Induction of Inosine F-Phosphate Dehydrogenase and Xanthosine S-Phosphate Aminase by Ribosyl-4-

Examination of various purine-requiring mutants of Escherichia coli strain B revealed that one strain, B-35-2, blocked in the conversion of 5-amino-1-(5’-phosphoribosyl)-4-imidazole carboxamide to inosine 5’-phosphate, possessed markedly elevated levels of inosine 5’-phosphate dehydrogenase and xanthosine 5’-phosphate aminase when grown under conditions of purine limitation (1). In contrast, another mutant, B-22, blocked in an earlier step of purine synthesis, produced only moderately elevated enzyme levels under these same conditions. Further investigation of this locational effect revealed that it could be attributed to the dephosphorylated product of phosphoribosyLAIC,1 ribosyl-AIC, which accumulated in the medium of strain B-35-2. The addition of this compound to cultures of purine-requiring mutants with early blocks stimulated the production of both the aminase and the dehydrogenase. These observations suggested that ribosyl-AIC might have an effect on the regulation of the two enzymes. Since the intracellular level of GMP or one of its derivatives has been shown to control the production of both IMP dehydrogenase (2) and XMP aminase (3) through repression, it was of interest to consider the possibility that ribosyl-AIC might act by interfering with repressor formation. This could result from an inhibition by ribosyl-AIC of the conversion of GNP to the active form of the repressor or from inhibition of the biosynthesis of GMP itself. Accordingly, the present study on the effect of ribosyl-AIC on purine metabolism was undertaken.