The metabolism of deoxyguanosine and guanosine in human B and T lymphoblasts. A role for deoxyguanosine kinase activity in the selective T-cell defect associated with purine nucleoside phosphorylase deficiency.
Purine nucleoside phosphorylase (NP; EC 2.4.2.1) deficiency is associated with defective T-cell and normal B-cell immunity. Biochemical mechanisms were investigated by measuring deoxyguanosine and guanosine metabolism in normal T and B lymphoblasts and NP-deficient B lymphoblasts. Deoxyguanosine kinase activity was specifically measured by using an anti-NP antibody to prevent alternative-product formation. Kinase activity towards deoxyguanosine was significantly higher in T-cells, whereas NP activity was similar in both B- and T-cells. Only in T-cells was dGTP produced from exogenous deoxyguanosine, and this was prevented by the simultaneous addition of deoxycytidine, which resulted in a concomitant increase in GTP synthesis. Inhibition by 8-aminoguanosine of NP activity in T lymphoblasts increased formation of dGTP and decreased that of GTP from deoxyguanosine and decreased the formation of GTP from guanosine. These data suggest a central role for deoxyguanosine kinase activity in the T-cell selectivity of the immune defect.
D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D003841:Deoxycytidine / Q000494:pharmacology; D003849:Deoxyguanosine / Q000378:metabolism*; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D010430:Pentosyltransferases / Q000172:deficiency*; D010770:Phosphotransferases / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor); D011685:Purine Nucleotides / Q000378:metabolism; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D011685:Purine Nucleotides; D003841:Deoxycytidine; D006151:Guanosine; C032533:8-aminoguanosine; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C019165:deoxyguanosine kinase; D003849:Deoxyguanosine