Abstract
Cytosolic 5'-nucleotidase II (cN-II) is an intracellular 5'-nucleotidase characterized by substrate specificity. It preferentially hydrolyzes 6-hydroxypurine nucleotides such as IMP and GMP over AMP or UMP. cN-II is allosterically activated by ATP and inhibited by inorganic phosphate. It also has phosphotransferase activity and transfers phosphate moieties from IMP or GMP to nonphysiological nucleoside analogues used to treat some viral infections or malignancies. The cN-II gene has a strikingly conserved primary structure from humans to nematodes and its activity has been detected in various animals including snails. Its activity is highest in the livers of birds, crocodiles, lizards and snakes. The activity in chicken liver increases 2-fold by feeding a high-protein diet. These results suggest that cN-II participates, through IMP dephosphorylation, in production of uric acid as the main end product of aminonitrogen in these animals. Some studies suggest that cN-II participates in dephosphorylation of IMP accumulated in cells of some tissues to diffusible inosine for reutilization by other tissues. It has also been proposed that cN-II, together with purine nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase, constitutes the “oxypurine cycle”, thus regulating intracellular phosphoribosyl pyrophosphate (PRPP) concentrations. As for intracellular dephosphorylation of AMP, another intracellular 5'-nucleotidase, cN-I, is supposed to participate, because it hydrolyzes AMP more preferentially than IMP or GMP. However, for the tissues, in which the expression of cN-I is very low or undetectable, e.g. liver or brain tissues, results have been obtained that suggest the participation of cN-II in intracellular dephosphorylation of AMP.
Keywords: Allosteric regulation, cN-II, Energy charge, Enzymatic properties, Physiological roles, 5'-Nucleotidase, Phosphotransferase.
Current Medicinal Chemistry
Title:Enzymatic Properties and Physiological Roles of Cytosolic 5’-Nucleotidase II.
Volume: 20 Issue: 34
Author(s): Roichi Itoh
Affiliation:
Keywords: Allosteric regulation, cN-II, Energy charge, Enzymatic properties, Physiological roles, 5'-Nucleotidase, Phosphotransferase.
Abstract: Cytosolic 5'-nucleotidase II (cN-II) is an intracellular 5'-nucleotidase characterized by substrate specificity. It preferentially hydrolyzes 6-hydroxypurine nucleotides such as IMP and GMP over AMP or UMP. cN-II is allosterically activated by ATP and inhibited by inorganic phosphate. It also has phosphotransferase activity and transfers phosphate moieties from IMP or GMP to nonphysiological nucleoside analogues used to treat some viral infections or malignancies. The cN-II gene has a strikingly conserved primary structure from humans to nematodes and its activity has been detected in various animals including snails. Its activity is highest in the livers of birds, crocodiles, lizards and snakes. The activity in chicken liver increases 2-fold by feeding a high-protein diet. These results suggest that cN-II participates, through IMP dephosphorylation, in production of uric acid as the main end product of aminonitrogen in these animals. Some studies suggest that cN-II participates in dephosphorylation of IMP accumulated in cells of some tissues to diffusible inosine for reutilization by other tissues. It has also been proposed that cN-II, together with purine nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase, constitutes the “oxypurine cycle”, thus regulating intracellular phosphoribosyl pyrophosphate (PRPP) concentrations. As for intracellular dephosphorylation of AMP, another intracellular 5'-nucleotidase, cN-I, is supposed to participate, because it hydrolyzes AMP more preferentially than IMP or GMP. However, for the tissues, in which the expression of cN-I is very low or undetectable, e.g. liver or brain tissues, results have been obtained that suggest the participation of cN-II in intracellular dephosphorylation of AMP.
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Cite this article as:
Itoh Roichi, Enzymatic Properties and Physiological Roles of Cytosolic 5’-Nucleotidase II., Current Medicinal Chemistry 2013; 20 (34) . https://dx.doi.org/10.2174/0929867311320340006
DOI https://dx.doi.org/10.2174/0929867311320340006 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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