Dependence of adenine production upon polyamine synthesis in cultured human lymphoblasts

Biochim Biophys Acta. 1981 Jul 17;675(3-4):344-50. doi: 10.1016/0304-4165(81)90024-6.


The exact source of de novo adenine produced by mammalian cells remain poorly understood, and this prompted the present study. Using a human lymphoblastoid cell line (WI-L2) deficient in adenine phosphoribosyltransferase (EC, we have quantitated the rate of adenine synthesis and the relative importance of the phosphorolysis of 5'-methylthioadenosine versus adenosine or 2'-deoxyadenosine in adenine generation. Dividing adenine phosphoribosyltransferase-deficient WI-L2 cells produced adenine at a rate of 0.27 nmol/mg protein/h. This represented approximately 10% of the rate of hypoxanthine production by WI-L2 cells deficient in hypoxanthine phosphoribosyltransferase (EC but was equivalent to the rate of 5'-methylthioadenosine synthesis by human lymphoblastoid CCRF-CEM deficient in 5'-methylthioadenosine, phosphorylase (5'-methylthioadenosine: orthophosphate methylthioribosyltransferase). Up to 97% of adenine, but not hypoxanthine, synthesis was inhibited dose-dependently by the S-adenosylmethionine decarboxylase-inhibitor methylglyoxal bis(guanylhydrazone) and also by spermidine and spermine, but was enhanced by putrescine. The addition of 2-fluoroadenine, a potent competitive inhibitor of methylthioadenosine phosphorylase (Ki = 0.43 microM) to adenine phosphoribosyl-transferase-deficient cells resulted in a progressive accumulation of 5'-methylthioadenosine in the culture medium, and up to an 85% decrease in adenine production at non-toxic concentrations. These results show that de novo adenine synthesis by dividing human cells is considerable, and that 85-97% derives from the cleavage of 5'-methylthioadenosine and hence from polyamine synthesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine / biosynthesis*
  • Adenine Phosphoribosyltransferase / deficiency
  • Adenosine / analogs & derivatives
  • Adenosine / deficiency
  • Adenosylmethionine Decarboxylase / antagonists & inhibitors
  • Cells, Cultured
  • Genetic Variation
  • Humans
  • Hypoxanthine Phosphoribosyltransferase / deficiency
  • Leukemia, Lymphoid / metabolism
  • Polyamines / biosynthesis*
  • Purine-Nucleoside Phosphorylase / deficiency
  • Putrescine / biosynthesis
  • Spermidine / biosynthesis
  • Spermine / biosynthesis
  • Spleen / metabolism
  • Thionucleosides / deficiency


  • Polyamines
  • Thionucleosides
  • Spermine
  • Purine-Nucleoside Phosphorylase
  • 5'-methylthioadenosine phosphorylase
  • Adenine Phosphoribosyltransferase
  • Hypoxanthine Phosphoribosyltransferase
  • Adenosylmethionine Decarboxylase
  • Adenine
  • Adenosine
  • Spermidine
  • Putrescine