Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.17 (adenosine deaminase)
 5,206 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in levels of purine degradative enzymes have been shown to occur during T-cell maturation in both rats and humans with a fall in adenosine deaminase (ADA) and a rise in purine nucleoside phosphorylase (PNP) and 5'-nucleotidase (5'NT) activities. We have investigated the effects of four thymic factors: thymosin fraction 5 (TMS-F5); thymosin alpha 1 (TMS-alpha 1); thymopoietin pentapeptide (TP-5); and thymic conditioned medium (CM) on TdT activity, purine enzyme levels and the phenotypic markers OKT3 (a marker for mature T cells) and NA1/34 (which reacts with immature cortical thymocytes) in human thymocytes and in the lymphoid leukaemic cell lines RPMI-8402 and JM1 (derived from Thy-ALL). All four thymic factors caused one or more maturation change in human thymocytes, e.g. TMS-F5 caused a significant increase in OKT3 expression, TMS-alpha 1 a fall in TdT and ADA activities and a rise in OKT3-positive cells, TP-5 an increase in PNP and CM a rise in 5'NT activity. TMS-F5 also caused a marked elevation of 5'NT in both the T lymphoblastic lines (P less than 0.001). On the other hand the non-physiological phorbol ester, 12-O-tetradecanoyl phorbol acetate (TPA), a tumour promotor with potency of inducing differentiation in some leukaemic cell lines, induced changes in both normal thymocytes and in the leukaemic line JM1 were inconsistent with maturation, e.g. a fall in the percentage of OKT3 cells. These observations suggest that maturation of normal thymocytes might proceed stepwise, each step requiring at least one of the thymic hormones. Although thymosin also induces differentiation changes in a malignant lymphoid line, the pattern of these differs from that induced in their normal counterparts.
 ...
PMID:Biochemical and immunological differentiation of human thymocytes induced by thymic hormones. 660 5

High levels of adenosine deaminase (ADA) activity have been associated with normal T cell differentiation and T cell disease, such as acute lymphoblastic leukemia; however, possible mechanisms controlling the level of this enzyme have not been explored. In this study, the properties and rate of turnover of ADA are compared in cultured human T and B lymphoblast cell lines. (1) Relative to B lymphoblasts, the level of ADA activity in extracts of T lymphoblast cell lines (MOLT-4, RPMI-8402, CCRF-CEM and CCRF-HSB-2) is elevated 7- to 14-fold and differs by 2-fold among the T-cell lines. (2) In T and B lymphoblast extracts, the enzyme is apparently identical based on Km for adenosine and deoxyadenosine, Ki for inosine, Vmax for adenosine, S20w, isoelectric pH, and heat stability. Further, by radioimmunoassay the quantity of ADA immunoreactive protein is proportional to the level of enzyme activity in all cell lines studied. (3) Using a purification and selective immunoprecipitation technique, the enzyme turnover could be assessed in cell lines labeled with [35S]methionine. The apparent rate of ADA synthesis, relative to total protein, is 2-fold faster in both T cell lines (RPMI-8402 and CCRF-CEM) than in the B cell lines (MGL-8 and GM-130). The apparent half-life (t1/2) for the enzyme degradation is 19 and 39 hr, respectively, for CCRF-CEM and RPMI-8402, while the t1/2 for both B cell lines is 7-9 hr. From the net rate of synthesis and degradation, the T cell lines exhibit a 6- and 12-fold difference in ADA turnover relative to B cells, consistent with the observed differences in enzyme activity. (4) The level of ADA (activity and/or protein) in cultured T or B lymphoblasts is not influenced by either substrates or products of the ADA reaction or an ADA inhibitor or a selected group of immunosuppressive drugs added to these cells in culture. These studies indicate that while ADA is apparently identical in all T and B lymphoblasts, alterations in both the rate of ADA synthesis and degradation lead to its accumulation and high steady-state level in T cells.
 ...
PMID:Control of adenosine deaminase levels in human lymphoblasts. 698 Dec 87

Serum activity of the adenosine deaminase (ADA) isozyme, ADA2, has been reported to be elevated during various disease states. Macrophages have been suggested as the cellular source of extracellular ADA activity because they are one of the only cell types in which intracellular ADA2 activity has been measured, but extracellular secretion has never been demonstrated. Rat primary peritoneal macrophages (PPMs) and peripheral blood monocytes (PBMs) were harvested and incubated for 18 h in RPMI supplemented with horse serum. PPM and PBM lysates were assayed for intracellular ADA activity (ammonia production). In vitro and in vivo extracellular ADA activities were measured in media and rat serum, respectively. Activity of ADA1 was confirmed by selective inhibition with erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA). ADA2 activity was inhibited by 2'-deoxycoformcin only, and was increased at a low pH (6.5). Activity of both ADA isozymes was found in PPMs and PBMs, and their media. In a separate group of rats, peritonitis was induced by ip insertion of 400 mg/kg caecal slurry. PPMs were harvested 24 h later and incubated for 18 h. In PPMs from rats with peritonitis both isozymes were elevated by a similar proportion. In contrast, media from these PPMs had a lower ADA1 and a higher ADA2 activity compared to PPMs from nonseptic rats. This resulted in a greater proportion of ADA2 in media. The isozyme proportions in serum from septic rats more closely resembled that of the PPM media. The response of PBM was small relative to that of PPM. These results suggest that macrophages are a significant source of extracellular ADA isozymes, the activity of which increases during an inflammatory response. Because extracellular isozymes profiles differ from cellular concentrations, the data also suggest differential release of each isozyme from PPMs.
 ...
PMID:Macrophages are a source of extracellular adenosine deaminase-2 during inflammatory responses. 1537