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). Both autoimmune diseases and malaria have been known to be affected by DHODH.
DHODHs are divided into two families based on localization and the electron acceptor: While family 2 members are membrane proteins localized to the inner mitochondrial membrane, family 1 members are soluble proteins localized to the cytosol. Families 1A and 1B, which use fumarate and NAD+ as their respective electron acceptors, are further divided into families 1. Respiratory quinones are used by DHODH enzymes in family 2 as electron acceptors.