The Effect of the Feedback Inhibitor, CTP, on Subunit Interactions in Aspartate Transcarbamylase

Aspartate transcarbamylase (ATCase) catalyses the first reaction unique to pyrimidine biosynthesis. The product of this reaction is carbamyl aspartate, which is converted via six subsequent steps to the pyrimidine nucleotides, CTP and UTP (Fig. 1). In Escherichia coli the rate of synthesis of pyrimidine nucleotides is not independent of other chemical events in the bacterium, but is coordinated with them by a simple and effective mechanism. The basis of this mechanism is the pronounced sensitivity of ATCase, the first enzyme of the pathway, to inhibition by CTP, one of the endproducts of the pathway. When CTP and the other endproducts are not used (e.g. during slow nucleic acid synthesis) they accumulate and inhibit ATCase, consequently reducing the rate of their own synthesis. On the other hand, when the supply of endproducts is depleted (e.g. by rapid nucleic acid synthesis), there is little inhibition of ATCase and the synthesis of endproducts...