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)

There has been increasing interest in the value of using soybean to delay or reduce the tumor incidence. This study was undertaken to investigate the possible protective effects of soybean against hepatocarcinogenesis induced by DL-ethionine. Accordingly, we measured biochemical changes occurring in serum and liver of rats treated with DL-ethionine in the presence or absence of soybean. Male albino rats were fed a control diet containing the hepatocarcinogen, DL-ethionine, or the control diet plus soybean 30%, or the control diet plus soybean plus DL-ethionine 0.25% for three months and then returned to a control diet for up to nine months. Rats fed a control diet plus DL-ethionine showed a gradual decrease in liver DNA, RNA, total protein, and liver weight and enzyme activities of liver transaminases (GOT and GPT) and alkaline phosphatase over the 7-month study period. This was followed by a large increase in the liver parameters at the end of the 9(th) month, except for 5'-nucleotidase and glucose-6-phosphatase that showed a large decrease. On the other hand, a gradual increase in the serum enzyme activities of GOT, GPT, 5-nucleotidase, alkaline phosphatase, and in the albumin/globulin (A/G) ratio is observed in the group of rats fed a control diet plus DL-ethionine compared to the control group over 8 months, and this was followed by a large increase in all serum parameters studied at nine-months. The administration of 30% soybean to the rat diet in addition to DL-ethionine maintained all parameters studied at near control values until the end of the 9(th) month. This study suggests that soybean has a protective effect against the hepatocarcinogenesis induced by DL-ethionine.
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PMID:Protective effect of soybean against hepatocarcinogenesis induced by DL-ethionine. 1546 21

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

The leukemia and lymphoma disease locus Evi12 was mapped to the noncoding region of a novel gene, Gnn (named for Grp94 neighboring nucleotidase), that is located immediately upstream of the Grp94/Tra1 gene on mouse chromosome 10. The Gnn gene is conserved in mice and humans. Expression of fusion constructs between GFP and Gnn cDNA isoforms in HEK-293 cells showed that Gnn proteins are located mainly in the cytoplasm. Immunoblotting experiments demonstrated the presence of multiple Gnn protein isoforms in most organs, with the lowest levels of expression of the protein detected in bone marrow and spleen. The Evi12-containing leukemia cell line NFS107 showed high levels of expression of a approximately 150-kDa Gnn isoform (Gnn107) that was not observed in control cell lines. Overexpression may be due to the viral insertion in Evi12. The Gnn107 protein is probably encoded by a Gnn cDNA isoform that is expressed exclusively in NFS107 cells and that includes sequences of TU12B1-TY, a putative protein with homology to 5'-nucleotidase enzymes. Interestingly, using Affymetrix gene expression data of a cohort of 285 patients with acute myeloid leukemia (AML), we found that GNN/TU12B1-TY expression was specifically increased in two AML clusters. One cluster consisted of all AML patients with a t(8;21) translocation, and the second cluster consisted of AML patients with a normal karyotype carrying a FLT3 internal tandem duplication. These findings suggest that we identified a novel proto-oncogene that may be causally linked to certain types of human leukemia.
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PMID:The common viral insertion site Evi12 is located in the 5'-noncoding region of Gnn, a novel gene with enhanced expression in two subclasses of human acute myeloid leukemia. 1582 39

In skeletal muscle, adenosine monophosphate (AMP) is mainly deaminated by AMP deaminase. However, the C34T mutation in the AMPD1 gene severely reduces AMP deaminase activity. Alternatively, intracellular AMP is dephosphorylated to adenosine via cytosolic AMP 5'-nucleotidase (cN-I). In individuals with a homozygous C34T mutation, cN-I might be a more important pathway for AMP removal. We determined activities of AMP deaminase, cN-I, total cytosolic 5'-nucleotidase (total cN), ecto-5'-nucleotidase (ectoN) and whole homogenate 5'-nucleotidase activity in skeletal muscle biopsies from patients with different AMPD1 genotypes [homozygotes for C34T mutation (TT); heterozygotes for C34T mutation (CT); and homozygotes for wild type (CC): diseased controls CC; and normal controls CC]. AMP deaminase activity showed genotype-dependent differences. Total cN activity in normal controls accounted for 57+/-22% of whole homogenate 5'-nucleotidase activity and was not significantly different from the other groups. A weak inverse correlation was found between AMP deaminase and cN-I activities (r2=0.18, p<0.01). There were no significant differences between different groups in the activities of cN-I, whole homogenate 5'-nucleotidase and ectoN, or in cN-I expression on Western blots. No correlation for age, fibre type distribution and AMPD1 genotype was found for whole homogenate nucleotidase, total cN and cN-I using multiple linear regression analysis. There was no gender-specific difference in the activities of whole homogenate nucleotidase, total cN and cN-I. The results indicate no changes in the relative expression or catalytic behaviour of cN-I in AMP deaminase-deficient human skeletal muscle, but suggest that increased turnover of AMP by cN-I in working skeletal muscle is due to higher substrate availability of AMP.
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PMID:Ecto- and cytosolic 5'-nucleotidases in normal and AMP deaminase-deficient human skeletal muscle. 1649 64

Neurotransmission can be affected by exposure to heavy metals, such as mercury and lead. ATP is a signaling molecule that can be metabolized by a group of enzymes called ecto-nucleotidases. Here we investigated the effects of mercury chloride (HgCl(2)) and lead acetate (Pb(CH(3)COO)(2)) on NTPDase (nucleoside triphosphate diphosphohydrolase) and ecto-5'-nucleotidase activities in zebrafish brain membranes. In vitro exposure to HgCl(2) decreased ATP and ADP hydrolysis in an uncompetitive mechanism and AMP hydrolysis in a non-competitive manner. Pb(CH(3)COO)(2) inhibited ATP hydrolysis in an uncompetitive manner, but not ADP and AMP hydrolysis. In vivo exposure of zebrafish to HgCl(2) or Pb(CH(3)COO)(2) (20mug/L, during 24, 96h and 30 days) caused differential effects on nucleotide hydrolysis. HgCl(2), during 96h, inhibited the hydrolysis of ATP, ADP and AMP. After 30 days of exposure to HgCl(2), ATP hydrolysis returned to the control levels, ADP hydrolysis was strongly increased and AMP hydrolysis remained inhibited. Exposure to Pb(CH(3)COO)(2) during 96h caused a significant decrease only on ATP hydrolysis. After 30 days, Pb(CH(3)COO)(2) promoted the inhibition of ATP, ADP and AMP hydrolysis. Semi-quantitative RT-PCR analysis showed no changes in the expression of NTPDase1 and 5'-nucleotidase, following 30 days of exposure to both metals. This study demonstrated that Hg(2+) and Pb(2+) affect the ecto-nucleotidase activities, an important enzymatic pathway for the control of purinergic signaling.
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PMID:Exposure to Hg2+ and Pb2+ changes NTPDase and ecto-5'-nucleotidase activities in central nervous system of zebrafish (Danio rerio). 1693 Jul 98

ATP is an important excitatory neurotransmitter and adenosine acts as a neuromodulatory structure inhibiting neurotransmitters release in the central nervous system. Since the ecto-nucleotidase cascade that hydrolyzes ATP to adenosine is involved in the control of brain functions and previous studies realized in our laboratory have recently reported that acute administration of Arg decreases the NTPDase and 5'-nucleotidase activities of rat blood serum, in the present study we investigated the effect of arginine administration on NTPDase and 5'-nucleotidase activities by synaptosomes from hippocampus of rats. First, sixty-days-old rats were treated with a single or a triple intraperitoneal injection of arginine (0.8 g/Kg) or an equivalent volume of 0.9% saline solution (control) and were killed 1 h later. Second, rats received an intracerebroventricular injection of 1.5 mM arginine solution or saline (5 microL) and were killed 1 h later. We also tested the in vitro effect of arginine (0.1-1.5 mM) on nucleotide hydrolysis in synaptosomes from rat hippocampus. Results showed that intraperitoneal arginine administration did not alter nucleotide hydrolysis. On the other hand, arginine administered intracerebroventricularly reduced ATP (32%), ADP (30%) and AMP (21%) hydrolysis, respectively. In addition, arginine added to the incubation medium, provoked a decrease on ATP (19%), ADP (17%) and AMP (23%) hydrolysis, respectively. Furthermore, kinetic studies showed that the inhibitory effect of arginine was uncompetitive in relation to ATP, ADP and AMP. In conclusion, according to our results it seems reasonable to postulate that arginine alters the cascade involved in the extracellular degradation of ATP to adenosine.
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PMID:NTPDase and 5'-nucleotidase activities of synaptosomes from hippocampus of rats subjected to hyperargininemia. 1740 61

Nucleoside monophosphate phosphohydrolases comprise a family of enzymes dephosphorylating nucleotides both in intracellular and extracellular compartments. Members of this family exhibit different sequence, location, substrate specificity and regulation. Besides the ectosolic 5'-nucleotidase, several cytosolic and one mitochondrial enzymes have been described. Nevertheless, researchers refer any AMP-dephosphorylating activity to as 5'-nucleotidase, lacking a more accurate identification. Increase of AMP hydrolysing activity has been associated with neurological and developmental disorders. The identification of the specific enzyme involved in these pathologies would be fundamental for the comprehension of the linkage between the enzyme activity alteration and brain functions. We demonstrate that the described neurological symptoms are associated with increased ectosolic 5'-nucleotidase activity on the basis of radiochemical assays and immunoblotting analysis. Furthermore, present data evidence that the assay conditions normally applied for the determination of cytosolic 5'-nucleotidases activity in crude extracts are affected by the presence of solubilised ectosolic nucleotidase.
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PMID:Identification of the nucleotidase responsible for the AMP hydrolysing hyperactivity associated with neurological and developmental disorders. 1761 44

Among the myriad of enzymes present in animal venoms, nucleotidases and nucleases are poorly investigated. Herein, we studied such enzymes in 28 crude venoms of animals found in Brazil. Higher levels of ATPase, 5'-nucleotidase, ADPase, phosphodiesterase and DNase activities were observed in snake venoms belonging to Bothrops, Crotalus and Lachesis genera than to Micrurus genus. The venom of Bothrops brazili snake showed the highest nucleotidase and DNase activities, whereas that of Micrurus frontalis snake the highest alkaline phosphatase activity. On the other hand, the venoms of the snake Philodryas olfersii and the spider Loxosceles gaucho were devoid of most nucleotidase and DNase activities. Species that exhibited similar nucleotidase activities by colorimetric assays showed different banding pattern by zymography, suggesting the occurrence of structural differences among them. Hydrolysis of nucleotides showed that 1 mol of ATP is cleaved in 1 mol of pyrophosphate and 1 mol of orthophosphate, whereas 1 mol of ADP is cleaved exclusively in 2 mol of orthophosphates. Pyrophosphate is barely hydrolyzed by snake venoms. Phosphodiesterase activity was better correlated with 5'-nucleotidase, ADPase and ATPase activities than with DNase activity, evidencing that phosphodiesterases are not the main agent of DNA hydrolysis in animal venoms. The omnipresence of nucleotidase and DNase activities in viperid venoms implies a role for them within the repertoire of enzymes involved in immobilization and death of preys.
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PMID:Nucleotidase and DNase activities in Brazilian snake venoms. 1790 25

HD-domain phosphohydrolases have nucleotidase and phosphodiesterase activities and play important roles in the metabolism of nucleotides and in signaling. We present three 2.1-A-resolution crystal structures (one in the free state and two complexed with natural substrates) of an HD-domain phosphohydrolase, the Escherichia coli 5'-nucleotidase YfbR. The free-state structure of YfbR contains a large cavity accommodating the metal-coordinating HD motif (H33, H68, D69, and D137) and other conserved residues (R18, E72, and D77). Alanine scanning mutagenesis confirms that these residues are important for activity. Two structures of the catalytically inactive mutant E72A complexed with Co(2+) and either thymidine-5'-monophosphate or 2'-deoxyriboadenosine-5'-monophosphate disclose the novel binding mode of deoxyribonucleotides in the active site. Residue R18 stabilizes the phosphate on the Co(2+), and residue D77 forms a strong hydrogen bond critical for binding the ribose. The indole side chain of W19 is located close to the 2'-carbon atom of the deoxyribose moiety and is proposed to act as the selectivity switch for deoxyribonucleotide, which is supported by comparison to YfdR, another 5'-nucleotidase in E. coli. The nucleotide bases of both deoxyriboadenosine-5'-monophosphate and thymidine-5'-monophosphate make no specific hydrogen bonds with the protein, explaining the lack of nucleotide base selectivity. The YfbR E72A substrate complex structures also suggest a plausible single-step nucleophilic substitution mechanism. This is the first proposed molecular mechanism for an HD-domain phosphohydrolase based directly on substrate-bound crystal structures.
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PMID:Structural insight into the mechanism of substrate specificity and catalytic activity of an HD-domain phosphohydrolase: the 5'-deoxyribonucleotidase YfbR from Escherichia coli. 1835 68

Limited prior evidence suggests that 5'-nucleotidase, an ectoenzyme principally located in the Malpighian tubules of the tick Rhipicephalus (Boophilus) microplus, could be an effective antigen in an anti-tick vaccine. To assess this, recombinant 5'-nucleotidase was expressed in Escherichia coli and used in vaccination trials with both sheep and cattle. Vaccinated sheep were challenged with freshly moulted adult ticks. Those with high titres of anti-nucleotidase antibodies showed significant protection against tick infestation, although protection was less than that found with the previously characterized antigen, Bm86. Cattle were vaccinated, in separate groups, with 5'-nucleotidase, Bm86 and both antigens combined. Cattle, as the natural host, were challenged with larval ticks. Although Bm86 showed typical efficacy, no significant protection was seen in cattle vaccinated with 5'-nucleotidase. Cattle receiving a dual antigen formulation were no better protected than those receiving Bm86 alone. One possible reason for the difference between host species, namely antibody titre, was examined and shown to be an unlikely explanation. This demonstrates a limitation of using a model host like sheep in vaccine studies.
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PMID:Experimental vaccination of sheep and cattle against tick infestation using recombinant 5'-nucleotidase. 2007 Aug 27


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