Dihydroorotate dehydrogenase (EC 126.96.36.199) is an enzyme that catalyzes the fourth step in the de novo biosynthesis of pyrimidine. It catalyses the oxidation of dihydroorotate to orotate:
- (S)-dihydroorotate + O2 <math>\rightleftharpoons</math> orotate + H2O2
Human dihydroorotate dehydrogenase is a ubiquitous FMN flavoprotein. In bacteria (gene pyrD), it is located on the inner side of the cytosolic membrane. In some yeasts, such as in Saccharomyces cerevisiae (gene URA1), it is a cytosolic protein, whereas, in other eukaryotes, it is found in the mitochondria.
The immunomodulatory drugs teriflunomide and leflunomide have been shown to inhibit DHODH. Human DHODH has two domains: an alpha/beta-barrel domain containing the active site and an alpha-helical domain that forms the opening of a tunnel leading to the active site. Leflunomide has been shown to bind in this tunnel. Leflunomide is being used for treatment of rheumatoid and psoriatic arthritis.
Mutations in this gene have been shown to cause Miller syndrome  also known as Genee-Wiedemann syndrome, Wildervanck-Smith syndrome or post axial acrofacial dystosis (POADS).
Model organisms have been used in the study of DHODH function. A conditional knockout mouse line called Dhodhtm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping
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This article incorporates text from the public domain Pfam and InterPro IPR001295
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