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:3.1.3.5 (5'-nucleotidase)
3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tick Boophilus microplus contains a nucleoside phosphate-hydrolysing enzyme which, in many respects, resembles the well characterized 5'-nucleotidase from mammalian tissue. The tick enzyme has been purified to homogeneity. It is a membrane-bound glycoprotein with an apparent Mr of 67,000 and, although it fails to hydrolyse a range of nucleoside 2'- or 3'-monophosphates, it has broad specificity for the 5' derivatives. Further investigation of the enzyme's substrate specificity, however, shows some important differences from the mammalian nucleotidases. It hydrolyses both bis-p-nitrophenyl phosphate and p-nitrophenyl phenylphosphonate, typical substrates for phosphodiesterases. However, the tick enzyme is most strikingly different from the mammalian enzymes in that it hydrolyses not only AMP but ADP and ATP as well. Further, the products of the hydrolysis of ATP are adenosine and tripolyphosphate, a reaction which has not been reported previously. The products of ADP hydrolysis are adenosine and pyrophosphate.
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PMID:Purification and properties of a novel nucleotide-hydrolysing enzyme (5'-nucleotidase) from Boophilus microplus. 253 5

In view of its vasodilatory effect on the coronary circulation (probably mediated by adenosine) and its metabolic compartmentalization (intramitochondrial activation to form acetyl-CoA), the metabolic effects of acetate were studied in isolated rat heart mitochondria. Acetate caused conversion of adenylates to AMP and the formation of adenosine. Adenylate efflux was inhibited by carboxyatractyloside but not by N-ethylmaleimide. The intramitochondrial accumulation of AMP was enhanced by carboxyatractyloside during acetate metabolism and the formation of extramitochondrial adenosine inhibited. A carboxyatractyloside-sensitive unidirectional AMP influx with a Km of 50 microM and Vmax of 11 nmol/min per mg mitochondrial protein was also observed. The mitochondrial adenosine content was high and constant during the experiments. The steep apparent concentration gradient of adenosine indicates that most of the mitochondrial adenosine is tightly bound to protein. Adenosine formation was proportional to the extramitochondrial AMP concentration, showing that the 5'-nucleotidase activity of cardiac mitochondrial preparations is extramitochondrial in origin. The data suggest that the mitochondrial ATP/ADP carrier is capable of transporting AMP and that intramitochondrial AMP is recycled during acetate metabolism in the myocardium partially by means of the ATP/ADP translocator, leading to an increase in extramitochondrial AMP and adenosine formation.
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PMID:Adenine nucleotide transport and adenosine production in isolated rat heart mitochondria during acetate metabolism. 254 56

We have used the rat isolated, perfused heart to study the metabolism of adenine nucleotides on a single passage through the coronary circulation. Low doses (3-30 nmol) of ATP, ADP, or AMP injected as a bolus were extensively catabolized by ectoenzymes. Increasing doses of each nucleotide demonstrated saturability of catabolism that occurred at significantly lower doses of AMP than of ADP or ATP. The patterns of catabolites formed in each case were consistent with the major pathway of metabolism being sequential dephosphorylation of ATP----ADP----AMP----adenosine, although from experiments in which [3H]ATP was co-injected with unlabeled ADP, it appears that some direct conversion of ATP----AMP can occur. Furthermore, particularly in the presence of excess unlabeled ATP, [3H]ADP was phosphorylated to [3H]ATP, indicating that ectoenzymes capable of interconverting nucleotides are present. By evaluating recovery and metabolism in serial samples collected rapidly after bolus injection, we were able to use the integrated form of the Michaelis-Menten equation as developed by Bronikowski et al. (Math. Biosci. 61: 237-266, 1982) to derive Michaelis constant (Km) and maximum velocity times capillary plasma volume (Amax) values for adenosinetriphosphatase, adenosine diphosphatase, and 5'-nucleotidase (450, 300, and 93 microM; and 5.3, 5.9, and 1.7 mumol/min, respectively). This analysis also indicated that there is a high degree of heterogeneity of path lengths within the coronary circulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetics of adenine nucleotide catabolism in coronary circulation of rats. 254 8

Glycerate 2,3-bisphosphate, a potent stimulator of the cytosolic 5'-nucleotidase which preferentially hydrolyzes IMP and GMP in human erythrocytes (Bontemps et al., 1988, Biochem. J. 250, 687-696), also stimulates the dephosphorylation of IMP in cytosol fractions of rat heart, liver, brain, kidney, spleen and erythrocytes, and of human polymorphonuclear leucocytes, mixed peripheral blood lymphocytes, platelets and fibroblasts. Depending on the cell type, stimulation by 5 mM glycerate 2,3-bisphosphate varied from 1.5- to 12-fold. Where investigated, glycerate 2,3-bisphosphate had an approx. 5-fold higher affinity for the enzyme than its other stimulator, ATP. These observations provide a useful tool to distinguish IMP-GMP 5'-nucleotidase from other 5'-nucleotidases, and suggest a common origin of the cytosolic IMP-GMP 5'-nucleotidase in various tissues.
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PMID:Stimulation by glycerate 2,3-bisphosphate: a common property of cytosolic IMP-GMP 5'-nucleotidase in rat and human tissues. 254 5

Membrane-bound 5'-nucleotidase from Vibrio parahaemolyticus was solubilized and purified using a nonionic detergent, heptyl-beta-D-thioglucoside, and was characterized. This enzyme required Mg2+ for activity, maximum activity being observed at 5 and 20 mM Mg2+ with AMP and ATP, respectively, as substrates. Of the divalent cations tested, Mn2+ and Co2+ were able to replace Mg2+ partially, whereas Ca2+ was ineffective. Zinc strongly inhibited the enzyme activity and Ni2+ caused partial inhibition. This enzyme required Cl- for activity, the optimal concentration being 20 mM or more. The order of effectiveness of anions was Cl- greater than Br- greater than I- approximately NO3-. Sulfate and acetate were ineffective. The optimal pH was 8.0. The activity of the purified enzyme was stimulated by the addition of lipid to the assay mixture. This enzyme hydrolyzed all 5'-nucleotides tested, but did not hydrolyze 3'-nucleotides or ribose 5-phosphate. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the enzyme appeared to be a single polypeptide, with a molecular weight of 72 kDa.
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PMID:Purification and characterization of membrane-bound 5'-nucleotidase of Vibrio parahaemolyticus. 254 26

The gene encoding the membrane-bound 5'-nucleotidase of Vibrio parahaemolyticus was cloned and expressed in Escherichia coli. Cells of E. coli harboring a plasmid, pNUT5, which carries the 5'-nucleotidase gene were able to grow on ATP as the sole source of carbon, although the original cells were not. The 5'-nucleotidase activity was detected in whole cells of E. coli harboring pNUT5 and in membrane vesicles prepared from these cells. Most properties of the 5'-nucleotidase produced in E. coli, that is, its requirements for Cl- and Mg2+, substrate specificity, and inhibition by Zn2+, were similar to those observed in V. parahaemolyticus, but some alterations in properties were observed: The 5'-nucleotidase was partially inducible in V. parahaemolyticus, but its expression in E. coli was completely constitutive. The specific activity of the 5'-nucleotidase in membrane vesicles of E. coli harboring the plasmid was 30 times that observed in whole cells, whereas the specific activities in membrane vesicles and in whole cells of V. parahaemolyticus were almost the same. A new, dense band of protein with an apparent molecular mass of 63 kDa was detected when membrane proteins of E. coli harboring the plasmid were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
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PMID:Cloning and expression of the 5'-nucleotidase gene of Vibrio parahaemolyticus in Escherichia coli and overproduction of the enzyme. 254 29

In rat liver mitochondria there exists an AMP-dephosphorylating activity which converts external 5'-AMP to adenosine. It exhibits a pH optimum of 7.5 and a Km(AMP) of 0.085 mM. Furthermore, this activity is stimulated by magnesium (Km = 0.5 mM) and seems to be not affected by low concentrations of ATP or ADP. From the characteristics of the enzyme the existence of a 5'-nucleotidase in rat liver mitochondria which is localized on the outer surface of the inner mitochondrial membrane was concluded. The enzyme may be important for the production of cellular adenosine.
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PMID:Identification and characteristics of a novel mitochondrial 5'-nucleotidase in rat liver. 254 10

Biologically active concentrations of potently vasoactive and platelet-active adenine nucleotides are generated in plasma by a variety of pathophysiological mechanisms. Although there is evidence that ATP and ADP are inactivated by endothelial ectonucleotidases, there has been little attempt to study the metabolic routes of their catabolism in blood or to assess the contribution of this process to their clearance in vivo. Therefore, we have studied the rates and patterns of catabolism of ATP, ADP, and AMP in whole blood, plasma, and isolated blood cells. Rates of degradation of each nucleotide in cell-free plasma ranged from 0.07-0.32 nmol/min/ml with 1 microM substrates to 1.1-3.6 nmol/min/ml with 100 microM substrates. The pattern of catabolism indicated that sequential dephosphorylation from ATP----ADP----AMP----adenosine occurs. In whole blood, the pattern was similar although ATP and ADP (but not AMP) breakdown was more rapid. This was due to leukocyte ectonucleotidase activity. The use of selective inhibitors demonstrated that catabolism was not due to nonspecific phosphatase activity and that plasma 5'-nucleotidase is distinct from ATPase or ADPase. In leukocytes, ATPase and ADPase activities were distinguishable, and each contributed substantially to the rates of catabolism in whole blood. Leukocyte 5'-nucleotidase did not measurably contribute to AMP dephosphorylation in blood. By comparison, ecto-ATPase and ecto-ADPase activities on cultured human umbilical vein endothelial cells were similar to those on leukocytes while endothelial 5'-nucleotidase per 10(6) cells was equivalent to the soluble activity in 1 ml of blood or plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolism of adenine nucleotides in human blood. 254 57

A rapid deenergization procedure was used to probe the regulation of in situ adenylate deaminase and 5'-nucleotidase in isolated adult rat heart cells. In cells depleted of ATP, the rate of ionosine monophosphate (IMP) production was fourfold greater in cells that had been respiring prior to deenergization than in cells that had been maintaining ATP stores through anaerobic glycolysis. This effect of respiratory inhibition was fully reversed by reaeration. When phenylephrine was present during preincubation, IMP production during a subsequent 5-minute rapid deenergization was increased by 70% in respiring cells and by 88% in those that had not been respiring. These effects of phenylephrine were abolished by prazosin. Adenosine production by cells without ATP was inversely related to that of IMP, whereas it was positively correlated with the amount of AMP remaining in cells after 5 minutes. We conclude from these data that rat heart adenylate deaminase is regulated by a product(s) of anaerobic glycolysis and by alpha 1-adrenergic stimulation. The production of intracellular adenosine in cells without ATP, on the other hand, is governed primarily by the concentration of AMP and appears to be catalyzed by the cytosolic type I 5'-nucleotidase.
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PMID:IMP production by ATP-depleted adult rat heart cells. Effects of glycolysis and alpha 1-adrenergic stimulation. 254 64

2',3'-Dideoxyinosine (ddlno) is a potent and selective inhibitor of human immunodeficiency virus in human lymphoid cells and monocytes/macrophages. Earlier studies [J. Biol. Chem. 263:15354 (1988)] showed that anabolism of ddlno in human lymphoid cells is mediated via an initial step of phosphorylation and subsequent amination to dideoxy-AMP via adenylosuccinate synthetase/lyase. Evidence was obtained that neither adenosine kinase nor deoxycytidine kinase is involved in the phosphorylation of this compound in human lymphoid cells. We now find that, in the presence of MgCl2, KCl, and inosine-5'-monophosphate as phosphate donor, purified cytosolic 5'-nucleotidase catalyzed the phosphorylation of ddlno. Although not phosphate donors, ATP, diadenosine tetraphosphate, and glycerate-2,3-bisphosphate stimulate this phosphorylation by the nucleotidase 4-5-fold. In addition to ddlno, the antiviral nucleoside analogs 2',3'-dideoxyguanosine and carbovir were substrates for this enzyme. The relative phosphorylation of these compounds varied with the concentration of the phosphate donor IMP. Approximate Km values of the nucleotidase for inosine, ddlno, dideoxyguanosine, and carbovir were, respectively, 3.4, 0.5, 0.9, and 1.7 mM. Although the substrate activity of dideoxynucleosides is inefficient, it appears likely that this nucleotidase is responsible for the metabolism of these compounds to their active nucleotides, yielding antiviral activity in human lymphoid cells.
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PMID:Phosphorylation of 2',3'-dideoxyinosine by cytosolic 5'-nucleotidase of human lymphoid cells. 254 85


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