Stereochemistry of catabolism of the RNA base uracil

Abstract

A mammalian enzyme system has been used to study the stereochemistry of the catabolism of the pyrimidine uracil (1) to the amino acid β-alanine (4). Use of [5-²H]- and [6-²H]-uracils and of ²H₂O in the incubations yielded stereospecifically deuteriated samples of β-alanine. Assays, involving total synthesis of samples of β-alanine unambiguously labelled with deuterium in each of the four C–H bonds have shown that, in the first step in the catabolic process, uracil is reduced by dihydrouracil dehydrogenase with overall anti addition of hydrogen, at the si face at C-6 and the si face at C-5.