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

---

Query: EC:3.5.4.4 (adenosine deaminase)
5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A microassay requiring as few as 2 X 10(5) cells per assay was developed for systematic analysis of 9 purine enzymes in lymphocytes from equine peripheral blood, spleen, lymph node, thymus and bone marrow. The activities of adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), adenosine kinase (AK), deoxyadenosine kinase (dAK), deoxycytidine kinase (dCK), 5'-nucleotidase (5'-N), AMP deaminase, hypoxanthine-guanine phosphoribosyl transferase (HGPRT or HPRT), and adenine phosphoribosyl transferase (APRT) were measured by this microassay in lymphocytes from peripheral blood from four different breeds of horses (Arabian, Quarter Horse, Thoroughbred and Shetland Pony). There were no significant differences in the enzyme activities among the various breeds. Peripheral blood lymphocytes (PBL) from foals exhibited enzyme activities similar to those observed for adult animals. All lymphoid tissue contained similar levels of activity for each kinase (AK, dAK and dCK). Spleen had the highest activity for ADA, PNP, 5'-N, and HGPRT. The lowest activity for ADA, APRT, PNP and AMP deaminase was found in thymus. Enzymatic activities that varied the most among the tissue were 5'-N, ADA, APRT, HGPRT and AMP deaminase.
...
PMID:Distribution of enzymes of purine metabolism in lymphocytes of horse, Equus caballus. 299 Aug 11

A correlation between reactions of the sympathoadrenal system and the activity of adenosine transformation enzymes in lymphocytes is demonstrated in the dynamics of metastatic Lewis carcinoma development in C57Bl mice. In the period when metastases arise a decrease in the adenosine deaminase activity in lymphoid cells of the thymus and spleen is accompanied by drop in the content of DOPA, noradrenalin and adrenalin in adrenals. At the late stages of the tumour process a decrease in the amount of these compounds in adrenals is accompanied by the diminution of the adenosine deaminase activity and by an increase in the 5'-nucleotidase activity in the thymus. Contrary changes are observed in spleen lymphocytes. The revealed disturbances may stimulate to a considerable extent the appearance and growth of metastases.
...
PMID:[Enzymes of adenosine metabolism in lymphocytes and the functional state of the sympatho-adrenal system in tumor processes]. 301 May 22

Activities of key enzymes of purine metabolism [adenosine deaminase (AD); purine nucleoside phosphorylase (PNP); 5'-nucleotidase] were studied; changes in DNA content, nucleus ploidity in thymocytes, T- and B-lymphocytes in the C3HA mouse spleen during solid 22 hepatoma growth and after the immunization were monitored. Immunological properties of lymphocytes were also investigated measuring antibody formation and the reaction of blasttransformation in response to phytohemagglutinin, concanavalin A and lipopolysaccharide. Within the first 48 hrs after the tumor implantation and immunization certain nonspecific biochemical mechanisms of lymphocytes activation (elevated AD activity, decreased activity of 5'-nucleotidase, augmented intracellular DNA levels, polyploidity) were revealed. As the solid 22 hepatoma reached the maximum growth rate specific alterations in the activities of the purine metabolism key enzymes were observed reflecting the response of thymus and spleen lymphocytes to the presence of the malignant tumor.
...
PMID:[Biochemical and functional characteristics of thymus and spleen lymphocytes in C3HA mice during the growth of hepatoma 22 and after immunization with sheep erythrocytes]. 302 Jul 91

The promoter of the human gene for adenosine deaminase (ADA) is extremely G/C-rich, contains several G/C-box motifs (GGGCGGG) and lacks any apparent TATA or CAAT boxes. These features are commonly found in promoters of genes that lack a strong tissue specificity, and are referred to as "housekeeping genes". Like other housekeeping genes, the ADA gene is expressed in all tissues. However, there is a considerable variation in the levels of expression of the ADA protein in different tissues. In order to study the activity of the ADA promoter, transgenic mice were generated that harbor a chimeric gene composed of the ADA promoter linked to a reporter gene encoding the bacterial enzyme Chloramphenicol Acetyl Transferase (CAT). These mice reproducibly showed CAT expression in all tissues examined, including the hemopoietic organs (spleen, thymus and bone marrow). However, examination of the actual cell types expressing the CAT gene revealed the ADA promoter to be inactive in the hemopoietic cells. This was substantiated by a transplantation experiment in which bone marrow from ADA-CAT transgenic mice was used to reconstitute the hemopoietic compartment of lethally irradiated mice. The engrafted recipients revealed strongly reduced CAT activity in their hemopoietic organs. The lack of expression in hemopoietic cells was further shown to be correlated with a hypermethylated state of the transgene. Combined, our data suggest that the ADA promoter sequences tested can direct expression in a wide variety of tissues as expected for a regular housekeeping gene promoter. However, the activity of the ADA promoter fragment did not reflect the tissue-specific variations in expression levels of the endogenous ADA gene. Additionally, regulatory elements are needed for expression in the hemopoietic cells.
...
PMID:Activity of the adenosine deaminase promoter in transgenic mice. 305 38

In this study, we have investigated the distribution of adenosine deaminase (ADA) in embryonic, extra-embryonic, and decidual tissues of the developing mouse embryo. ADA catalyzes a key step in purine metabolism converting adenosine to inosine. ADA specific activity (nmol/min/micrograms protein) was present at low levels in the embryo-decidual unit during the first 2 days of postimplantation development but then increased starting late on Day 6 of gestation (Day 0 plug). By Day 9, ADA specific activity was 80-fold higher than on Day 6. A histochemical staining method for ADA activity was applied to cryostat sections of the implantation site. The developmental increase localized primarily to the trophoblast/antimesometrial decidua interface between Days 7 and 9 of gestation, and decidua basalis and the metrial gland by Day 11. Immunofluorescent staining with sheep anti-mouse ADA antiserum confirmed the presence of ADA antigenicity in tissues forming the maternal/fetal interface. ADA specific activity was 19-fold higher in homogenates of the Day 11 decidua/parietal yolk sac than in the thymus, a tissue generally thought of as ADA-rich. High levels of ADA activity and immunoreactivity were also detected in the embryonal plasma during organogenesis, but the embryo proper showed only low levels. These results indicate that ADA is tightly regulated within tissues forming the maternal/fetal interface during early postimplantation stages of development.
...
PMID:Developmental expression of adenosine deaminase in placental tissues of the early postimplantation mouse embryo and uterine stroma. 306 89

Pregnant mice were administered 2'-deoxycoformycin (2dCF), a potent inhibitor of adenosine deaminase activity, by intraperitoneal injection on day 7 or 15 of gestation or from day 8-12 or 14-18 of gestation. A total dose of 0.5 or 2.0 micrograms 2dCF/g of maternal body weight was given to the dams. In a separate study, pups born to nontreated dams were given 5 intraperitoneal injections totaling 0.5, 2.0 or 4.0 micrograms 2dCF/g beginning at 4 weeks of age. Administered doses of 2dCF were at levels known to profoundly suppress adenosine deaminase levels in adult mice. Pups born to dams injected with 2dCF from day 14-18 all died within 48 h of birth whereas other injection schedules had no effect on birth rate or survival of pups. In utero 2dCF exposure had little effect on immune function in offspring. On the other hand, body, spleen and thymus weight, and splenic cellularity were decreased in weanling mice 24 h after the last injection of 4 micrograms/g 2dCF. Proliferative responses of splenocytes to T cell mitogens and alloantigens were likewise suppressed at both 2.0 and 4.0 micrograms/g 2dCF. Suppression of proliferative responses in treated weanling mice were no longer apparent at 7 weeks of age although splenic cellularity and weight remained lower than control values. These results are similar to those we have reported for 8 week old mice given similar doses of 2dCF, with the exception of elevated levels of NK cell activity in older 2dCF-treated mice and suggest that there may be age-related differences in the sensitivity of certain cell populations to the effects of 2dCF.
...
PMID:Immune function in mice exposed to the adenosine deaminase inhibitor 2'-deoxycoformycin during immune system development. 350 94

Human thymus adenosine deaminase was isolated by using a monoclonal antibody affinity column. The highly purified enzyme produced by this rapid, efficient procedure had a molecular weight of 44,000. Quenching of the intrinsic protein fluorescence by small molecules was used to probe the accessibility of tryptophan residues in the enzyme and enzyme-inhibitor complexes. The fluorescence emission spectrum of human adenosine deaminase at 295-nm excitation had a maximum at about 335 nm and a quantum yield of 0.03. Addition of polar fluorescence quenchers, iodide and acrylamide, shifted the peak to the blue, and the hydrophobic quencher trichloroethanol shifted the peak to the red, indicating that the emission spectrum is heterogeneous. The fluorescence quenching parameters obtained for these quenchers reveal that the tryptophan environments in the protein are relatively hydrophobic. Binding of both ground-state and transition-state analogue inhibitors caused decreases in the fluorescence intensity of the enzyme, suggesting that one or more tryptophans may be near the active site. The kinetics of the fluorescence decrease were consistent with a slow conformational alteration in the transition-state inhibitor complexes. Fluorescence quenching experiments using polar and nonpolar quenchers were also carried out for the enzyme-inhibitor complexes. The quenching parameters for all enzyme-inhibitor complexes differed from those for the uncomplexed enzyme, suggesting that inhibitor binding causes changes in the conformation of adenosine deaminase. For comparison, parallel quenching studies were performed for calf adenosine deaminase in the absence and presence of inhibitors. While significant structural differences between adenosine deaminase from the two sources were evident, our data indicate that both enzymes undergo conformational changes on binding ground-state and transition-state inhibitors.
...
PMID:Immunoaffinity purification and fluorescence studies of human adenosine deaminase. 360 97

The activity of adenosine deaminase (ADA) was measured in 62 discrete regions of the CNS, and in some autonomic and sensory ganglia, peripheral nerves, and peripheral tissues of the rat using an automated high-pressure liquid chromatography (HPLC) method. The formation of inosine and hypoxanthine as a measure of ADA activity in homogenates of brain was optimal at pH 7.0, linear for up to 60 min at 37 degrees C using 500 microM adenosine as substrate, and linear with protein concentrations ranging from 0.05 to 0.8 mg. The Km and Vmax values for ADA activity in homogenates of whole brain were 47 microM and 107 nmol/mg protein/30 min, respectively. Among the CNS regions examined, the highest activity was found in posterior hypothalamic magnocellular nuclei and the lowest in hippocampus. In general, spinal cord contained relatively low levels of ADA activity, with that in dorsal cord approximately 40% higher than ventral cord. In the periphery, parasympathetic ganglia contained higher levels of ADA than sensory ganglia and brain. Most peripheral tissues--including adrenal gland, lung, liver, and anterior and posterior pituitary--exhibited activity comparable to levels in the posterior hypothalamus. ADA activity in thymus was about 10 times higher than any other tissue examined. The uneven distribution of ADA activity in the rat CNS corresponds well with the immunohistochemical localization of this enzyme in discrete neural systems of this species. Structures that contain high ADA activity exhibit intense ADA immunostaining of neuronal perikarya and/or fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Distribution of adenosine deaminase activity in rat brain and spinal cord. 374 29

The possibility that the mutant mouse wasted (wst/wst) may serve as an animal model for studies of severe combined immunodeficiency disease (SCID) and the role of adenosine deaminase (ADA, EC 3.5.4.4) in adenosine metabolism were investigated. The specific activity of ADA in wst/wst compared with control mice was significantly lower by 26% in thymus, but significantly higher by 18% in spleen and 32% in cerebellum. Vmax values of ADA in spleens were 43% higher in wst/wst mice and no changes were observed in Km values. In contrast, the Vmax of ADA was unchanged in erythrocytes from wst/wst mice, but the Km for adenosine was significantly elevated. Thus, based on ADA measurements alone, it may be premature to consider wst/wst mice as a model for ADA deficiency and SCID in humans.
...
PMID:Lack of adenosine deaminase deficiency in the mutant mouse wasted. 378 Sep 80

The dynamics of lymphocyte response in peripheral blood, the tumor draining lymph node, spleen and thymus, was followed in a model system of syngeneically transplanted rat MC-1 tumor. Electrophoretic mobility (EPM) of lymphoid cells was determined by the automatic mode of measurement. The results revealed a two-phase pattern of EPM changes during the course of cancer growth. The first phase (day 3 to 6 following intramuscular injection of tumor cells) was characterized by a prevalence of high-mobility cells, while in the second phase (day 14 to 20), depletion of high-mobility cells was compensated for by an increased number of low-mobility cells. The mean EPM value was found to be increased only in the thymus at that time. Changes in the adenosine deaminase activity proved to be most expressive in the tumor draining lymph node and in the second phase also in splenic and thymic lymphocytes. An increased percentage of active lymphocytes with compact nucleoli with nucleolonemas became evident already on the 3rd day in all the lymphoid organs followed. The response was two-phasic only in the lymphocyte population of the peripheral blood, while their percentage in the other organs remained higher even on day 20. Changes in the proportion of high- and low-mobility cells in the lymphoid organs followed here, in correlation with the adenosine deaminase activity and the percentage of active lymphocytes, were interpreted as a response of immunocompetent cells in animals with a growing tumor.
...
PMID:Kinetics of some immunological and biochemical changes of immunocompetent cells during tumor growth in rats. 378 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---