De Novo Pyrimidine Nucleotide Synthesis

Abstract

The pathway of biosynthesis of pyrimidine nucleotides de novo from central metabolic intermediates is the same in all prokaryotic and eukaryotic organisms in which it has been examined, but as will be seen, the functional organization of the enzymes of the pathway and the means adopted for regulation of pyrimidine biosynthesis vary greatly from species to species. The primary structures of all of the enzymes of de novo UMP biosynthesis from Bacillus subtilis are known because the genes encoding them have been sequenced. General properties of each of the enzymes have also been determined in studies with crude extracts, but only aspartate transcarbamylase has been purified to homogeneity and characterized in detail. General properties of the enzymes and genes encoding them are summarized. Further detail, with emphasis on the properties that distinguish the B. subtilis enzymes from their homologs in other species, follows. Enzymes of pyrimidine biosynthesis are inactivated in starving cells. Enzymes of purine and amino acid biosynthesis are also inactivated under the same conditions. The genes and enzymes of pyrimidine biosynthesis have not been extensively investigated in other grampositive species. A brief overview of pyrimidine biosynthesis in E. coli and S. typhimurium, with emphasis on points of difference with B. subtilis is described. Regulation of plant carbamylphosphate synthetase invitro resembles regulation of the E. coli enzyme in many ways. The plant enzyme is inhibited by uridine nucleotides and activated by the purine nucleotides IMP, ITP, GMP, and GTP.