Regulation of purine uptake in normal and neoplastic cells

Purine bases and purine nucleosides pass the cell membrane by facilitated diffusion. For purine bases two different carrier proteins seem to exist. Purine bases are trapped intracellularly immediately after passage of the cell membrane by the action of purine phosphoribosyltransferases (PRTs). Comparison of kinetic data of transport and intracellular enzyme reactions shows that intracellular metabolism is rate limiting for the whole uptake process. Since phosphate stimulates the uptake of bases, limited availability of phosphoribosylpyrophosphate (PRPP) might play a regulatory role. Purine nucleosides apparently enter cells via a common carrier. Of the nucleosides under investigation, only adenosine was taken up in significant amounts. Uptake of adenosine is mainly determined by the ratio of adenosine deaminase (ADA) and adenosine kinase (AK) activities. For uptake of purine nucleotides sequential action of ecto-5'-nucleotidase (ecto-5'-NT), nucleoside carrier and intracellular metabolism is necessary. Cells without ecto-5'-NT activity did not accumulate radioactivity from nucleotides. Proliferating neoplastic cells (K 562 and HL 60 cells) showed enhanced uptake of purine bases and nucleosides, when compared to quiescent cells (erythrocytes and granulocytes). From initial rates of uptake and intracellular enzyme activities it could be concluded that this enhanced uptake was due to alterations of enzyme pattern in the neoplastic cells.