Pathway
Pyrimidine biosynthesis
The pyrimidine orotate (orotic acid) is synthesized in a sequence of four reactions, deriving its atoms from glutamine, bicarbonate, and aspartate. A single multifunctional cytosolic enzyme catalyzes the first three of these reactions, while the last one is catalyzed by an enzyme associated with the inner mitochondrial membrane. In two further reactions, catalyzed by a bifunctional cytosolic enzyme, orotate reacts with 1-phosphoribosyl 5-pyrophosphate (PRPP) to yield orotidine 5'-monophosphate, which is decarboxylated to yield uridine 5'-monophosphate (UMP). While several individual reactions in this pathway are reversible, other irreversible reactions drive the pathway in the direction of UMP biosynthesis in the normal cell. All reactions are thus annotated here only in the forward direction.
Continue reading
This pathway has been most extensively analyzed at the genetic and biochemical level in hamster cell lines. All three enzymes have also been purified from human sources, however, and the key features of these reactions have been confirmed from studies of this human material.
All other pyrimidines are synthesized from UMP. The reactions annotaed here, catalyzed by dCMP deaminase and dUTP diphosphatase yield dUMP, which in turn is converted to TMP by thymidylate synthase.
What the reference databases state
Statements
3 statements
3 statements · 1 reference database · Subject: Pyrimidine biosynthesis · Sources: Reactome
- CAD participates in Pyrimidine biosynthesisProteinReactome R-HSA-500753Inferred only
- DHODH participates in Pyrimidine biosynthesisProteinReactome R-HSA-500753Inferred only
- UMPS participates in Pyrimidine biosynthesisProteinReactome R-HSA-500753Inferred only