Uridine monophosphate (de novo pyrimidine synthesis)

Route: Carbamoyl phosphate + Aspartate → N-Carbamoyl-aspartate → Dihydroorotate → Orotate + 5-Phosphoribosyl 1-pyrophosphate → Orotidine 5'-monophosphate → Uridine monophosphate

Unlike the purines, the pyrimidine ring is built free and joined to ribose phosphate late. Carbamoyl phosphate, made here from glutamine, bicarbonate and two ATP, adds to the amino group of aspartate. The ring then closes and is oxidized to orotate. Orotate takes ribose phosphate from PRPP, and a last decarboxylation gives UMP. In humans the first three enzymes are three domains of one large protein, CAD, and the last two are two domains of one protein, UMP synthase. Dihydroorotate dehydrogenase is a separate enzyme on the inner mitochondrial membrane. It hands its electrons to ubiquinone (coenzyme Q), shown here as the electron acceptor in place of NAD⁺, and ubiquinone passes them on to the respiratory chain. The carbamoyl phosphate here is made by CPS II. The urea cycle uses a different enzyme, CPS I, that starts from ammonium. The drawn structure of CPS is the E. coli enzyme (1BXR). Its reaction is the same.

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Steps

Enzyme names and EC numbers are those used on the interactive board. Checked against sources: see the claim table in the repository (tools/pathway_data/checks).