Human blood platelets were found to carry the complete pathway of de novo purine nucleotide synthesis. The rate of purine synthesis was gauged by the rate of incorporation of precursor (¹⁴C)formate into purines. The effect on formate incorporation of several compounds known to inhibit purine synthesis de novo was studied. Adenine, orotic acid and azaserine inhibited purine synthesis, but hypoxanthine and allopurinol did not. Platelet content of phosphoribosylpyrophosphate (PRPP) and of ribose-5-phosphate (R-5-P) was found to be similar to that in human blood leukocytes and erythrocytes. Incubation of intact platelets with high inorganic phosphate concentrations caused an increase in platelet PRPP content but did not affect R-5-P content or the rate of purine synthesis de novo.

Human blood platelets were gtudied for the presence of the pathway of de novo synthesis of purine nucleotides. 8 x 108 cells were incubated for 2.5 h at 37°C in 2 ml of Eagle’s Minimal Essential Medium containing Earle’s Balanced Salt Solution, 15% fetal calf serum and 20 μCi sodium [14C] formate (59 mCi/mmole). Platelets were found to incorporate 14C into total purines at a slow but detectable rate of 50–70 pmoles/8 x 108 cells/2.5 h. This incorporation was inhibited by approximately 80% at 10 mM azaserine and by 60% at 0.1 mM adenine. Adenine is known to affect the rate of purine synthesis de novo through the activity of phosphoribosylpyrophosphate amidotransferase, the first committed enzyme of this pathway. The results suggest the presence of the complete pathway of de novo synthesis of purine nucleotides in normal human peripheral blood platelets.