Regulation of Amino Acid and Nucleotide Biosynthesis in Yeast

INTRODUCTION In this paper we attempt to summarize the current status of our knowledge of regulation of anabolic pathways. The discussion includes pathways of biosynthesis of all 20 amino acids, of purine and pyrimidine nucleotides, and of single carbon metabolism. Some discussion is devoted to the pathways themselves. We consider this essential, for, in our opinion, doubt exists as to what the actual pathway of synthesis is for some metabolites (e.g., methionine and cysteine). We have also devoted some attention to assignment of genetic blocks. For many genes, assignment is based on enzyme assay, but for a substantial number, assignments are based on indirect evidence such as accumulations and feeding tests. Regulation of biosynthesis occurs at two levels: the regulation of enzyme formation by control of gene expression and the regulation of enzyme activity that controls flow of metabolites. It seems likely that an essential aspect of the latter control is the regulation of the flow of metabolites between compartments of the cell. Substantial portions of the intracellular amino acids are compartmentalized within the cell, largely in the vacuole (for review, see Wiemken 1980; also see Messenguy et al. 1980). Redistribution of amino acids between compartments in response to metabolic signals has been demonstrated (Messenguy et al. 1980; Wiemken 1980). To what extent compartmentalization of metabolites may play a role in regulation for pathways other than amino acid biosynthesis is unknown. Compartmentalization within the mitochondrion has also been demonstrated for some anabolic enzymes. Only for the arginine and branched-chain amino...