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:3.5.4.17 (adenosine deaminase)
5,206 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

S-Adenosylhomocysteine (SAH) hydrolase was purified 25-fold from bakers' yeast by chemical methods and column chromatography. The purified enzyme could readily synthesize SAH from adenosine and homocysteine, but could hydrolyze only negligible amounts of SAH. The purified enzyme showed no activity towards S-adenosylmethionine, methylthioadenosine, or adenosine. Several nucleotides, sulfhydryl compounds, and ribose could not replace adenosine or homocysteine in the reaction mixture. SAH could be hydrolyzed by SAH hydrolase if commercial adenosine deaminase was included in the reaction mixture. Under these conditions l-homocysteine could act as a product inhibitor. A number of compounds structurally similar to adenosine and homocysteine were found to inhibit synthesis of SAH from adenosine and homocysteine. The strongest inhibitors were adenine, adenosine-3'-monophosphate, adenosine-2'-monophosphate, adenosine diphosphate, adenosine triphosphate, and adenosine-5'-monophosphate. The biosynthetic and hydrolytic activity of SAH hydrolase in yeast cell ghosts was similar to the activity of the enzyme in vitro.
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PMID:Partial purification and characterization of S-adenosylhomocysteine hydrolase isolated from Saccharomyces cerevisiae. 456 9

1. A method is described for detecting and determining the products of metabolism of ADP added to plasma at initial concentrations of about 1mum-ADP. 2. ATP, ADP, AMP, adenosine, inosine and hypoxanthine were detected in human platelet-rich plasma after incubation with ADP and in the presence of either heparin or heparin-citrate. 3. The products of incubation of ADP with human platelet-poor plasma in the presence of heparin were the same as with platelet-rich plasma, except that, when the initial concentration of ADP was 1.5mum, little or no ATP was detected. 4. The ATP detected in platelet-rich plasma when 1.5mum-ADP was initially incubated was present in the platelets and not in the plasma. 5. The time for 50% decay of ADP in either platelet-rich or platelet-poor plasma in the presence of heparin was about 20min. when the initial concentration of ADP was 200mum, but was 6-9min. when the initial ADP concentration was 1.5-2.5mum. The corresponding values in the presence of heparin-citrate were about 45min. and about 9-12min. respectively. 6. Hypoxanthine accumulated to a greater extent in platelet-rich than in platelet-poor plasma after the addition of ADP. 7. After incubation for 15-20min. of either platelet-rich plasma or suspensions of washed platelets in saline with adenosine at an initial concentration of about 3-4mum, ATP, ADP and AMP were detected in the platelets. Similar incubations of washed platelets with inosine also showed the formation of these substances, but to a much less extent. 8. After the addition of adenosine to suspensions of washed platelets in saline, inosine and hypoxanthine were detected in the incubation mixture. After the addition of inosine, hypoxanthine was detected. 9. When ADP at an initial concentration of 1.5mum was added to platelet-rich plasma containing adenosine deaminase, no adenosine was detected in the incubation mixture. There was no difference in the rate of decay of ADP in the presence or absence of the deaminase, but ATP formation was decreased in its presence.
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PMID:Detection and determination of adenosine diphosphate and related substances in plasma. 594 46

In the transversely cut rat hippocampus, adenosine caused a dose-dependent increase in the accumulation of [3H]cyclic AMP from [3H]ATP. Adenosine breakdown products were inactive. AMP was somewhat less effective than adenosine, and its effect could be partially, but not completely, abolished by alpha, beta-methylene-ADP and GMP, which inhibited its metabolism by 5'-nucleotidase. The effect of adenosine was unaffected by inhibitors of adenosine deaminase, but enhanced by several inhibitors of adenosine uptake. Some analogues of adenosine, including N6-phenylisopropyladenosine (PIA), 2-chloroadenosine and adenosine 5'-ethylcarboxamide (NECA), were more active than adenosine, whereas others such as 2-deoxyadenosine and 9-(tetrahydro-2-furyl)adenine (SQ 22536) actually inhibited the response. The effect of PIA was highly stereospecific. The action of adenosine was inhibited by several alkylxanthines, the most potent of which was 8-phenyltheophylline. [3H]Cyclohexyladenosine (CHA) bound specifically to cell membranes from the rat hippocampus. The extent of binding was similar to that found in other cortical areas. The relative potency of some adenosine analogues and alkylxanthines to displace labelled CHA was essentially similar to their potency as effectors of the cyclic AMP system. Adenosine contributed to the cyclic AMP-elevating effect of alpha-adrenoceptor-stimulating drugs and several amino acids, but not to that seen with isoprenaline. The cyclic AMP increase seen following depolarization was only partially adenosine-dependent. The present results demonstrate that the rat hippocampus contains adenosine receptors mediating cyclic AMP accumulation and that these receptors have similar characteristics to those mediating pyramidal cell depression. Adenosine-induced cyclic AMP accumulation may be used as a biochemical correlate to electrophysiology and as a convenient parameter to assess the influence of drugs on adenosine mechanisms in the rat hippocampus.
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PMID:Adenosine receptors mediating cyclic AMP production in the rat hippocampus. 612 48

The synthesis of fluorescent derivatives of nucleosides and nucleotides, by reaction with isatoic anhydride in aqueous solution at mild pH and temperature, yielding their 3'-O-anthraniloyl derivatives, is here described. The N-methylanthraniloyl derivatives were also synthesized by reaction with N-methylisatoic anhydride. Upon excitation at 330-350 nm these derivatives exhibited maximum fluorescence emission at 430-445 nm in aqueous solution with quantum yields of 0.12-0.24. Their fluorescence was sensitive to the polarity of the solvent; in N,N-dimethylformamide the quantum yields were 0.83-0.93. The major differences between the two fluorophores were the longer wavelength of the emission maximum of the N-methylanthraniloyl group and its greater quantum yield in water. All anthraniloyl derivatives, as well as the N-methylanthraniloyl ones, had virtually identical fluorescent properties, regardless of their base structures. The ATP derivatives showed considerable substrate activity as a replacement of ATP with adenylate kinase, guanylate kinase, glutamine synthetase, myosin ATPase and sodium-potassium transport ATPase. The ADP derivatives were good substrates for creatine kinase and glutamine synthetase (gamma-glutamyl transfer activity). The GMP and adenosine derivatives were substrates for guanylate kinase and adenosine deaminase, respectively. All derivatives had only slightly altered Km values for these enzymes. While more fluorescent in water, the N-methylanthraniloyl derivatives were found to show relatively low substrate activities against some of these enzymes. The results indicate that these ribose-modified nucleosides and nucleotides can be versatile fluorescent substrate analogs for various enzymes.
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PMID:New ribose-modified fluorescent analogs of adenine and guanine nucleotides available as substrates for various enzymes. 613 22

The cytotoxicity of 6-thioguanine and 6-mercaptopurine to cultured lymphoblasts and fibroblasts was strongly antagonized by pretreatment of the cells with 100 microM adenosine. Administration of adenosine 2 hours after the antipurine agent did not cause antagonism. In two rat hepatoma cell lines, adenosine pretreatment did not protect cells from the antipurines. Treatment of lymphoblasts or fibroblasts with 100 microM adenosine gave increases up to 150% in cellular ATP and ADP and decreases greater than 80% in UTP and UDP. In the hepatoma lines, adenine nucleotides did not increase by greater than 45%, and uridine nucleotides did not decrease by greater than 40% following adenosine treatment. The selective protection of the normal cells from 6-thioguanine and 6-mercaptopurine was probably the consequence of phosphoribosylpyrophosphate (PRPP) depletion, since adenosine pretreatment decreased PRPP pools by greater than 90% in the normal cells but by only 30% in the malignant hepatoma cells. In the absence of PRPP the antipurines would not be metabolically activated. The selectivity of the adenosine and antipurine combinations was probably attributable to the low activity of adenosine kinase and high activities of adenosine deaminase and PRPP synthetase characteristic of malignant hepatomas.
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PMID:Biochemical approaches to enhancement of antitumor drug selectivity: selective protection of cells from 6-thioguanine and 6-mercaptopurine by adenosine. 616 56

EG626 (oxagrelate), a specific inhibitor of cyclic AMP phosphodiesterase, produced in vitro a concentration-dependent inhibition of platelet aggregation induced by collagen and ADP in human platelets. When adenosine was added to the platelet rich plasma (PRP) in the presence of a threshold concentration of EG626, the potency of adenosine in inhibiting platelet aggregation was markedly potentiated. This potentiating effect of EG626 proved to be synergistic, but not additive and was accompanied by a marked accumulation of cyclic AMP in the platelets. The antiaggregating and cyclic AMP increasing activities of adenosine were little affected by S-(p-nitrobenzyl)-6-thioguanosine (6TG), an uptake inhibitor of adenosine, or 2'-deoxycoformycin, an inhibitor of adenosine deaminase. The incorporation of adenosine into platelets was abolished by 6TG. These observations indicate that incorporation of adenosine into platelets is not required for inhibition of aggregation or an increase in cyclic AMP and that the site of action of adenosine is probably extracellular. It also appears that the synergistic action by EG626 is not the result of an inhibition of adenosine uptake and/or adenosine deaminase. This speculation is supported in part by the finding that EG626 also potentiates the antiaggregating activity of 2-chloroadenosine. Antiaggregating activity of prostaglandin E1, an activator of adenylate cyclase, was markedly potentiated in combination with EG626. Dibutyryl cyclic AMP showed a time-dependent inhibition of the platelet aggregation, and the inhibitory action was markedly potentiated by EG626. Qualitatively similar results were obtained with another phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX). All these data suggest that the synergistic potentiation of the antiaggregating activity of adenosine by EG626 might be due to the synergistic accumulation of cyclic AMP in the platelets. This action is mediated through activation of adenylate cyclase by adenosine in combination with the inhibition of cyclic AMP phosphodiesterase by EG626.
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PMID:Potentiation of antiaggregating activity of adenosine by a phosphodiesterase inhibitor, EG626 (oxagrelate), in human platelets in vitro. 620 94

The erythrocyte adenosine deaminase, nucleoside phosphorylase, hypoxanthineguanine phosphoribosyltransferase and adenine phosphoribosyltransferase activities and plasma urate concentrations were measured in 20 cases of Down's syndrome and in 20 age- and sex-matched control subjects. The mean erythrocyte adenosine deaminase and adenine phosphoribosyltransferase activities and plasma urate concentrations were significantly higher in Down's syndrome subjects than in controls (p less than 0.001, p less than 0.01 and p less than 0.001, respectively). In all subjects studied there was a positive correlation between the erythrocyte adenosine deaminase activity and plasma urate concentration (r = 0.488, p less than 0.005). The concentrations of the erythrocyte adenine nucleotides, AMP, ADP and ATP, did not differ in Down's syndrome (n = 10) from those of control subjects (n = 10). The results suggest that the increase of plasma urate concentrations is a consequence of the increase in adenosine deaminase activity in Down's syndrome patients.
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PMID:Erythrocyte adenosine deaminase, purine nucleoside phosphorylase and phosphoribosyltransferase activity in patients with Down's syndrome. 621 25

1. The role of adenosine deaminase (EC 3.5.4.4), ecto-(5'-nucleotidase) (EC 3.1.3.5) and ecto-(non-specific phosphatase) in the CN-induced catabolism of adenine nucleotides in intact rat polymorphonuclear leucocytes was investigated by inhibiting the enzymes in situ. 2. KCN (10mM for 90 min) induced a 20-30% fall in ATP concentration accompanied by an approximately equimolar increase in hypoxanthine, ADP, AMP and adenosine concentrations were unchanged, and IMP and inosine remained undetectable ( less than 0.05 nmol/10(7) cells). 3. Cells remained 98% intact, as judged by loss of the cytoplasmic enzyme lactate dehydrogenase (EC 1.1.1.27). 4. Pentostatin (30 microM), a specific inhibitor of adenosine deaminase, completely inhibited hypoxanthine production from exogenous adenosine (55 microM), but did not black CN-induced hypoxanthine production or cause adenosine accumulation in intact cells. This implied that IMP rather than adenosine was an intermediate in AMP breakdown in response to cyanide. 5. Antibodies raised against purified plasma-membrane 5'-nucleotidase inhibited the ecto-(5'-nucleotidase) by 95-98%. Non-specific phosphatases were blocked by 10 mM-sodium beta-glycerophosphate. 6. These two agents together blocked hypoxanthine production from exogenous AMP and IMP (200 microM) by more than 90%, but had no effect on production from endogenous substrates. 7. These data suggest that ectophosphatases do not participate in CN-induced catabolism of intracellular AMP in rat polymorphonuclear leucocytes. 8. A minor IMPase, not inhibited by antiserum, was detected in the soluble fraction of disrupted cells.
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PMID:Role of adenosine deaminase, ecto-(5'-nucleotidase) and ecto-(non-specific phosphatase) in cyanide-induced adenosine monophosphate catabolism in rat polymorphonuclear leucocytes. 624 64

Inorganic pyrophosphate and triphosphate inhibit adenylate deaminase from rat skeletal muscle with K1 values of 10 and 1.5 microM, respectively, in the presence of 150 mM KCl at pH 7. They act by reducing the apparent affinity of the enzyme for AMP, with relatively small effects on Vmax. The inhibitions are diminished by H+, the KI values increasing two- to threefold in going from pH 7.0 to 6.2, and are relieved by ADP. These properties are similar to the inhibitions produced by GTP and ATP, indicating that pyrophosphate and triphosphate act like analogues of the nucleoside triphosphates. Neither of these inhibitors shows relief of inhibition at high concentrations as do ATP and GTP. These results suggest that nucleotides interact with the inhibitor site of the enzyme primarily through their phosphate moieties and with the activator site primarily through their nucleoside moieties. As the concentration of KCl is increased from 25 to 300 mM, the apparent affinities of the enzyme for ATP, GTP, orthophosphate, pyrophosphate, and triphosphate are decreased 8-100-fold. The cooperativity of the inhibitions is increased with the Hill coefficient rising from 1.0 to 1.3-1.8, and the maximum inhibition approaches 100%. Maximum activation by ADP is reduced from 1800% at 25 mM KCl to 80% at 200 mM KCl. Experiments with (CH3)4NCl indicate that activation of the enzyme by KCl involves both specific K+ effects and ionic strength effects.
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PMID:Effects of pyrophosphate, triphosphate, and potassium chloride on adenylate deaminase from rat muscle. 625 52

The endogenous level of cyclic AMP in incubated synaptosomes from cerebral cortex of guinea pigs was investigated after the addition of various agents to the incubation medium. It appeared that the synaptosomal suspension already contained exogenous adenosine. Preincubation with theophylline or with adenosine deaminase (ADase) decreased both the exogenous level of adenosine and the intrasynaptosomal level of cyclic AMP. The level of cyclic AMP was reincreased by the addition of adenosine agonists, especially 2-chloroadenosine. This increase was antagonized by deoxyadenosine and was not inhibited by dipyridamole. These results suggest that the adenosine derivatives in the synaptic cleft regulate the level of cyclic AMP in nerve terminals through adenosine receptor on the presynaptic membrane. ADP, ATP, dopamine, and histamine also stimulate the formation of cyclic AMP in the ADase-treated synaptosomes.
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PMID:Change of cycle AMP level in synaptosomes from cerebral cortex; increase by adenosine derivatives. 625 52


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