Capacity of rat liver for pyrimidine synthesis and catabolism during fetal and neonatal development.
The capacity of minces of rat liver to synthesize and degrade pyrimidines during fetal and neonatal development was examined. Pyrimidine synthesis was determined by measuring the rate of incorporation of NaH14CO3 into orotic acid. Pyrimidine catabolism was estimated by measuring the generation of 14CO2 from [2-14C]uridine. The incorporation of [2-14C]uridine into RNA was determined simultaneously with measurements of uridine catabolism. The activity of beta-ureidopropionase, the enzyme which catalyzes the terminal reaction in the dihydropyrimidine catabolic pathway, was also monitored in cell-free extracts of liver throughout the perinatal period. Catabolic activity was detected at the earliest stage of gestation examined (16 days) and rose sharply during fetal development to reach adult levels at birth or shortly thereafter. A similar rise in the activity of beta-ureidopropionase was somewhat delayed when compared with the rise in overall catabolic activity; the enzyme activity at birth was about half the adult level. By way of contrast, the incorporation of NaH14CO3 into orotic acid and [2-14C]uridine into RNA were highest in 16-day fetal liver and declined sharply with fetal and neonatal development. These results demonstrate an appreciable capacity for pyrimidine catabolism in fetal liver, and also contribute to growing evidence that fetal tissues are capable of meeting their pyrimidine requirements through de novo synthesis. The contrast observed between the rate of synthesis of orotic acid and the capacity for pyrimidine degradation throughout perinatal development fits the pattern which has emerged from other studies showing the pathways for the anabolism and catabolism of pyrimidines to be regulated inversely to one another.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D011247:Pregnancy; D011743:Pyrimidines / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains / Q000196:embryology
D011743:Pyrimidines