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 a mitochondrial enzyme. 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). These reactions have been very well studied in mammals, including humans (Jones 1980). The chicken enzymes are known only as predicted gene products of open reading frames identified through sequencing of the chicken genome and high-throughput mRNA sequencing, and all molecular details of the chicken reactions described here are inferred from those of their human counterparts.
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