Guanine Uptake by Human Erythrocytes

Abstract

It has been clearly established that mature human erythrocytes cannot synthesize de novo purines (1); consequently the turnover of purine nucleotides in red cells must result from the continual entry and release of purines. Hypoxanthine and adenine uptake by human erythrocytes has been studied in our laboratories (2–4). Hypoxanthine uptake is mediated by its incorporation into IMP. The rate of synthesis of this nucleotide is dependent on the intracellular availability of 5-phosphorybosyl-1-pyrophosphate (PPRP) which increases by increasing the concentration of inorganic phosphate (Pi) and by decreasing the pH and/or the oxygen partial tension of the incubation mixture. Human erythrocytes incorporate exogenous adenine into the nucleotide pool even in the presence of a very low intracellular PPRP concentration, insufficient to allow an appreciable uptake of hypoxanthine as IMP. Adenine nucleotide synthesis in Pi-free media is faster at physiological pH and independent of the oxygen partial pressure. Mature human red blood cells, which mount a high rate of dephosphorylation of GMP, depend almost exclusively on guanine salvage for the maintenance of their guanine ribonucleotide pool (5). Guanine uptake by human erythrocytes has not been investigated systematically. In the present paper, the effect of varying Pi concentration on guanine uptake and hypoxanthine release by human erythrocytes has been studied.