Figure 1.

The schematic illustration of CAD and CAD-mediated de novo synthesis of pyrimidine nucleotides. (A) CAD and its domains are shown with the amino acid numbers. (B) The process of de novo synthesis of pyrimidine nucleotides. The first three steps are catalyzed by a trifunctional, cytoplasmic enzyme known as CAD, an acronym derived from the names of the three activities in this protein: carbamoyl phosphate synthetase, aspartate transcarbamylase, and dihydroorotase. The fourth enzyme is a mitochondrial enzyme, dihydroorotate dehydrogenase (DHODH). Phosphoribosyl 5′-pyrophosphate (PRPP) and orotate are catalyzed by UMP synthetase (UMPS) to produce UMP.