Purine synthesis de novo and its regulation in rat hepatocytes.

Purine synthesis de novo and its regulation were studied in freshly isolated hepatocytes from fed adult male rats. The cells incorporated [14C]formate mainly into purine ribonucleotides. The immediate effect of increasing the concentration of inorganic phosphate in the incubation medium was an increase in 5-phosphoribosyl 1-pyrophosphate (PP-ribose-P) availability and a stimulation of purine synthesis de novo. However, prolonged incubation of cells in 25 mM phosphate resulted in a decreased PP-ribose-P availability and purine synthesis de novo. Methylene blue and phenazine methosulfate decreased PP-ribose-P availability and purine synthesis de novo although they stimulated considerably the pentose phosphate pathway. In contrast, epinephrine and glucagon increased significantly PP-ribose-P availability and purine synthesis de novo, but they did not change the activity of the pentose phosphate pathway. These results show a relationship between PP-ribose-P availability and purine synthesis de novo in rat hepatocytes. They emphasize the complexity of the regulation of PP-ribose-P availability.