Purine and pyrimidine nucleotide concentrations in cells with decreased hypoxanthine-guanine-phosphoribosyltransferase (HGPRT) activity.

1. In order to investigate the role of purine ribonucleotides in the regulation of de novo purine synthesis in living human cells deficient in HGPRT, intracellular ribonucleotide concentrations have been measured in HGPRT lymphoblasts, fibroblasts and erythrocytes and in appropriate HGPRT controls by high pressure liquid chromatography. 2. Purine Purine ribonucleotide concentrations were not reduced in HGPRT cells, supporting the hypothesis that accelerated purine biosynthesis de novo results from increased availability of PP-ribose-P and not from altered feedback regulation by purine ribonucleotides in HGPRT deficient cells. 3. Striking increases in intracellular concentrations of some pyrimidine nucleotides and nucleotide sugars were detected in HGPRT lymphoblasts and erythrocytes, but not in fibroblasts. 4. The possibiiity that this abnormality of pyrimidine metabolism might result from coordinate regulation of purine and pyrimidine synthesis de novo by PP-ribose-P was not substantiated by measurements of rates of pyrimidine synthesis and experimental elevation of intracellular concentrations of PP-ribose-P following incubation of cells with inorganic phosphate.