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)

Low activity of 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) in T lymphoblasts may explain the marked sensitivity of this cell to deoxynucleotide accumulation when compared to B lymphoblasts. The relevance of such observations with cultured cells to the normal immune system requires the demonstration of similar differences in the 5'-nucleotidase activity of normal human lymphocyte subpopulations. Sheep erythrocyte (E) rosette-forming cells from normal thymus, tonsil, and peripheral mononuclear cells have 5'-nucleotidase activities of 1.7, 11.3, and 21.2 nmol/hr per 10(6) cells. Non-E-rosette forming cells from the peripheral blood or tonsil have 5'-nucleotidase activity comparable to the higher levels found in the peripheral E-RFC. Increased levels of 5'-nucleotidase activity may be a marker for post-thymic T lymphocytes. T lymphoblasts have 5'-nucleotidase activity similar to values demonstrated for E-RFC in thymus, whereas cultured B lymphoblasts have 5'-nucleotidase activity 15 times greater than that of T lymphoblasts. On the basis of these observations, the 5'-nucleotidase deficiency in congenital agammaglobulinemia has been reevaluated. In these patients the data indicate that peripheral E-rosette forming cells have the enzyme deficiency, demonstrating an abnormality of T lymphocytes in this disorder of immunoglobulin production.
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PMID:Distribution of 5'-nucleotidase in human lymphoid tissues. 31 65

The activity of the lymphocyte ectoenzyme 5'-nucleotidase is very low in the majority of patients with primary 'common variable' hypogammaglobulinaemia. In order to test whether this can be explained by lymphocyte subpopulation deficiencies we measured 5'-nucleotidase activity, using both biochemical and histochemical techniques, in purified T and B cells from patients and healthy subjects. Purified B cells from normal subjects have about four times the activity of T cells. This explains why the levels of lymphocyte 5'-nucleotidase activity are at the lower limit of the normal range in patients with X-linked hypogammaglobulinaemia who lack B cells. The low levels in the 'common variable' group can be explained by low activity in their T lymphocytes associated with either low activity in their B cells or depletion of B cells. The finding that inhibition of the enzyme does not interfere with in vitro lymphocyte transformation or immunoglobulin production in normal subjects indicates that the enzyme deficiency is not directly responsible for the hypogammaglobulinaemia. These and other studies suggest that this enzyme appears on lymphocytes at a certain stage of development and that both T and B lymphocytes in some patients with 'common variable' hypogammaglobulinaemia are developmentally immature.
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PMID:Ecto 5'-nucleotidase deficiency in primary hypogammaglobulinaemia. 38 54

We report the case of a boy with severe combined immunodeficiency (SCID) and serious skin problems. The level of purine 5'-nucleotidase was greatly reduced in the lymphocytes of this patient. To our knowledge, no patients with SCID and this enzyme deficiency have been described previously. The relationship between reduced levels of this enzyme and the immunodeficiency is unclear. This case is also unusual because of the presence of large numbers of T lymphocytes expressing TCR1 (gamma/delta) in the skin. Moreover, the presence of so many TCR1-positive cells was not consistent with the low numbers of these cells in the peripheral blood. These cells were not present in skin biopsies taken at a later stage during the course of the disease. An oligoclonal lymphocytosis developed during follow-up, and a monoclonal antibody reactive with these clones was found, indicating that these lymphocytes were present in the skin. This case report illustrates the benefit of the use of monoclonal antibodies in identifying the cells involved in the cutaneous inflammation in SCID, in order to gain a better insight into the characteristics of these cells.
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PMID:The skin in severe combined immunodeficiency: a case with transient cutaneous presence of gamma/delta (TRC1+) T cells. 132 60

During the delivery of oxygen by erythrocytes, highly reactive oxygen species such as superoxide anion arise. The presence of reactive species damages the cell constituents. Glutathione (GSH) functions to repair cells when they are attacked by oxidative stress. GSH is synthesized in erythrocytes and glutathione disulfide (GSSG) is transported outside the cells to maintain a high GSH/GSSG ratio. The redox cycle of GSH by glutathione reductase and glutathione peroxidase is closely related to G6PD. Hereditary enzyme deficiency related to GSH metabolism, with hemolytic anemia has been reported. G6PD deficiency causes hemolytic anemia due to insufficiency of the redox cycle of GSH. Deficiency of GSH synthesizing enzymes or glutathione reductase also causes hemolysis. Pyrimidine 5'-nucleotidase deficiency causes hemolytic anemia even when there is a high concentration of GSH. Accumulation of nucleotides in red cells causes inhibition of G6PD activity.
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PMID:[Impaired glutathione metabolism in hemolytic anemia]. 219 89

Erythrocytes from patients with hereditary pyrimidine 5'-nucleotidase (P5N, EC 3.1.3.5) deficiency accumulate large quantities of several pyrimidine nucleotides and their derivatives. In addition, the reduced glutathione (GSH) concentration is elevated in erythrocytes from patients with this enzyme deficiency. In the present study, we were unable to demonstrate any effect of various pyrimidine nucleotides and their derivatives on enzymes of glutathione biosynthesis and metabolism. Thus, elevation of GSH levels in erythrocytes from P5N patients is not a result of modulation of these enzymes by pyrimidine nucleotides and their derivatives.
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PMID:Pyrimidine nucleotides do not affect the enzymes of glutathione biosynthesis. 286 97

With the use of a histochemical technique, 5'-nucleotidase activity was examined in peripheral blood lymphocytes from patients with primary hypogammaglobulinemia. Our current study demonstrates that the decrease in 5'-nucleotidase activity in congenital agammaglobulinemia, previously demonstrated by a radiochemical assay, is associated with a reduction in the number of cells containing 5'-nucleotidase rather than with a decrease of the enzyme activity per cell. Both sheep erythrocyte rosette-forming and nonrosette-forming PBMs have reduced percentages of 5'-nucleotidase-containing cells in subjects with the enzyme deficiency. The reduced percentage of 5'-nucleotidase-containing mononuclear cells in patients with congenital agammaglobulinemia was evident in both monocyte-contaminated and monocyte-depleted cell preparations.
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PMID:Histochemical evaluation of lymphocytes in hypogammaglobulinemia. Decreased number of 5'-nucleotidase-positive cells. 624 85

In this study 31 family members of a patient with erythrocyte pyrimidine 5'-nucleotidase deficiency were studied. The activity of this enzyme in their erythrocytes is compared with levels in normal subjects and the problems surrounding heterozygote detection are discussed. The mean erythrocyte pyrimidine 5'-nucleotidase activity in 158 normal fresh blood samples was 130 +/- SD 29.8 mU/gHb. There was no significant difference between males and females. The enzyme level in a patient with non-spherocytic haemolytic anaemia was 6 mU/gHb. Of 31 relatives of the enzyme deficient patient examined five were clearly heterozygous for the enzyme defect. Their enzyme levels were below 50 mU/gHb. The father, who is an obligatory heterozygote, had an enzyme level of 87 mU/gHb which falls within the low values of the normal range. The distribution of enzyme activity in 26 family members having enzyme activities greater than 50 mU/gHb suggests that six of these may be carriers of the defective gene. We were unable to identify carriers by enzyme kinetic studies, electrophoresis, chromatographic examination of acid extractable nucleotides or measurement of enzyme levels in young and old erythrocyte populations. The last-mentioned technique showed that erythrocyte 5'-nucleotidase activity in reticulocytes may be as high as 1785 mU/gHb and declines rapidly as the cell ages reaching about 50 mU/gHb in the oldest cells. Blood samples which had been stored frozen were examined to see whether such samples were satisfactory for population studies. The mean enzyme activity 151 blood samples stored frozen for more than 12 months was 153+/-SD 44.7 mU/gHb. The increase in enzyme levels in the frozen samples appears to be greatest in samples showing haemolysis. In spite of the increased enzyme level frozen samples could be used to detect subjects with enzyme deficiency and some heterozygotes.
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PMID:Erythrocyte pyrimidine 5'-nucleotidase. 625 42

Lymphocytes from three infants with reticuloendotheliosis and eosinophilia ( Omenn 's syndrome) and immunodeficiency were assayed for 5'-nucleotidase activity. B and T lymphocytes from all three patients were totally deficient in ecto-5'-nucleotidase activity, but had normal levels of cytoplasmic 5'-nucleotidase. In contrast, cultured lymphocytes expressed normal ectoplasmic and cytoplasmic activities, suggesting that the lymphocyte-restricted enzyme deficiency was not likely a primary genetic defect. The deficiency of lymphocyte ecto-5'-nucleotidase was not associated with any abnormality of deoxynucleoside metabolism. The absence of lymphocyte ecto-5'-nucleotidase may be a characteristic feature of this syndrome and may help to distinguish this disease from others with similar manifestations.
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PMID:Absence of lymphocyte ecto-5'-nucleotidase in infants with reticuloendotheliosis and eosinophilia (Omenn's syndrome). 632 96

Adenylosuccinase catalyses two reactions in purine metabolism: the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) into aminoimidazole carboxamide ribotide (AICAR) along the de novo synthesis of purine nucleotides, and the conversion of adenylosuccinate (S-AMP) into AMP in the conversion of IMP into AMP. The hallmarks of adenylosuccinase deficiency are the presence of succinylaminoimidazole carboxamide riboside (SAICAriboside) and succinyladenosine (S-Ado) in body fluids. These normally undetectable succinylpurines are the products of the dephosphorylation, by cytosolic 5'-nucleotidase, of the two substrates of adenylosuccinase. The clinical picture of the enzyme deficiency is markedly heterogeneous with, as a rule, a profound, but nevertheless variable degree of psychomotor delay, often convulsions and/or autistic features, sometimes growth retardation and muscular dystrophy. The diagnostic tests that can be used for diagnosis, the enzyme and gene defects that have been identified, and the hypotheses that have been put forward to explain the pathophysiology of the disorder are reviewed.
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PMID:Inborn errors of the purine nucleotide cycle: adenylosuccinase deficiency. 921 Nov 92

Pyrimidine-5'-nucleotidase type I (P5'NI) deficiency is an autosomal recessive condition that causes nonspherocytic hemolytic anemia, characterized by marked basophilic stippling and pyrimidine nucleotide accumulation in erythrocytes. We herein present two African descendant patients, father and daughter, with P5'N deficiency, both born from first cousins. Investigation of the promoter polymorphism of the uridine diphospho glucuronosyl transferase 1A (UGT1A) gene revealed that the father was homozygous for the allele (TA7) and the daughter heterozygous (TA6/TA7). P5'NI gene (NT5C3) gene sequencing revealed a further change in homozygosity at amino acid position 56 (p.R56G), located in a highly conserved region. Both patients developed gallstones; however the father, who had undergone surgery for the removal of stones, had extremely severe intrahepatic cholestasis and, liver biopsy revealed fibrosis and siderosis grade III, leading us to believe that the homozygosity of the UGT1A polymorphism was responsible for the more severe clinical features in the father. Moreover, our results show how the clinical expression of hemolytic anemia is influenced by epistatic factors and we describe a new mutation in the P5'N gene associated with enzyme deficiency, iron overload, and severe gallstone formation. To our knowledge, this is the first description of P5'N deficiency in South Americans.
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PMID:Pyrimidine-5'-nucleotidase Campinas, a new mutation (p.R56G) in the NT5C3 gene associated with pyrimidine-5'-nucleotidase type I deficiency and influence of Gilbert's Syndrome on clinical expression. 2515 5


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