DHODH

Dihydroorotate dehydrogenase (DHODH) is a mitochondrial flavoprotein enzyme catalyzing the rate-limiting step of de novo pyrimidine biosynthesis—oxidizing dihydroorotate to orotate using ubiquinone as an electron acceptor. Common aliases include DHOdehase and DHOD. It supports DNA/RNA synthesis and cell proliferation, linking metabolic pathways to cellular growth.
DHODH deficiency causes hereditary orotic aciduria type II (orotic aciduria, megaloblastic anemia). It is a therapeutic target: leflunomide (RA) and teriflunomide (MS) inhibit DHODH. New inhibitors like brequinar are in clinical trials for cancer, exploiting its role in sustaining rapid tumor cell proliferation.