Dihydroorotate Dehydrogenase

Dihydroorotate dehydrogenase (DHODH) is an essential enzyme in the de novo synthesis pathway of pyrimidine nucleotides, which are vital components of DNA and RNA. This enzyme catalyzes the conversion of dihydroorotate to orotate, with the simultaneous reduction of flavin mononucleotide to FMNH2. Located in the mitochondrial inner membrane, DHODH plays a key role in cellular proliferation and metabolism, particularly in rapidly dividing cells. Because of its critical function in nucleotide synthesis, DHODH is targeted by drugs such as leflunomide, used primarily in the treatment of rheumatoid arthritis and other autoimmune diseases. By inhibiting DHODH, these medications effectively suppress immune cell proliferation and function.