The role of de novo purine synthesis in lymphocyte transformation.
Genetic defects in purine metabolism are associated with severe immunodeficiency. Adenosine deaminase deficiency impairs the function of both B- and T-lymphocytes whereas in purine nucleoside (inosine) phosphorylase deficiency there is more severe impairment of T-lymphocyte functions than of B-lymphocyte functions. The relative unimportance of the salvage pathway catalysed by hypoxanthine-guanine phosphoribosyltransferase is shown by the normal responses of T-lymphocytes from patients with the Lesch-Nyhan syndrome to antigenic and mitogenic stimulation. A mild deficiency of B-lymphocyte function is found in these patients. Agents inhibiting the de novo pathway of purine synthesis, including azaserine, 6-mercaptopurine and azathioprine in low doses, block the responses of normal human lymphocytes to mitogenic stimulation. These observations emphasize the importance of the de novo pathway of purine synthesis in lymphocyte responses to antigenic and mitogenic stimulation. There is considerable heterogeneity in the amount of labelled uridine incorporated into human and rat lymphocytes. This does not appear to reflect only a difference between T- and B-lymphocytes
D000228:Adenine Phosphoribosyltransferase / Q000378:metabolism; D000243:Adenosine Deaminase / Q000172:deficiency; D000293:Adolescent; D000328:Adult; D000493:Allopurinol / Q000627:therapeutic use; D001377:Azaserine / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency; D007136:Immunoglobulins / Q000378:metabolism; D037102:Lectins / Q000494:pharmacology; D007926:Lesch-Nyhan Syndrome / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D015122:Mercaptopurine / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency; D011687:Purines / Q000096:biosynthesis*; D012313:RNA / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology; D013936:Thymidine / Q000378:metabolism; D014529:Uridine / Q000378:metabolism
D007136:Immunoglobulins; D037102:Lectins; D008934:Mitogens; D011687:Purines; D012313:RNA; D000493:Allopurinol; D010754:Phosphoribosyl Pyrophosphate; D001377:Azaserine; D015122:Mercaptopurine; D011683:Purine-Nucleoside Phosphorylase; D000228:Adenine Phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase; D000243:Adenosine Deaminase; D013936:Thymidine; D014529:Uridine