Regulation of pyrimidine biosynthesis and its strong coupling to the purine system.

The control of pyrimidine biosynthesis in a yeast mutant deficient for uracil, adenine, and histidine has been studied in vivo. The uracil mutation causes accumulation of ureidosuccinic acid and dihydroorotic acid in the cells. Accumulation is prevented when the pyrimidine nucleotide level in the cell is raised, apparently owing to feedback inhibition in the pyrimidine system. Investigation of the coupling of purine and pyrimidine systems shows that a high level of purine nucleotides can reverse inhibition in the pyrimidine internal feedback loop. Under certan conditions this reversal may affect only the first step of the pyrimidine system so that ureidosuccinic acid is synthesized and the next element of the pyrimidine pathway, dihydroorotic acid, is not synthesized. Other aspects of coupling between the pyrimidine system and other systems are presented.