Feedback onhibition of uridine kinase by cytidine triphosphate and uridine triphosphate

Abstract

Uridine kinase was found to be the rate-limiting step in the anabolism of uridine to its successive nucleotide derivatives. This enzymatic activity was susceptible to feedback inhibition by the pyrimidine nucleoside triphosphate end-products; effective inhibition was exerted by UTP and even more strikingly by CTP. The analog nucleoside triphosphates, azauridine triphosphate and fluorouridine triphosphate, mimicked the normal compound in exerting inhibition. The inhibition could be partially reversed by higher levels of either uridine or ATP-Mg²⁺. The phosphorylation of cytidine to its nucleotide derivatives was similarly inhibited by both CTP and UTP. Thus, feedback control over salvage pathways for pyrimidine ribonucleotide biosynthesis has been demonstrated.