dihydroorotase

Dihydroorotase, also known as OPRT, is an enzyme that catalyzes the conversion of carbamoyl phosphate and aspartate to dihydroorotate. This reaction is a crucial step in the de novo synthesis of pyrimidine nucleotides, which are essential building blocks for DNA and RNA. Dihydroorotase is a member of the metalloenzyme family, requiring a metal ion cofactor, typically zinc, for its catalytic activity. It is found in the cytoplasm of eukaryotic cells and in the periplasm of bacteria.

The enzyme plays a key role in the pyrimidine biosynthesis pathway, which is conserved across many organisms. In humans, dihydroorotase is encoded by the *DHODH* gene, although it's important to note that the gene name *DHODH* actually encodes dihydroorotate dehydrogenase, which is a separate enzyme involved in a subsequent step of the pathway. The gene encoding dihydroorotase in humans is *UMPC*. Aberrations in pyrimidine metabolism, including those involving dihydroorotase, can lead to various developmental disorders and diseases.

Dihydroorotase is structurally conserved, with a characteristic beta-lactamase fold. The active site of the enzyme binds the substrates carbamoyl phosphate and aspartate, facilitating the cyclization reaction. The enzyme's function is vital for cell proliferation and survival, making it a potential target for therapeutic interventions. For instance, inhibitors of dihydroorotase could potentially be used to treat cancers or autoimmune diseases by limiting the supply of pyrimidines needed by rapidly dividing cells.