Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The anti-human immunodeficiency virus agents 2',3'-dideoxyadenosine (ddAdo) and 2'-beta-fluoro-2',3'-dideoxyadenosine (2'-beta-F-ddAdo) are rapidly converted, both in vitro and in vivo, to the corresponding inosine analogs by the widely distributed enzyme adenosine deaminase (EC 3.5.4.4). We have determined the effects of the potent adenosine deaminase inhibitor 2'-deoxycoformycin (2'-dCF) on ddAdo and 2'-beta-F-ddAdo metabolism in MOLT-4 cells and on ddAdo antiviral activity in the ATH8 test system. At levels as low as 5 nM in the incubation medium, 2'-dCF effectively blocks the extracellular deamination of both agents, thus permitting their rapid cellular uptake as the unchanged parent compounds, rather than as the less lipid-soluble 2',3'-dideoxyinosine or 2'-beta-fluoro-2',3'-dideoxyinosine. The result is a significant increase in intracellular levels of the pharmacologically active forms 2',3'-dideoxyadenosine-5'-triphosphate and 2'-beta-fluoro-2',3'-dideoxyadenosine-5'-triphosphate. The effect becomes maximal over the range of 50-250 nM 2'-dCF and declines to control levels when extracellular 2'-dCF levels exceed 1 microM. This decrease in ddAdo and 2'-beta-F-ddAdo phosphorylation with higher levels of the inhibitor appears to result from intracellular penetration of 2'-dCF and consequent inhibition of intracellular deamination, a critical step in the activation of both agents through the 5'-nucleotidase pathway. In anti-human immunodeficiency virus assays, a 2.2-fold increase in ddAdo antiviral potency was seen at 2'-dCF levels of 20 and 50 nM.
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PMID:Enhancement by 2'-deoxycoformycin of the 5'-phosphorylation and anti-human immunodeficiency virus activity of 2',3'-dideoxyadenosine and 2'-beta-fluoro-2',3'-dideoxyadenosine. 796 62

Selective inhibitors of adenosine production, degradation and transport were used to potentiate in vivo levels of adenosine and to determine the source of both basal and N-methyl-D-aspartate (NMDA)-induced increases in levels of endogenous adenosine in vivo. Male Sprague-Dawley rats receiving unilateral intrastriatal injections of pharmacological agents were sacrificed 15 min postinjection by high-energy focused microwave irradiation (10 kW, 1.25 s). Ipsilateral and contralateral striata were dissected, and adenosine levels were measured by high-performance liquid chromatography. Inhibition of 5'-nucleotidase by alpha, beta-methylene ADP dose-dependently decreased adenosine levels under basal as well as NMDA-stimulated conditions. Inhibition of nucleoside transport by dilazep and adenosine deaminase by 2'-deoxycoformycin each dose-dependently increased basal adenosine levels. 2'-Deoxycoformycin potentiated NMDA-induced increases in adenosine levels. Inhibition of adenosine kinase by 5'-amino-5'-deoxyadenosine increased basal levels of adenosine, but did not significantly affect NMDA-induced increases in adenosine. 2'-Deoxycoformycin combined with 5'-amino-5'-deoxyadenosine produced a greater enhancement of NMDA-induced increases in levels of adenosine than when either drug was administered separately. Endogenous adenosine in vivo apparently originates from release of adenosine as well as from release and extracellular breakdown of a nucleotide under both basal and NMDA-stimulated conditions. Furthermore, inhibitors of adenosine kinase and adenosine deaminase work best to increase levels of endogenous adenosine under basal and NMDA-stimulated conditions, respectively.
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PMID:Levels of endogenous adenosine in rat striatum. II. Regulation of basal and N-methyl-D-aspartate-induced levels by inhibitors of adenosine transport and metabolism. 958 May 99