orotidine

Orotidine is the ribonucleoside formed when orotic acid is linked to a ribose sugar by a glycosidic bond. It is a member of the pyrimidine nucleosides and functions as an intermediate in the metabolism and salvage of pyrimidines.

In cellular metabolism, orotate can be converted to orotidine-5'-phosphate (OMP) by orotate phosphoribosyltransferase, using phosphoribosyl pyrophosphate as the ribose phosphate donor. OMP is subsequently decarboxylated to uridine monophosphate (UMP) by orotidine-5'-phosphate decarboxylase. In many organisms these two enzymatic activities are separate enzymes; in humans, the two activities are combined in a single bifunctional enzyme called UMPS.

Orotidine itself can be formed by condensation of orotate with ribose and participates in the pyrimidine salvage pathway, but in most mammalian cells uridine is the more prominent nucleoside, and orotidine is not typically a major metabolic endpoint.

Clinical relevance: Defects in the enzymes responsible for converting orotate to UMP, such as UMPS, can cause orotic aciduria, a rare metabolic disorder characterized by megaloblastic anemia and growth retardation. Treatment with high-dose uridine can bypass the block by supplying downstream pyrimidines.

Orotidine is related to other pyrimidine metabolism components, including orotic acid, uridine, and the broader pathways of de novo and salvage pyrimidine synthesis.