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 disease is caused by a deficiency of the enzyme pyrimidine-5'-nucleotidase in the erythrocytes. About 50 cases have been published. We have diagnosed the disease in a pair of siblings from Numedal, Norway. Although this is a rare disorder it has a world-wide distribution. It is inherited as an autosomal recessive disease, and with genetic heterogeneity. In studies of iron balance we have found increased excretion of iron and hemoglobin in the urine, and free hemoglobin in plasma, indicating extravascular hemolysis. Kidney biopsy shows iron depositions in epithelial cells in proximal kidney tubules, localized to lysosomes. An evaluation by ordinary clinical examinations and laboratory tests do not indicate a progression of the disease over a ten-year period.
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PMID:[Pyrimidine-5'-nucleotidase deficiency--congenital hemolytic anemia with basophilic stippling of erythrocytes]. 1236 99

The effect of oxidative stress catalysed by transition metals appears to have a critical relevance for the structure and function not only of membrane lipids but also of integral membrane proteins in a complex lipid-protein assembling, and membrane-dependent function. The integral membrane enzyme 5'-nucleotidase is susceptible to Fe((2+))-ion catalysed oxidative modification, and the extent of enzyme inhibition is in inverse relationship (r = -0.820) with lipid peroxidation (MDA) level. This work is also a comparative study about possible effectiveness of different Fe-ion chelators (deferoxamine, Na-citrate, Na-salicylate, ammonium oxalate and EDTA), antioxidants (GSH, GSH/GSH-Px system, Cu, Zn-SOD and mannitol) and metal cations (Mg(2+) and Mn(2+)) to protect or restore Fe(2+)-ion induced 5'-nucleotidase inhibition and to suppress Fe(2+)-ion enhanced lipid peroxidation. Among the examined chelators it was only deferoxamine and Na-citrate that exerted a fully protective and reactivating ability; among the antioxidants it was only GSH; among the metal cations it was only Mn(2+). The ability to protect or restore 5'-nucleotidase activity and to diminish chain-induced lipid peroxidation is explicable in terms of: metal-binding ability, capacity of taking iron away from a biological molecule, or ability of transferring the damage to itself. After a short incubation period, the iron associated with enzyme or lipid hydroperoxides could be in a labile coordinative linkage, still able to interact with possible ligands or metal cations.
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PMID:Oxidative modification of rat liver 5'-nucleotidase: the mechanisms for protection and re-activation. 1193 67

This study determined whether a single 60-mg dose of ferrous sulfate interferes with fractional zinc absorption (FZA) at 7-9 wk of lactation. In a crossover design, 5 exclusively breast-feeding women were given either a single 60-mg iron supplement or no supplement. FZA was measured by analyzing zinc stable isotope tracers ((70)Zn and (67)Zn) in urine samples collected for 7 d after isotope dosing. A 0.7-micromol intravenous (IV) infusion of (70)Zn as ZnCl(2) in saline was followed by a 0.03-mmol oral dose of (67)Zn as ZnCl(2) given with a standardized meal. After a 7-d wash-out period, the supplement given was reversed and a second FZA measurement was taken. FZA was calculated from isotopic enrichments in urine measured by inductively coupled plasma mass spectrometry. Hemoglobin, plasma ferritin and transferrin receptor, and plasma 5'-nucleotidase, plasma zinc and erythrocyte zinc did not differ before the two measurements of zinc absorption. When women were given a single iron supplement, FZA was significantly lower, 21.7 +/- 1.7% compared with 26.9 +/- 2.6% when no supplement was given (P = 0.032). A single 60-mg iron dose significantly decreases FZA during early lactation.
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PMID:A single 60-mg iron dose decreases zinc absorption in lactating women. 1209 67

Cupric sulfate is an inorganic salt which is widely used in industry, agriculture, and veterinary medicine. Its applications include use as an algicide in potable waters and as a feed additive and therapeutic agent in swine, sheep, and cattle. Because copper salts are found in human water supplies, toxicity studies of cupric sulfate pentahydrate were conducted in male and female F344/N rats and B6C3F1 mice by the drinking water (2-week studies only) and dosed feed routes (2-week and 13-week studies). Animals were evaluated for hematology, clinical chemistry, urinalysis, reproductive toxicity, tissue metal accumulation, and histopathology. In the 2-week drinking water studies, groups of five rats and five mice per sex received cupric sulfate at concentrations of 300 to 30,000 ppm for 15 days. One female rat, one male mouse, and three female mice in the 3000 ppm groups and all rats and mice in the 10,000 and 30,000 ppm groups died before the end of the studies. The remaining mice and rats in the 3000 ppm groups gained little or lost weight. Water consumption in the three highest dose groups of both species was reduced by more than 65%. Clinical signs observed in these groups were typical of those seen in moribund animals and were attributed to dehydration. The only gross or microscopic change specifically related to cupric sulfate toxicity was an increase in the size and number of cytoplasmic protein droplets in the epithelium of the renal proximal convoluted tubule in male rats from the 300 and 1000-ppm groups. In the 2-week feed studies, groups of five rats and five mice per sex were fed diets containing 1000 to 16,000 ppm cupric sulfate. No chemical-related deaths occurred in any dose group. Compared to the controls, rats and mice in the two highest dose groups had reduced body weight gains which were attributed to decreased feed consumption. Hyperplasia with hyperkeratosis of the squamous epithelium on the limiting ridge of the forestomach was seen in rats and mice of each sex; this lesion was more severe in rats than in mice. Inflammation of the liver, periportal to midzonal in distribution, occurred in rats in the 8000 and 16,000 ppm groups. Depletion of hematopoietic cells was evident in rats of each sex in the bone marrow (8000 and 16,000 ppm) and spleen (16,000 ppm). Kidneys of male and female rats in the 4000, 8000, and 16,000 ppm groups had an increased number and size of protein droplets in the epithelia of the renal cortical tubules. In the 13-week feed studies, groups of 10 rats per sex received diets containing 500 to 8000 ppm cupric sulfate, and groups of 10 mice per sex received diets containing 1000 to 16,000 ppm cupric sulfate for 92 days; estimates of cupric sulfate consumption ranged from 32 to 551 mg/kg per day for rats and 173 to 4157 mg/kg per day for mice. There were no chemical-related deaths in rats or mice, and no clinical signs of cupric sulfate toxicity were recorded. Final mean body weights were lower than those of the controls for animals of both species receiving doses of 4000 ppm cupric sulfate and greater. In mice in the 13-week studies, there was a dose-related decrease in liver weights. Hematologic, clinical chemistry, and urinalysis evaluations of rats in the 13-week study revealed variable chemical-related changes that were, for the most part, restricted to the 4000 and 8000 ppm groups. Increases in serum alanine aminotransferase and sorbitol dehydrogenase activities in both sexes were indicative of hepatocellular damage, as were increases in 5'-nucleotidase and bile salts in males. Decreases in mean cell volume, hematocrit, and hemoglobin indicated the development of a microcytic anemia, while increases in reticulocyte numbers at the same time points suggested a compensatory response to the anemia by the bone marrow. Increases in urinary glucose and N-acetyl-beta-D-glucosaminidase (a lysosomal enzyme) and aspartate aminotransferase (alpha-cytosolic enzyme) were suggestive of renal tubule epithelial damage. Dose-related increases in copper occurred in all male rat tissues examined (lissues examined (liver, kidney, plasma, and testis). These increases were accompanied by increases in zinc in the liver and kidney. Plasma calcium was significantly reduced in the 4000 and 8000 ppm groups, and there was a trend toward reductions in calcium in the kidney and testis as well. In the 8000 ppm group, plasma magnesium was significantly increased relative to the controls. Rats in the three highest dose groups had hyperplasia and hyperkeratosis of the forestomach, inflammation of the liver, and increases in the number and size of protein droplets in the epithelial cytoplasm and the lumina of the proximal convoluted tubules. These effects were similar to those seen in the 2-week feed study, and the incidence and severity of these lesions were dose related. Many of the droplets in male rat kidneys were large and had irregular crystalline shapes. These droplets stained strongly positive for protein but were negative by iron, PAS, and acid-fast (lipofuscin) staining methods. α-2-Microglobulin was present in the droplets of male rats, but there was no dose- related, qualitative difference in the content of this protein. In the 4000 and 8000 ppm groups, copper was distributed in a periportal to midzonal pattern in the liver and was restricted to the cytoplasm of the proximal convoluted tubule epithelium in the kidney. Copper was present in some, but not all, of the protein droplets. Transmission electron microscopy of the livers of rats of each sex revealed increases in the number of secondary lysosomes in hepatocytes in the periportal area. In mice of each sex receiving 4000 ppm cupric sulfate and higher in the 13-week study, there was a dose-related increase in hyperplasia with hyperkeratosis of the squamous mucosa on the limiting ridge of the forestomach. Minimal positive staining for copper was present in the liver and was limited to high-dose (16,000 ppm) male and female mice. Cupric sulfate produced no adverse effects on any of the reproductive parameters measured in rats or mice of either sex. In summary, administration of cupric sulfate to rats in feed or drinking water resulted in significant gastric changes and hepatic and renal damage. The primary lesion in rats was an increase in the size and number of proteinaceous droplets in the epithelial cytoplasm and lumen of the proximal convoluted tubule. For rats in the 13-week study, the no-observed-adverse-effect level (NOAEL) for evidence of histologic injury to the kidney was 1000 ppm for males and 500 ppm for females, while the NOAEL for liver inflammation was 1000 ppm for males and 2000 ppm for females. Hyperplasia with hyperkeratosis of the epithelium on the limiting ridge separating the forestomach from the glandular stomach was also seen in rats of each sex, and the NOAEL for this change was 1000-ppm cupric sulfate in the feed. Additionally, clinical pathology alterations noted in the 13-week study, along with histologic changes in bone marrow noted in the 2-week feed study, were indicative of a microcytic anemia with a compensatory bone marrow response. Mice appeared to be much more resistant to the toxic effects of cupric sulfate than rats. The primary target tissue in mice was the epithelium of the limiting ridge of the forestomach. The NOAEL for the hyperplasia and hyperkeratosis seen at this site in mice was 2000-ppm cupric sulfate in the feed. Synonyms: Chalcanthite; Copper sulfate; cupric sulfate pentahydrate; bluestone; blue vitriol; Roman vitriol; Salzburg vitriol. (NOTE: These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.)
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PMID:NTP technical report on the toxicity studies of Cupric Sulfate (CAS No. 7758-99-8) Administered in Drinking Water and Feed to F344/N Rats and B6C3F1 Mice. 1220 95

Pyrimidine 5'-nucleotidase deficiency is a rare autosomal recessive disorder characterized by haemolytic anaemia, marked basophilic stippling and accumulation of pyrimidine nucleotides within the erythrocytes. The gene encoding for this enzyme (P5'N-1) has been cloned recently, and seven mutations have so far been identified in 11 unrelated families. We describe the haematological and molecular characteristics of six unrelated Italian patients affected by pyrimidine 5'-nucleotidase deficiency (one from northern and five from southern Italy). The sequence of the complete P5'N-1 gene showed the presence of four different new mutations: a missense mutation AAT-AGT at codon 190 (Asn-Ser), one splicing mutation (IVS9-1 g-c) and two frameshift mutations, DelG576 and InsGG743. Although the molecular defect was homozygous in all patients but one, parents' consanguinity could be confirmed in only one case. InsGG743 was detected in two cases, and DelG576 was found in three patients originating from southern Italy, suggesting a possible geographical distribution of the genetic defect. Haematological data showed the presence of peripheral spherocytosis in all cases, although only one had a concomitant membrane defect. An increase in serum ferritin levels was observed in the splenectomized patients, suggesting that the iron status of these subjects should be monitored and that they should be investigated for potential additional risk factors for iron accumulation.
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PMID:Molecular characterization of six unrelated Italian patients affected by pyrimidine 5'-nucleotidase deficiency. 1293 Mar 99

The activity of the enzymes NTPDase and 5'-nucleotidase was studied in both diabetes mellitus and an associated model of iron-overload. Rats were divided in five groups: citrate (CC), saline (S), diabetic (D), iron-overload (IO), and diabetic iron-overload (DIO). Diabetes was induced with alloxan (150 mg/kg), and iron-overload was induced with iron-dextran (10 intramuscular applications of +/-80 mg/kg). The enzymatic activities were evaluated in the platelets. The results demonstrated an increase in the activity of NTPDase with substrates ATP and ADP (60% and 120%, respectively; P<0.001), and 5'-nucleotidase (60%, P<0.001). This increase was more intense in the IO and DIO groups. The results obtained in vitro showed an activation in ATP, ADP, and AMP hydrolysis between 1 microM and 1,000 microM ferric nitrate concentrations, being more pronounced at 100 microM and decreasing at 1,000 microM. We concluded that diabetes mellitus in association with iron-overload increased the hydrolysis of adenine nucleotides in platelets, contributing to the abnormalities found in these pathological conditions.
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PMID:Enhanced NTPDase and 5'-nucleotidase activities in diabetes mellitus and iron-overload model. 1711 48

Conventional semen analysis has been used for prognosis and diagnosis of male fertility. Although this tool is essential for providing initial quantitative information about semen, it remains a subject of debate. Therefore, development of new methods for the prognosis and diagnosis of male fertility should be seriously considered for animal species of economic importance as well as for humans. In the present study, we applied a comprehensive proteomic approach to identify global protein biomarkers in boar spermatozoa in order to increase the precision of male fertility prognoses and diagnoses. We determined that l-amino acid oxidase, mitochondrial malate dehydrogenase 2, NAD (MDH2), cytosolic 5'-nucleotidase 1B, lysozyme-like protein 4, and calmodulin (CALM) were significantly and abundantly expressed in high-litter size spermatozoa. We also found that equatorin, spermadhesin AWN, triosephosphate isomerase (TPI), Ras-related protein Rab-2A (RAB2A), spermadhesin AQN-3, and NADH dehydrogenase [ubiquinone] iron-sulfur protein 2 (NDUFS2) were significantly and abundantly expressed in low-litter size spermatozoa (>3-fold). Moreover, RAB2A, TPI, and NDUFS2 were negatively correlated with litter size, whereas CALM and MDH2 were positively correlated. This study provides novel biomarkers for the prediction of male fertility. To the best of our knowledge, this is the first work that shows significantly increased litter size using male fertility biomarkers in a field trial. Moreover, these protein markers may provide new developmental tools for the selection of superior sires as well as for the prognosis and diagnosis of male fertility.
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PMID:Discovery of predictive biomarkers for litter size in boar spermatozoa. 2569 3

Studies demonstrated that the iron chelating antioxidant restores brain dysfunction induced by iron toxicity in animals. Earlier, we found that iron overload-induced cerebral cortex apoptosis correlated with oxidative stress could be protected by naringenin (NGEN). In this respect, the present study is focused on the mechanisms associated with the protective efficacy of NGEN, natural flavonoid compound abundant in the peels of citrus fruit, on iron induced impairment of the anxiogenic-like behaviour, purinergic and cholinergic dysfunctions with oxidative stress related disorders on mitochondrial function in the rat hippocampus. Results showed that administration of NGEN (50 mg/kg/day) by gavage significantly ameliorated anxiogenic-like behaviour impairment induced by the exposure to 50 mg of Fe-dextran/kg/day intraperitoneally for 28 days in rats, decreased iron-induced reactive oxygen species formation and restored the iron-induced decrease of the acetylcholinesterase expression level, mitochondrial membrane potential and mitochondrial complexes activities in the hippocampus of rats. Moreover, NGEN was able to restore the alteration on the activity and expression of ectonucleotidases such as adenosine triphosphate diphosphohydrolase and 5'-nucleotidase, enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. These results may contribute to a better understanding of the neuroprotective role of NGEN, emphasizing the influence of including this flavonoid in the diet for human health, possibly preventing brain injury associated with iron overload.
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PMID:Naringenin Mitigates Iron-Induced Anxiety-Like Behavioral Impairment, Mitochondrial Dysfunctions, Ectonucleotidases and Acetylcholinesterase Alteration Activities in Rat Hippocampus. 2605 Feb 8


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