The Relation between Uracil-catabolizing Enzymes and Rate of Rat Liver Regeneration

The degradation of uracil in regenerating rat liver has been investigated by Canellakis et al. (2, 3) and, more recently, by Skijld (4). Uracil labeled with C?4 in the ureido carbon was incubated with rat liver slices (2, 3) and with the particle-free supernatant fraction obtained by centrifugation of rat liver homogenates (4). The formation of CY402 was used as a measure of the breakdown of uracil. In both laboratories it was observed that the capacity of regenerating liver to degrade uracil was lower than that of normal rat liver. Since the breakdown of uracil to p-alanine with the concomitant release of the ureido carbon as COZ is catalyzed by the sequential action of the three enzymes, dihydrouracil dehydrogenase (5, 6)) dihydrouracil hydrase (7), and &ureidopropionic acid decarbamylase (8), the low uracil degradation might be due to a decreased level of at least one of the three enzymes involved in this degradation. In normal liver the level of dihydrouracil dehydrogenase limits the catabolic capacity (6). Canellakis has suggested that the uracil-catabolizing system is part of a mechanism regulating nucleic acid synthesis (2). It was therefore of interest to get a deeper insight into the nature of the variations in catabolic activity observed during liver regeneration. The present work describes studies on the levels of each of the three enzymes involved in the breakdown of uracil to p-alanine at different time intervals after partial hepatectom);.