On the relative functioning of the pathways for formation of thymidine nucleotides in the regenerating liver and spleen of the rat

Abstract

Experiments were carried out to give information on the relative functioning, in regenerating rat liver and in spleen, of the two possible pathways for the biosynthesis of thymidine nucleotides, namely: Pathway I: uridine monophosphate → deoxyuridine monophosphate → thymidine monophosphate, and Pathway II: uridine monophosphate → cytidine monophosphate → deoxycytidine monophosphate → deoxyuridine monophosphate → thymidine monophosphate. The pyrimidines of ribonucleic acid and deoxyribonucleic acid were labelled by a single injection of [6- 14C]orotic acid in the control rats. In the experimental animals, in addition to the labelled orotic acid, unlabelled cytidine was injected in divided doses before and after the orotic acid injection. It was noted that in the latter series the unlabelled cytidine caused a great decrease in the specific activities of cytidylic acid isolated from ribonucleic acid and of deoxycytidine from deoxyribonucleic acid, of regenerating liver and spleen, reflecting dilutions of the metabolic pools of cytidine nucleotides. In contrast, there was a comparatively small drop in the specific activity of deoxyribonucleic acid-thymidine. It is concluded that in both tissues, thymidine monophosphate is formed from uridine monophosphate to a greater extent through Pathway I without the intermediate formation of cytosine nucleotides stipulated by Pathway II.