A role for purine metabolism in the immune response: Adenosine-deaminase activity and deoxyadenosine catabolism.
We have investigated a new hypothesis for the association between adenosine deaminase (A.D.A.) deficiency and immunodeficiency--namely, that deoxyadenosine rather than adenosine (an equally effective A.D.A. substrate) is toxic to proliferating cells of lymphoid origin. This possibility was explored in mitogen-stimulated lymphocytes cultured with a potent A.D.A. inhibitor, E.H.N.A. (erythro-9[2-hydroxy-3-nonyl] adenine) to simulate A.D.A. deficiency. In this in-vitro system deoxyadenosine was inhibitory at much lower and more physiological concentrations (1 mumol/1), compared with adenosine (100 mumol/1).
D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000172:deficiency* / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D002470:Cell Survival; D002478:Cells, Cultured; D002648:Child; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003839:Deoxyadenosines / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology*; D066298:In Vitro Techniques; D037102:Lectins / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008934:Mitogens / Q000494:pharmacology; D009700:Nucleoside Deaminases / Q000172:deficiency*; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000150:complications*
D058892:Adenosine Deaminase Inhibitors; D003839:Deoxyadenosines; D004791:Enzyme Inhibitors; D037102:Lectins; D008934:Mitogens; D003208:Concanavalin A; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D000241:Adenosine