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)

Escherichia coli contains a single periplasmic UDP-glucose hydrolase (5'-nucleotidase) encoded by ushA. Salmonella enterica, serotype Typhimurium, also contains a single UDP-glucose hydrolase but, in contrast to E. coli, it is membrane-bound and is encoded by the non-homologous ushB gene; Salmonella enterica (Typhimurium) also contains a silent allele of the ushA gene (ushA0). In this report, we show that nearly all natural isolates of Salmonella contain both UDP-sugar hydrolases, i.e. they are UshA+ UshB+. The only exceptions are all from sub-group I (S. gallinarum, S. pullorum, and most Typhimurium strains), are UshA- UshB+, and several have been shown to contain an ushA0 allele. These data, together with the fact that these latter strains are closely related genetically, strongly suggests a recent silencing mutation(s). We also report the presence in E. coli K-12, and in natural isolates of E. coli, of a DNA sequence which is homologous to the ushB gene of Salmonella; since E. coli does not contain UshB activity, we tentatively refer to this sequence as ushB0. Since all E. coli strains investigated are UshB-, we conclude that the silencing mutation(s) occurred relatively early following the divergence of Escherichia coli and Salmonella from a common ancestor that was ushA+ ushB+.
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PMID:UDP-sugar hydrolase isozymes in Salmonella enterica and Escherichia coli: silent alleles of ushA in related strains of group I Salmonella isolates, and of ushB in wild-type and K12 strains of E. coli, indicate recent and early silencing events, respectively. 828 6

P2 membrane receptors are specifically activated by extracellular nucleotides like ATP, ADP, UTP, and UDP. P2 receptors are subdivided into metabotropic P2Y and ionotropic P2X receptors. They are expressed in all tissues and induce a variety of biological effects. In epithelia, they are found in both the basolateral and the luminal membranes. Their widespread luminal expression in nearly all transporting epithelia and their effect on transport are summarized. The P2Y(2) receptor is a prominent luminal receptor in many epithelia. Other luminal P2 receptors include the P2X(7), P2Y(4), and P2Y(6) receptors. Functionally, luminal P2Y(2) receptor activation elicits differential effects on ion transport. In nearly all secretory epithelia, intracellular Ca(2+) concentration-activated ion conductances are stimulated by luminal nucleotides to induce Cl(-), K(+), or HCO(3)(-) secretion. This encompasses respiratory and various gastrointestinal epithelia or tissues like the conjunctiva of the eye and the epithelium of sweat glands. In the distal nephron, all active transport processes appear to be inhibited by luminal nucleotides. P2Y(2) receptors inhibit Ca(2+) and Na(+) absorption and K(+) secretion. Commonly, in all steroid-sensitive epithelia (lung, distal nephron, and distal colon), luminal ATP/UTP inhibits epithelial Na(+) channel-meditated Na(+) absorption. ATP is readily released from epithelial cells onto their luminal aspect, where ecto-nucleotidases promote their metabolism. Adenosine generated by the action of 5'-nucleotidase may elicit further effects on ion transport, often opposite those of ATP. ATP release from epithelia continues to be poorly understood. Integrated functional concepts for luminal P2 receptors are suggested: 1) luminal P2 receptors are part of an epithelial "secretory" defense mechanism; 2) they may be involved in the regulation of cell volume when transcellular solute transport is out of balance; 3) ATP and adenosine may be important autocrine/paracrine regulators mediating cellular protection and regeneration after ischemic cell damage; and 4) ATP and adenosine have been suggested to mediate renal cyst growth and enlargement in polycystic kidney disease.
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PMID:Control of epithelial transport via luminal P2 receptors. 1255 61

We have isolated and expressed a cDNA from the parasitic nematode Trichinella spiralis encoding a novel secreted nucleotidase which catalyses the hydrolysis of nucleoside 5'-diphosphates and 5'-monophosphates, but not 5'-triphosphates. The full length cDNA encodes a protein of 550 amino acids with an N-terminal signal peptide, but lacking a C-terminal signature sequence for addition of a glycosyl phosphatidylinositol (GPI) anchor. Expression in Pichia pastoris resulted in the secretion of an active enzyme with the catalytic properties of both a Mg2+-dependent diphosphohydrolase/apyrase and a 5'-nucleotidase. The protein sequence is homologous to 5'-nucleotidases from a wide variety of organisms but contains no sequences specifically conserved in apyrases, suggesting that it is a representative of a new class of secreted nucleotidase. The enzyme was essentially monospecific for AMP among the nucleoside 5'-monophosphates and catalysed the hydrolysis of nucleoside 5'-diphosphates in the order of UDP >> ADP. The diphosphatase activity was dependent on the presence of magnesium ions and a reducing agent, while the 5'-nucleotidase activity was enhanced by these additions. Kinetic analyses indicated that the enzyme exhibits allosteric behaviour. Determination of the number of active sites suggested that catalysis of the two different reactions occurs at the same active site. The data are discussed in terms of regulation of host purinergic signalling during infection.
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PMID:A nucleotidase with unique catalytic properties is secreted by Trichinella spiralis. 1547 4

AMP-activated protein kinase (AMPK) plays a key role in the regulation of energy homeostasis and is activated in response to cellular stress, including hypoxia/ischemia and hyperglycemia. The stress events are accompanied by rapid release of extracellular nucleotides from damaged tissues or activated endothelial cells (EC) and platelets. We demonstrate that extracellular nucleotides (ATP, ADP, and UTP, but not UDP) and adenosine independently induce phosphorylation and activation of AMPK in human umbilical vein EC (HUVEC) by the mechanism that is not linked to changes in AMP:ATP ratio. HUVEC express NTPDases, as well as 5'-nucleotidase; hence, nucleotides can be metabolized to adenosine. However, inhibition of 5'-nucleotidase had no effect on ATP/ADP/UTP-induced phospho- rylation of AMPK, indicating that AMPK activation occurred as a direct response to nucleotides. Nucleotide-evoked phosphorylation of AMPK in HUVEC was mediated by P2Y1, P2Y2, and/or P2Y4 receptors, whereas P2Y6, P2Y11, and P2X receptors were not involved. The nucleotide-induced phosphorylation of AMPK was affected by changes in the concentration of intracellular Ca2+ and by Ca2+/calmodulin-dependent kinase kinase (CaMKK), although most likely it was not dependent on LKB1 kinase. Adenosine-induced phosphorylation of AMPK was not mediated by P1 receptors but required adenosine uptake by equilibrative nucleoside transporters followed by its (intracellular) metabolism to AMP. Moreover, adenosine effect was Ca2+ and CaMKK independent, although probably associated with upstream LKB1. We hypothesize that P2 receptors and adenosine transporters could be novel targets for the pharmacological regulation of AMPK activity and its downstream effects on EC function.
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PMID:Extracellular nucleotides and adenosine independently activate AMP-activated protein kinase in endothelial cells: involvement of P2 receptors and adenosine transporters. 1649 86

In the respiratory system, extracellular nucleotides and nucleosides serve as signaling molecules for a wide spectrum of biological functions regulating airway defenses against infection and toxic material. Their concentrations are controlled by a complex network of cell surface enzymes named ectonucleotidases. This highly integrated metabolic network combines the activities of three dephosphorylating ectonucleotidases, namely nucleoside triphosphate diphosphohydrolases (NTPDases), nucleotide pyrophosphatase/phosphodiesterases (NPPs) and alkaline phosphatases (APs). Extracellular nucleotides are also inter-converted by the transphosphorylating activities of ecto adenylate kinase (ectoAK) and nucleoside diphosphokinase (NDPK). Different cell types use specific combinations of ectonucleotidases to regulate local concentrations of P2 receptor agonists (ATP, UTP, ADP and UDP). In addition, they provide AMP for the activity of ecto 5'-nucleotidase (ecto 5'-NT; CD73), which produces the P1 receptor agonist: adenosine (ADO). Finally, mechanisms are in place to prevent the accumulation of airway ADO, namely adenosine deaminases and nucleoside transporters. This chapter reviews the properties of each enzyme and transporter, and the current knowledge on their distribution and regulation in the airways.
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PMID:Mechanisms regulating airway nucleotides. 2156 43

Extracellular nucleotides are important triggers of innate immunity, acting on a wide variety of cells via signaling through purinergic receptors. Mucosal mast cells contribute to expulsion of a number of gastrointestinal nematode parasites, and mouse mast cell protease 1 has been shown to have a critical role in clearance of Trichinella spiralis from the intestinal tract. We show here that adenosine, ADP, ATP, UDP, and UTP all stimulate calcium mobilization in bone marrow-derived mast cells with a mucosal phenotype. Secreted proteins from T. spiralis infective larvae inhibit nucleotide-induced mast cell activation, and that induced by ADP and UDP is specifically blocked by parasite secretory 5'-nucleotidase. Release of mouse mast cell protease 1 is stimulated by ADP and ATP. Both parasite secreted products and the 5'-nucleotidase inhibit ADP-induced release of mast cell protease, whereas that stimulated by ATP is partially inhibited by secreted products alone. This indicates that the 5'-nucleotidase contributes to but is not solely responsible for inhibition of nucleotide-mediated effects on mast cell function. Secretion of nucleotide-metabolizing enzymes by parasitic nematodes most likely evolved as a strategy for suppression of innate immune responses and is discussed in this context.
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PMID:Trichinella spiralis secreted enzymes regulate nucleotide-induced mast cell activation and release of mouse mast cell protease 1. 2289 Sep 94


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