Multiple mechanisms of regulation of purine biosynthesis de novo in intact tumor cells

Abstract

Purine biosynthesis de novo is inhibited when Ehrlich ascites tumor cells are incubated with purine bases, and this study has attempted to evaluate several possible mechanisms by which this inhibition might be achieved. Measurements of amidophosphoribosyltransferase (EC 2.4.2.14) activity under conditions where purine nucleotide concentrations had been increased by prior incubation of the tumor cells with purine bases, have revealed that this activity is not inhibited under these conditions. Inhibition of purine biosynthesis de novo may be due, in large part, simply to the lowering of 5-phosphoribosyl-1-pyrophosphate concentrations that result from the use of 5-phosphoribosyl-1-pyrophosphate for purine nucleotide synthesis via the purine phosphoribosyltransferases. Other factors, such as inhibition of 5-phosphoribosyl-1-pyrophosphate synthesis by elevated purine nucleotide concentrations, and competition between amidophosphoribosyl-transferase and the purine phosphoribosyltransferases for 5-phosphoribosyl-1-pyrophosphate, have also been shown to decrease the rate of purine biosynthesis de novo in intact Ehrlich ascites tumor cells.