A glutamine-dependent enzyme for the synthesis of carbamyl phosphate for pyrimidine biosynthesis in fetal rat liver.

Experiments with the soluble supernatant fraction of fetal rat liver indicate that it contains a glutamine-dependent carbamyl phosphate synthetase. This enzyme can utilize ammonia or glutamine as substrate, but the K, for glutamine is low (approximately low5 M) while the Km for ammonium ion-ammonia is at least 100 times higher. The ATP saturation curve for the enzyme appears to be sigmoidal. The pH optimum is 7.4. Glutamine analogues inhibit the ability of either glutamine or ammonia to serve as substrate. Comparisons of the change in the amounts of the glutamine-dependent carbamyl phosphate synthetase and aspartate transcarbamylase in the soluble fraction of the cell and in the amounts of acetylglutamate-dependent carbamyl phosphate synthetase and ornithine transcarbamylase in the particulate fraction of the cell with development from 4 days prior to gestation to 2 days after birth are reported. They suggest that the new enzyme provides carbamyl phosphate for the pyrimidine pathway. The same enzyme activity has also been found in the soluble fraction of a pigeon liver homogenate.