REGULATION AND COORDINATION OF PURINE AND PYRIMIDINE BIOSYNTHESES IN YEAST. I. REGULATION OF PURINE BIOSYNTHESIS AND ITS RELATION TO TRANSIENT CHANGES IN INTRACELLULAR NUCLEOTIDE LEVELS.

The control of purine biosynthesis in a yeast mutant deficient for uracil, adenine, and histidine has been studied in vivo. The adenine mutation causes accumulation of aminoimidazole ribotide in the cells. The control curve relating steady-state purine nucleotide level in the cell to rate of synthesis in the de novo purine synthetic pathway has been determined. Control in the cell depends on a feedback mechanism involving end-product inhibition. The transient responses of the purine nucleotide pool to changes in adenine input have been studied. Under certain conditions the pool overshoots when shifting from one steady-state to another. Transient changes in nucleotide levels are followed by inverse changes in the rate of attempted de novo purine synthesis. A study of the transient responses of specific intracellular nucleotides suggests that inosinic acid controls the rate of attempted purine synthesis. The transient response of nucleic acid synthesis rate to changes in nucleotide levels was studied and the implications for regulation of nucleic acid synthesis discussed.