Biochemical basis for differential deoxyadenosine toxicity to T and B lymphoblasts: role for 5'-nucleotidase.
Deoxyadenosine metabolism was investigated in cultured human cells to elucidate the biochemical basis for the sensitivity of T lymphoblasts and the resistance of B lymphoblasts to deoxyadenosine toxicity. T lymphoblasts have a 20-to 45-fold greater capacity to synthesize deoxyadenosine nucleotides than B lymphoblasts at deoxyadenosine concentrations of 50--300 micron. During the synthesis of dATP, T lymphoblasts accumulate large quantities of dADP, whereas B lymphoblasts do not accumulate dADP. Enzymes affecting deoxyadenosine nucleotide synthesis were assayed in these cells. No substantial differences were evident in activities of deoxyadenosine kinase (ATP: deoxyadenosine 5'-phosphotransferase, EC 2.7.1.76) or deoxyadenylate kinase [ATP:(d)AMP phosphotransferase, EC 2.7.4.11]. The activity of 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) was increased 44-fold for AMP and 7-fold for dAMP in B lymphoblasts. A model for the regulation of deoxyadenosine nucleotide synthesis by 5'-nucleotidase activity is proposed on the basis of the observations.
D000243:Adenosine Deaminase / Q000172:deficiency; D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D003839:Deoxyadenosines / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D009708:Nucleotidases / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D003839:Deoxyadenosines; D010770:Phosphotransferases; D009708:Nucleotidases; D000243:Adenosine Deaminase