Dihydroorotate dehydrogenase (Plasmodium) (DHODH)

Dihydroorotate dehydrogenase (DHODH) from Plasmodium species, particularly *Plasmodium falciparum*, is a mitochondrial enzyme essential for de novo pyrimidine biosynthesis. It catalyzes the oxidation of dihydroorotate to orotic acid, utilizing FMN and coenzyme Q as cofactors. As Plasmodium parasites rely exclusively on this pathway for pyrimidine nucleotide synthesis, PfDHODH represents a validated antimalarial drug target. Inhibition of PfDHODH blocks pyrimidine synthesis, halting parasite replication. Selective inhibitors, such as triazolopyrimidines and isoxazolopyrimidines, have been developed and are undergoing clinical development as potential single-dose malaria treatments. A key challenge is achieving high selectivity for PfDHODH over the human homolog to minimize potential toxicity.

Other names

PfDHODHPlasmodium falciparum dihydroorotate dehydrogenase

Inhibition of dihydroorotate dehydrogenase, blocking de novo pyrimidine synthesis