Evidence for a new step between ATP and 5-amino 4-imidazolcarboxamide ribotide in the cyclic process of histidine biosynthesis

Abstract

Moyed and Magasanik (1960) have shown that the biosynthesis of imidazole ring of histidine occurs from ATP, ribose-5-phosphate (R-5-P) and glutamine in bacteria. The products of the reaction are imidazole glycerol phosphate (IGP) and 5-amino 4-imidazolcarboxamide ribotide (AICAR). They have suggested that the reaction takes place in two steps, separable by protamine fractionation. The first is the addition of R-5-P to ATP to give “compound III” of a hypothetical structure, and the second is the breakage of the purine ring in the presence of glutamine to give AICAR and IGP. The first step has been shown to be inhibited by histidine providing another example of a feedback control. ▪ We have shown previously that histidine depresses the rate of reversion to prototrophy in a heteroallelic ab 3 (adenine and histidine requiring) diploid of baker's yeast ( Luzzati, Clavilier and Slonimski, 1959). The present paper describes the activity of crude extracts of Saccharomyces cerevisiae in forming AICAR and shows, as a consequence of the study of histidine inhibition, that a new supplementary step in the above mentioned reaction has to be postulated to explain the experimental results.