title: [Immune insufficiency in enzyme defects of purine metabolism].
abstract: Adenosine deaminase (EC 3.5.4.4. - ADA) deaminates adenosine and deoxyadenosine to inosine and deoxyinosine. The distribution of ADA isoenzymes depends on a binding protein. Purine nucleoside phosphorylase (EC 2.4.2.1. - PNP) catabolizes inosine and guanosine to hypoxanthine and guanine. Patients with severe combined immuno-insufficiency often suffer from a congenital ADA deficiency. The PNP deficiency is associated with severely defective T-cell immunity and normal B-cell immunity. Deficiency of ADA leads to an accumulation of adenosine, deoxyadenosine, adenine nucleotides (cAMP, dATP). In PNP deficiency an increased production of inosine, guanosine, deoxyinosine and deoxyguanosine was found. The pathogenesis of the immuno-insufficiency is to be traced back to disturbances in the purine metabolism interfering with the mitogenically induced lymphocyte transformation and other lymphocyte functions, as determined by in vitro tests. Deoxyadenine inhibits the ribonucleoside diphosphate reductase and synthesis of DNA. The overproduction of S-adenosyl-L-homocysteine inhibits methyltransferase reactions and 2'-deoxyadenosine the S-adenosylhomocysteine hydrolase. A decrease of ADA activities was found in T-lymphocytes of patients with Hodgkin's disease. Measurements of ADA activity in patients with leukemias do not explain the impairment of the cellular immune response in leukemias and may be regarded as indicator of increased purine metabolism. The ADA activities are increased in patients with acute immature and chronic myeloic leukemias depending on the activity of the disease. The ADA activity is low in chronic lymphatic leukemia. ADA inhibitors were used for the treatment of T-cell leukemias.
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency*; D000242:Cyclic AMP / Q000378:metabolism; D006689:Hodgkin Disease / Q000201:enzymology; D006801:Humans; D007111:Immunity, Cellular; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology*; D007527:Isoenzymes / Q000172:deficiency; D007938:Leukemia / Q000201:enzymology; D009700:Nucleoside Deaminases / Q000172:deficiency*; D010430:Pentosyltransferases / Q000172:deficiency*; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency*; D011687:Purines / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D011687:Purines; D000242:Cyclic AMP; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase
vernacular_title: Immuninsuffizienz durch Enzymdefekte des Purinstoffwechsels.