Pyrimidine Biosynthesis de Novo in Skin

The orotic acid pathway was shown to function in the biosynthesis de novo of pyrimidine nucleotides in newborn to 4-day-old mouse skin in vitro. The pathway was established with the use of NaH14CO3, carbamylaspartate-ureido-14C, and orotic acid-2-14C. The labeled carbon in each of the three compounds was incorporated into position C-2 of uracil. In addition, NaH14CO3 was incorporated into carbamylaspartate, orotic acid, and 3'-UMP and 3'-CMP of RNA. Exogenously added carbamylaspartate inhibited the formation of orotic acid from bicarbonate. Carbamylaspartate was converted to orotic acid, and both of these compounds were incorporated into 3'-UMP and 3'-CMP of skin RNA.