Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphocytes from patients with primary immunodeficiency were tested histochemically for ecto 5'-nucleotidase (5'N) and alpha-naphthyl (non-specific) esterase. More than half the patients with 'common variable' hypogammaglobulinaemia, all those with X-linked hypogammaglobulinaemia and some of those with selective IgA deficiency had a very low percentage of lymphocytes staining for 5'N as compared to controls. A lack of B cells probably explains the finding in X-linked hypogammaglobulinaemia, but does not fully explain the results in the other groups. Most patients with 'common variable' hypogammaglobulinaemia had a very low percentage of lymphocytes with granular staining for alpha-naphthyl (non-specific) esterase in contrast to normal numbers in those with X-linked hypogammaglobulinaemia and most of those with selective IgA deficiency. Granules containing non-specific esterase are characteristically found in 'mature' T lymphocytes. The enzyme abnormalities in the T and B cells of 'common variable' hypogammaglobulinaemic patients could be explained by 'immature' cell types.
 ...
PMID:Histochemical studies for 5'-nucleotidase and alpha-naphthyl (non-specific) esterase in lymphocytes from patients with primary immunoglobulin deficiencies. 46 56

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.
 ...
PMID:The skin in severe combined immunodeficiency: a case with transient cutaneous presence of gamma/delta (TRC1+) T cells. 132 60

2',3'-Dideoxyguanosine (ddGuo) is a selective inhibitor of the replication of human immunodeficiency virus in vitro and the most active antihepadnavirus nucleoside analog known in vitro and in vivo, in a Peking duck model. However, the exact route by which this and related guanosine analogs are anabolized to their putative active metabolites in target cells is controversial. The anabolic pathway for the activation of ddGuo was investigated with the use of mutant human lymphoid CCRF-CEM and WI-L2 cell lines deficient in known nucleoside kinases. Uptake of ddGuo by human lymphoid cells and subsequent conversion to mono-, di-, and triphosphorylated metabolites is dose dependent and occurs proportionately to the exogenous concentration of drug. Studies with kinase-deficient CCRF-CEM and WI-L2 mutants revealed that at least two different routes of metabolism are operating in these cells to initiate the phosphorylation of ddGuo to its active dideoxynucleotides, one being deoxycytidine (dCyd) kinase and the other a cytosolic-5'-nucleotidase acting in the anabolic direction as a phosphotransferase. The evidence for this included 1) a lower but significant accumulation of drug anabolites in dCyd kinase-deficient mutants, 2) a lack of cross-resistance of the kinase-deficient mutants to growth inhibition by ddGuo, compared with that by the related analogs dideoxycytidine and arabinosylcytosine, known substrates for dCyd kinase, and 3) identification of different phosphorylation activities for ddGuo in extracts of wild-type cells and kinase-deficient mutants. Knowledge of the enzyme systems involved in anabolism of ddGuo analogs should be important for both new drug design and optimal therapeutic application.
 ...
PMID:Metabolic pathways for the activation of the antiviral agent 2',3'-dideoxyguanosine in human lymphoid cells. 132 48

Ribavirin enhances the anti-human immunodeficiency virus activity of 2',3'-dideoxyinosine (ddIno) in MT-4, CEM and peripheral blood lymphocyte cells. Ribavirin causes an increase in the levels of IMP, the presumed phosphate donor for the conversion of ddIno to ddIMP by 5'-nucleotidase. Consequently, ribavirin stimulates the conversion of ddIno to its antivirally active metabolite ddATP. Ribavirin also causes a marked depletion of the guanine nucleotide pools. The increase in IMP pool levels may result from (i) a direct inhibitory effect of ribavirin 5'-monophosphate on IMP dehydrogenase (which converts IMP to XMP) and (ii) an indirect inhibition of adenylosuccinate synthetase by the decreased GTP and dGTP pools (since GTP is an obligatory cofactor in the conversion of IMP to succinyl AMP). GTP depletion plays a key role in the accumulation of IMP and the resultant higher rate of ddIno phosphorylation to ddIMP and eventually ddATP. Our findings are in agreement with the observations that guanosine and 2'-deoxyguanosine, but not 2'-deoxyadenosine, reverse (i) the stimulatory effect of ribavirin on the anti-human immunodeficiency virus activity of ddIno and (ii) the accumulation of endogenous IMP pools as well as accumulation of [3H]IMP from exogenous [3H]hypoxanthine in ribavirin-treated cells.
 ...
PMID:Mechanism of the potentiating effect of ribavirin on the activity of 2',3'-dideoxyinosine against human immunodeficiency virus. 193 81

This review delineates the subcellular distribution, biochemical characteristics, and metabolic functions of 5'-nucleotidase (5'NT), summarizes the analytical biochemistry of 5'NT, and assesses the clinical significance of 5'NT determinations in body fluids, cells, and tissues. Salient aspects of the clinical biochemistry of 5'NT, discussed herein, are as follows: (A) Serum 5'NT activity is generally elevated in hepatobiliary diseases, especially with intrahepatic obstruction, but, unlike serum alkaline phosphatase, serum 5'NT activity is not increased in infancy, childhood, pregnancy, or osteoblastic disorders. (B) In cancer patients, elevated serum 5'NT activity does not always indicate hepatobiliary involvement; in some cases, 5'NT may be released into serum from the primary tumor or local metastases. (C) Genetic deficiency of erythrocyte pyrimidine 5'NT activity is a common cause of hereditary non-spherocytic hemolytic anemia. (D) Acquired deficiency of erythrocyte pyrimidine 5'NT activity occurs in patients with beta-thalassemia and lead poisoning. (E) 5'NT activity is low in circulating monocytes, increases markedly upon their differentiation to tissue macrophages, and subsequently diminishes during macrophage activation. (F) Lymphocyte ecto-5'NT activity, a plasma membrane marker of cell maturation, is generally low in immunodeficiency states, and undergoes characteristic changes in patients with certain lymphomas and leukemias.
 ...
PMID:The clinical biochemistry of 5'-nucleotidase. 218 4

Functional studies were performed on human peripheral blood T lymphocytes stained with goat anti-5'-nucleotidase antibodies and separated into ecto-5'-nucleotidase (ecto-5'-NT)-positive and -negative populations using the FACSTAR fluorescence-activated cell sorter. On the average, ecto-5'-NT+ T cells contained 34 +/- 13% CD4+ and 55 +/- 15% CD8+ cells, whereas ecto-5'-NT-T cells contained 65 +/- 12% CD4+ and 23 +/- 8% CD8+ cells. Staining with anti-5'-NT antibodies did not significantly alter the ability of unseparated T cells to proliferate in response to PHA or PMA, or in a MLR. However, prior incubation with anti-5'-NT antibodies did inhibit the ability of irradiated T cells to provide help for PWM-stimulated Ig synthesis by as much as 55%. In five separate experiments, ecto-5'-NT-T cells demonstrated an equal or better ability to incorporate [3H]TdR after PHA stimulation or in a MLR, as compared with ecto-5'-NT+ T cells. Similarly, ecto-5'-NT- T cells were not diminished in their ability to provide help for autologous B cells in a PWM-driven system. Clearly, the inability of ecto-5'-NT- T cells from patients with a variety of immunodeficiency diseases to function in these assays cannot be explained solely by their lack of ecto-5'-NT activity. In contrast, ecto-5'-NT-positive and -negative T cells showed markedly different dose-response curves for proliferation in response to PMA. Ecto-5'-NT+ T cells responded to lower doses of PMA (1.0 ng/ml) than did ecto-5'-NT- T cells and showed a two- to eight-fold greater rate of [3H]TdR incorporation at 3 to 10 ng of PMA per ml. Ecto-5'-NT+ T cells may have a protein kinase C that is more accessible or more easily activated or may utilize an alternate pathway of activation when stimulated with low concentrations of PMA.
 ...
PMID:Functional characterization of ecto-5'-nucleotidase-positive and -negative human T lymphocytes. 253 56

2',3'-Dideoxyinosine (ddlno) is a potent and selective inhibitor of human immunodeficiency virus in human lymphoid cells and monocytes/macrophages. Earlier studies [J. Biol. Chem. 263:15354 (1988)] showed that anabolism of ddlno in human lymphoid cells is mediated via an initial step of phosphorylation and subsequent amination to dideoxy-AMP via adenylosuccinate synthetase/lyase. Evidence was obtained that neither adenosine kinase nor deoxycytidine kinase is involved in the phosphorylation of this compound in human lymphoid cells. We now find that, in the presence of MgCl2, KCl, and inosine-5'-monophosphate as phosphate donor, purified cytosolic 5'-nucleotidase catalyzed the phosphorylation of ddlno. Although not phosphate donors, ATP, diadenosine tetraphosphate, and glycerate-2,3-bisphosphate stimulate this phosphorylation by the nucleotidase 4-5-fold. In addition to ddlno, the antiviral nucleoside analogs 2',3'-dideoxyguanosine and carbovir were substrates for this enzyme. The relative phosphorylation of these compounds varied with the concentration of the phosphate donor IMP. Approximate Km values of the nucleotidase for inosine, ddlno, dideoxyguanosine, and carbovir were, respectively, 3.4, 0.5, 0.9, and 1.7 mM. Although the substrate activity of dideoxynucleosides is inefficient, it appears likely that this nucleotidase is responsible for the metabolism of these compounds to their active nucleotides, yielding antiviral activity in human lymphoid cells.
 ...
PMID:Phosphorylation of 2',3'-dideoxyinosine by cytosolic 5'-nucleotidase of human lymphoid cells. 254 85

We herein report five new cases of severe combined immunodeficiency with hypereosinophilia, the so-called familial reticuloendotheliosis first described by Omenn. It is characterized by erythroderma, polyadenopathy, hepatosplenomegaly, severe and repeated infections, protracted diarrhoea with failure to thrive. There is marked eosinophilia as well as a profound immunodeficiency. The immunologic abnormalities consist of an increase in T cell number, a B cell lymphopenia and a complete lack of humoral and cellular immune responses to antigens. A deficiency of lymphocytes 5'-nucleotidase has been inconstantly found. Histologic findings are characteristic, consisting of severe T and B lymphocyte depletion in lymphoid organs with infiltration by histiocytes and, to a lesser extent, eosinophils. The outcome was uniformly fatal within the first year of life. Treatment by a combination of parenteral nutrition, steroids and epipodophyllotoxin was effective in obtaining the complete remission of clinical manifestations due to the histiocytic and eosinophilic infiltration in two patients. However, the treatment failed to correct the immunologic defect. These results indicate that the histiocytic infiltration is possibly not responsible for the immunologic detect observed in this condition.
 ...
PMID:[Severe combined immune deficiency with hypereosinophilia. Immunologic study of 5 cases]. 298 12

Immunologic surface markers, 5'-nucleotidase activity, and in vitro cell functions were determined on peripheral blood mononuclear cells from 20 patients with primary humoral immunodeficiencies. Imbalances of T-cell subsets were a frequent finding and often associated with a deficiency of helper T lymphocytes, predominantly in common variable immunodeficiency. The magnitude of the blastogenic response to mitogens was subnormal in the majority of the samples and showed no correlations to the proportions of helper, suppressor T cells or monocytes in the cultures. Moderate to marked suppression of the pokeweed mitogen-driven allogenic B-cell maturation was mostly mediated by T lymphocytes but modified by monocytes in some patients. In identical twins, T lymphocytes selectively suppressed IgA production. Both in sex-linked agammaglobulinemia and common variable immunodeficiency the activity of 5'-nucleotidase was significantly lower than in controls. This deficiency was mediated by T lymphocytes and showed no correlations to imbalances of T-cell subpopulations or to alterations of lymphocyte functions.
 ...
PMID:Surface markers, 5'-nucleotidase activity, and in vitro functions of lymphocytes from patients with primary humoral immunodeficiency. 298 85

The levels of three purine salvage enzymes, adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and 5'-nucleotidase (5'-N), which are known to be associated with certain immunodeficiency disorders were determined in mouse T lymphocytes. These enzymes showed characteristic changes depending on the stage of T cell development. The activity of ADA was 5-fold higher in thymocytes compared to splenic T cells. On the other hand, the splenic T cells displayed a 2-fold and a 4-8 fold greater activity of PNP and 5'-N, respectively than those of thymocytes. The apparent Km and Vmax values have been determined for all the 3 enzymes in the immature and mature T cells. The data demonstrate that the absolute and relative activity of these enzymes may be used as biochemical markers to characterize the T lymphocytes during different stages of differentiation.
 ...
PMID:Enzymes of nucleic acid metabolism as biochemical markers of T cell development in mouse. 608 53


1 2 Next >>