Human Lymphoblast Adenosine Deaminase

  • 155 Tris
  • Published 2002


Adenosine deaminase (adenosine aminohydrolase, ADA, EC is a purme catabohc enzyme which catalyzes the irreversible hydrolytic deammation of adenosine to produce mosine and equally as well catalyzes the conversion of deoxyadenosine to deoxymosine (1). Whale ADA activaty is widely distributed in human ussues, ats acuvity as notably highest in lymphoid tissues, such as thymus, spleen, lymph nodes as well as circulating peripheral blood lymphocytes (2-6). A geneuc deficaency of ADA has been causally associated with an autosomal recessive form of severe combined immunodeficaency disease, resulting in profound T cell dysfunction and variable, but usually mild, B cell immunosuppression (7). In an attempt to define the molecular mechamsms m ADA deficaency disease, studies in v t t ro have revealed that the maturation of precursor T lymphocytes is inhibited by an ADA mhibator while immature B lymphocytes are unaffected (8, 9). Also, the combination of deoxyadenosme and an ADA inhabator leads to the selective accumulation of dATP and cytotox~city xn cultured T lymphoblasts but not m B lymphoblasts (10), thereby mamxckmg the ADA deficaency disease. A high level of deoxynucleoude degrading enzyme(s) m B lymphoblasts appears to protect these cells from accumulating toxic levels of dATP (11-13). An associated, but less well understood, observation is that T cells or thexr precursors appear to be highly dependent on ADA activity for protectxon against deoxyadenosme tox~caty and for normal cell maturation. Indeed, several studies have shown the level of ADA activaty to be markedly elevated specifically m these T cells For example, ADA actwlty ~s 3to 10-fold elevated m normal thymocytes as compared to ammature B lymphocytes (4-6, 14, 15) and ts 2to 10-fold higher m T lymphoblasts cultured from patients wRh acute lymphoblastac leukemxa than m cultured B lymphoblasts (5, 14, 16-21). Possible causes for the elevated levels of ADA activity m T lymphoblasts

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@inproceedings{Tris2002HumanLA, title={Human Lymphoblast Adenosine Deaminase}, author={155 Tris}, year={2002} }