Orotidine5phosphate

Orotidine-5'-phosphate (OMP) is a nucleotide intermediate in de novo pyrimidine biosynthesis. It is formed from orotate and phosphoribosyl pyrophosphate by the enzyme orotate phosphoribosyltransferase and is then decarboxylated to uridine monophosphate (UMP) by orotidine-5'-phosphate decarboxylase.

In many organisms the two enzymatic activities are separate: the orotate phosphoribosyltransferase is encoded by pyrE and the orotidine-5'-phosphate decarboxylase by pyrF in bacteria. In humans and some eukaryotes these activities are combined in a single bifunctional enzyme encoded by UMPS. In yeast, the separate genes URA3 and URA4 encode the decarboxylase and transferase activities, respectively.

Functionally, OMP sits at a key branch point by linking de novo pyrimidine synthesis to the production of UMP, which is subsequently converted to UDP, UTP, and CTP, and also to dTMP via dUMP. The formation of OMP consumes PRPP and releases pyrophosphate; the decarboxylation step releases CO2 and proceeds with a large negative free energy change, helping to pull the pathway forward.

Clinical and research relevance: Deficiencies in human UMPS can cause orotic aciduria with megaloblastic anemia, often treated with uridine supplementation. The OMP synthesis steps are targets of study in antimicrobial and anticancer research, and the enzymes OPRT and ODCase have been extensively studied for catalysis and mechanism.