Purine nucleotide cycles and their metabolic role.

The enzymatic reactions responsible for the interconversion of purine nucleotides and for the biosynthesis of the imidazole ring of histidine in bacteria have been described previously (4-7). This study of the isolated enzymes not only revealed the chemical nature of the reactions but also suggested mechanisms for their regulation. The study of purine metabolism described in the present paper was carried out with intact, growing cells. The method used was to observe the utilization of purine bases and of histidine by mutants blocked in different steps of the pathways leading to AMP and GMP. The results of this investigation demonstrate that the mechanisms of biosynthesis and regulation suggested by the studies with isolated enzyme systems are, indeed, operative in the growing cell. The purine ribonucleotides participate in a cyclic pathway whose function is the biosynthesis of histidine and whose oprrrttion is controlled by histidine. Other cycles controlled by ATf’ and by GMP link IMP, AMP, and GMP. It should be pointed out that the studies described here were carried out simultaneously with, and frequently before, the enzymatic studies; the combinat.ion of these experimental tcchniques was invaluable for developing a coherent picture of purine metabolism.