Figure 1.

De novo biosynthesis of pyrimidines. Biosynthesis of UMP takes place in six steps and is catalyzed by three enzymes in humans. The first three transformations that put together carbonate, ATP, the nitrogen from glutamine, and aspartate to yield dihydroorotate, are catalyzed by the enzyme CAD. CAD is composed of three enzymatic domains including carbamoyl phosphate synthase II (CPS-II), aspartic transcarbamoylase (ATCase, aspartate carbamoyl transferase), and dihydroorotase (DHOase). The next step in the pathway is catalyzed by dihydroorotate dehydrogenase (DHOD), which is the only mitochondrial protein in the pathway. The final two chemical transformations are catalyzed by UMP synthase (UMPS), which is composed of an orotate phosphoribosyltransferase (OPRT) domain and an orotidine monophosphate decarboxylase (OMPDC) domain. CAD, carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase; UMP, uridine 5′-monophosphate.