Dihydroorotate Dehydrogenase

Dihydroorotate dehydrogenase (DHODH) is the fourth enzyme in the de novo pyrimidine biosynthesis pathway, serving as the catalyst to oxidize the dihydroorotate to orotic acid in the biosynthesis of uridine monophosphate (UMP). DHODH is a known target for autoimmune diseases as well as an important target for malaria.

Based on localization and electron acceptor, DHODHs have classified into two families: Family 1 members are soluble proteins localized to the cytosol, while family 2 members are membrane proteins localized to the inner mitochondrial membrane. Family 1 is further subdivided into family 1A and family 1B, which use fumarate and NAD+ (respectively) as electron acceptors. Family 2 DHODH enzymes use respiratory quinones as electron acceptors.