Control of purine biosynthesis: I. Release of feedback inhibition by methyl-purines and pyrimidine nucleosides

Abstract

The effect of methyl-purines and pyrimidine nucleosides on utilization of exogenous purines by Escherichia coli has been studied. The differential rates of incorporation into nucleic acids of extracellular sources of nucleic acid purines, labeled with C 14, were measured. The concentrations of exogenous purines used caused immediate maximal feedback inhibition of de novo purine synthesis. The degree of inhibition caused by exogenous free purine bases was not significantly altered by the addition of methyl-purines and pyrimidine nueleosides. However, when the source of cellular purine was a nucleoside, either a methyl-purine or a pyrimidine nucleoside alone restored de novo synthesis significantly. When both were added together, feedback inhibition was almost completely released. Short-time experiments measuring total uptake of labeled purines indicated that both methyl-purines and pyrimidine nucleosides inhibit steps in the synthesis of nucleic acids from exogenous nucleosides before the formation of the allosteric inhibitor. The pyrimidine nucleosides apparently inhibit entry into the cell. Methyl-purines presumably slow down the formation of nucleotides.