Pyrimidine metabolism during restorative brain growth after neonatal undernutrition in the rat.

Three litters of 20 Wistar rat pups each were maintained until age 6 days at which time only the 4 lightest and 4 heaviest pups from each litter were left with the mother until age 13 days. Three control litters of eight pups each were also maintained for 13 days. At that time, the undernourished light pups showed body weight, cerebellar weight, and cerebellar DNA, respectively, of 79.2%, 86.6%, and 90.4% compared with a "combined control" group consisting of control pups plus undernourished heavy pups which were statistically indistinguishable with regard to these three measurements. After the week of "catch-up" or restorative body and brain growth, activities of enzymes from metabolic pathways leading to pyrimidine and nucleic acid biosynthesis were measured in cerebella from all three groups (control, undernourished heavy, and undernourished light). The salvage pathway enzyme thymidine kinase (TK) and the inter-conversion pathway enzyme thymidylate synthetase (TS) in the undernourished light group showed significant elevations of 32% and 11%, respectively, above activity in the combined control group. The salvage pathway enzyme uridine kinase (UK) and the de novo pathway enzyme aspartate transcarbamylase were not significantly different in cerebella from these two groups. The significant elevation in TK and TS in undernourished pups suggest that these enzymes are critical for restorative brain growth. The significant elevation of TS indicates that the inter-conversion pathway converting available uridylate, a ribonucleotide, to thymidylate, a deoxyribonucleotide, is activated in order to augment DNA biosynthesis.