Plasmodium vivax dihydroorotate dehydrogenase (PvDHODH)

Plasmodium vivax dihydroorotate dehydrogenase (PvDHODH) is a mitochondrial enzyme that catalyzes the fourth step of the de novo pyrimidine biosynthetic pathway, specifically the oxidation of dihydroorotate to orotate. This reaction is essential for the parasite because, unlike human cells, Plasmodium species lack the machinery to salvage preformed pyrimidines from the host and must rely entirely on de novo synthesis for DNA and RNA production. The enzyme is functionally linked to the mitochondrial electron transport chain as it utilizes ubiquinone as an electron acceptor. Due to significant structural differences between the parasite enzyme and the human ortholog, PvDHODH serves as a high-priority target for the development of selective antimalarial drugs. Inhibitors such as DSM265 and DSM421 have shown efficacy in targeting both the blood and liver stages of the parasite, which is critical for treating P. vivax due to its ability to form dormant hypnozoites. Targeting PvDHODH provides a potent mechanism to inhibit parasite replication and potentially prevent disease relapse.

Other names

Dihydroorotate dehydrogenase (quinone)Dihydroorotate oxidaseDHODHPvDHOD

Inhibition of the de novo pyrimidine biosynthetic pathway by binding to the ubiquinone-binding site of dihydroorotate dehydrogenase, leading to the depletion of pyrimidine nucleotides required for DNA and RNA synthesis.