heart and liver than in the kidney. The cytosolic activities of 5'-nucleotidase, AMP deaminase, and adenosine deaminase were unchanged in kidney, heart, and liver of diabetic rats. These results suggest that the turnover of the AMP-adenosine metabolic cycle might be impaired in diabetic tissues due to the reduced activity of adenosine kinase.
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PMID:Decreased expression of adenosine kinase in streptozotocin-induced diabetes mellitus rats. 1068 43

N3-Substituted coformycin aglycon analogues with improved AMP deaminase (AMPDA) inhibitory potency are described. Replacement of the 5-carboxypentyl substituent in the lead AMPDA inhibitor 3-(5-carboxypentyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1, 3]diazepin-8-ol (2) described in the previous article with various carboxyarylalkyl groups resulted in compounds with 10-100-fold improved AMPDA inhibitory potencies. The optimal N3 substituent had m-carboxyphenyl with a two-carbon alkyl tether. For example, 3-[2-(3-carboxy-5-ethylphenyl)ethyl]-3,6,7,8-tetrahydroimidazo[4, 5-d][1,3]diazepin-8-ol (43g) inhibited human AMPDA with a K(i) = 0. 06 microM. The compounds within the series also exhibited >1000-fold specificity for AMPDA relative to adenosine deaminase.
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PMID:AMP deaminase inhibitors. 3. SAR of 3-(carboxyarylalkyl)coformycin aglycon analogues. 1078 Sep 7

Adenosine, through activation of membrane-bound receptors, has been reported to have neuroprotective properties during strokes or seizures. The role of astrocytes in regulating brain interstitial adenosine levels has not been clearly defined. We have determined the nucleoside transporters present in rat C6 glioma cells. RT-PCR analysis, (3)H-nucleoside uptake experiments, and [(3)H]nitrobenzylthioinosine ([(3)H]NBMPR) binding assays indicated that the primary functional nucleoside transporter in C6 cells was rENT2, an equilibrative nucleoside transporter (ENT) that is relatively insensitive to inhibition by NBMPR. [(3)H]Formycin B, a poorly metabolized nucleoside analogue, was used to investigate nucleoside release processes, and rENT2 transporters mediated [(3)H]formycin B release from these cells. Adenosine release was investigated by first loading cells with [(3)H]adenine to label adenine nucleotide pools. Tritium release was initiated by inhibiting glycolytic and oxidative ATP generation and thus depleting ATP levels. Our results indicate that during ATP-depleting conditions, AMP catabolism progressed via the reactions AMP --> IMP --> inosine --> hypoxanthine, which accounted for >90% of the evoked tritium release. It was surprising that adenosine was not released during ATP-depleting conditions unless AMP deaminase and adenosine deaminase were inhibited. Inosine release was enhanced by inhibition of purine nucleoside phosphorylase; ENT2 transporters mediated the release of adenosine or inosine. However, inhibition of AMP deaminase/adenosine deaminase or purine nucleoside phosphorylase during ATP depletion produced release of adenosine or inosine, respectively, via the rENT2 transporter. This indicates that C6 glioma cells possess primarily rENT2 nucleoside transporters that function in adenosine uptake but that intracellular metabolism prevents the release of adenosine from these cells even during ATP-depleting conditions.
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PMID:Purine uptake and release in rat C6 glioma cells: nucleoside transport and purine metabolism under ATP-depleting conditions. 1098 33

Nucleosides and nucleotides which are able to undergo covalent hydration in the aglycone ring system are potential inhibitors of the enzymes adenosine deaminase (ADA) and AMP deaminase, respectively. Calculations of the enthalpy of covalent hydration and of enzyme binding energy have been used to design new inhibitors of ADA. The ribosyl triazolotriazine 16, which was synthesized as a result of these calculations, exists predominantly as the covalent hydrate 18 in water and is a potent inhibitor of mammalian ADA (IC(50) 50 nM).
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PMID:Design and synthesis of inhibitors of adenosine and AMP deaminases. 1126 95

A cDNA coding for a protein with significant similarity to adenosine deaminase (ADA) was found while randomly sequencing a cDNA library constructed from salivary gland extracts of adult female Culex quinquefasciatus. Prompted by this result, we found high ADA activities in two culicine mosquitoes, Culex quinquefasciatus and Aedes aegypti, but not in the anopheline Anopheles gambiae. Homogenates from Culex quinquefasciatus also have an AMP deaminase activity that is three times greater than the ADA activity, whereas in Aedes aegypti the AMP deaminase activity is less than 10% of the ADA activity. Evidence for secretion of ADA during blood feeding by Aedes aegypti includes the presence of ADA activity in warm solutions probed through a membrane by mosquitoes and in serotonin-induced saliva and a statistically significant reduction in the levels of the enzyme in Aedes aegypti following a blood meal. We could not demonstrate, however, that C. quinquefasciatus secrete ADA in their saliva. Male Aedes aegypti and C. quinquefasciatus, which do not feed on blood, have less than 3% of the levels of ADA found in females. We propose that ADA activity in A. aegypti may help blood feeding by removing adenosine, a molecule associated with both the initiation of pain perception and the induction of mast cell degranulation in vertebrates, and by producing inosine, a molecule that potently inhibits the production of inflammatory cytokines. The role of salivary ADA in Culex quinquefasciatus remains unclear.
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PMID:The salivary adenosine deaminase activity of the mosquitoes Culex quinquefasciatus and Aedes aegypti. 1144 Oct 41

The dry powdered of Sinapis arvensis, Thymelaea hirsuta, Callistemon lanceolatus and Peganum harmala showed molluscicidal activity against Biomphalaria alexandrina, specific intermediate hosts to Schistosoma mansoni. Effect of LC25 of dry powdered plant molluscicides on hexokinase (HK), glucose phosphate isomerase (GPI), AMP deaminase, adenosine deaminase and phenol oxidase (PO) of B. alexandrina was traced. C. lanceolatus showed the highest molluscicidal activity as it has the lowest LC50 compared to S. arvensis, T. hirsuta, and P. harmala. LC25 of the latter three plants resulted in more significant inhibition of HK, GPI, AMP-deaminase and PO than C. lanceolatus. Treatment of snails with LC10 of these plants markedly affected compatibility of B. alexandrina to S. mansoni infection. Significant decrease in cercarial production recorded in snails treated with sublethal concentrations of S. arvensis, T. hirsuta, and P. harmala. Remarkable impairment of the egg laying capacity of molluscicide-treated snails was also recorded. Correlation between activity levels of HK, GPI and AMP deaminase and compatibility to parasitic infection and role of PO in the egglaying capacity of these snail species were discussed.
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PMID:In vivo, attenuation of schistosome cercarial development and disturbance of egg laying capacity in Biomphalaria alexandrina using sublethal concentrations of plant molluscicides. 1177 93

It has been established, that the total X-ray irradiation of animals takes influence upon the functional activity of key enzymes of adenine nucleotides metabolism: adenylatekinase, AMP deaminase, 5'-nucleotidase, adenosine deaminase and purine nucleoside phosphorylase in rat's thymocytes. The increase of activity of the investigated enzymes is observed in our experiment, except 5'-nucleotidase, which activity is authentically decreasing after irradiation (1.0 and 7.78 Gy). The injection of the preparation riboxine to experimental animals 15 min prior to the exposure has normalized the purine exchange enzymes activity.
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PMID:[Activity of purine enzyme metabolism in rat thymocytes after irradiation and after administration of riboxine]. 1457 81

Human purine nucleoside phosphorylase (PNP) is a ubiquitous enzyme which plays a key role in the purine salvage pathway, and PNP deficiency in humans leads to an impairment of T-cell function, usually with no apparent effect on B-cell function. PNP is highly specific for 6-oxopurine nucleosides and exhibits negligible activity for 6-aminopurine nucleosides. The catalytic efficiency for inosine is 350,000-fold greater than for adenosine. Adenine nucleosides and nucleotides are deaminated by adenosine deaminase and AMP deaminase to their corresponding inosine derivatives which, in turn, may be further degraded. Here we report the crystal structures of human PNP in complex with inosine and 2('),3(')-dideoxyinosine, refined to 2.8A resolution using synchrotron radiation. The present structures provide explanation for ligand binding, refine the purine-binding site, and can be used for future inhibitor design.
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PMID:Structures of human purine nucleoside phosphorylase complexed with inosine and ddI. 1470 28

Blood lymphocyte activities of 5'-nucleotidases, adenosine deaminase and AMP deaminase have been investigated for evaluation of immune system state of albino rats under normal conditions, immobilization stress and effect of radiation. Stress-induced reactions were characterized by changes of activities of these enzymes. However the ratios of activities 5'- nucleotidase/AMP-deaminase (coefficient A) and adenosine-deaminase/AMP-deaminase (coefficient B) were even more informative than separate analysis of these enzymes.
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PMID:[Enzymes of purine nucleotide metabolism in assessment of the functional competence of the immune system]. 1594 54

Adenosine deaminase (ADA) is a well-characterized enzyme involved in the depletion of adenosine levels. A group of proteins with similarity to ADA, the adenosine deaminase-related growth factors (ADGF; known as CECR1 in vertebrates), has been described recently in various organisms. We have determined the phylogenetic relationships of various gene products with significant amino acid similarity to ADA using parsimony and Bayesian methods, and discovered a novel paralogue, termed ADA-like (ADAL). The ADGF proteins share a novel amino acid motif, "MPKG," within which the proline and lysine residues are also conserved in the ADAL and ADA subfamilies. The significance of this new domain is unknown, but it is located just upstream of two ADA catalytic residues, of which all eight are conserved among the ADGF and ADAL proteins. This conservation suggests that ADGF and ADAL may share the same catalytic function as ADA, which has been proven for some ADGF members. These analyses also revealed that some genes previously thought to be classic ADAs are instead ADAL or ADGFs. We here define the ADGF, ADAL, ADA, adenine deaminase (ADE), and AMP deaminase (AMPD) groups as subfamilies of the adenyl-deaminase family. The availability of genomic data for the members of this family allowed us to reconstruct the intron evolution within the phylogeny and strengthen the introns-late hypothesis of the synthetic introns theory. This study shows that ADA activity is clearly more complex than once thought, perhaps involving a delicately balanced pattern of temporal and spatial expression of a number of paralogous proteins.
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PMID:Phylogenetic analysis reveals a novel protein family closely related to adenosine deaminase. 1624 11


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