Principles of Biochemistry, Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Biosynthesis of Amino Acids and Nucleotides
Pyrimidine nucleotides are synthesized from aspartate and ribose phosphate

The common pyrimidine NUCLEOTIDES are cytidine 5'-monophosphate (CMP), or cytidylate, and uridine 5'-monophosphate (UMP), or uridylate; their structures contain the pyrimidine bases cytosine and uracil, respectively. The Biosynthesis OF PYRIMIDINE nucleotides (Fig. 22-19) differs somewhat from that of purine nucleotides; in this pathway, the six-membered pyrimidine ring is formed first, and the ribose phosphate moiety is attached subsequently. This process requires carbamoyl phosphate, which also serves as an intermediate in The Urea Cycle (Section 19.7). However, the carbamoyl phosphate required for urea synthesis is produced in the Cell/35.html">Mitochondria by the mitochondrial enzyme carbamoyl phosphate synthetase I, whereas the carbamoyl phosphate utilized in pyrimidine biosynthesis is synthesized in the Cytosol by a distinct isozyme, carbamoyl phosphate synthetase II. Cytosolic carbamoyl phosphate reacts with aspartate to yield N-carbamoylaspartate. This reaction is catalyzed by aspartate transcarbamoylase, one of the most thoroughly studied allosteric Enzymes (Box 9-5); we will discuss it in more detail below. Dehydration of N-carbamoylaspartate by dihydroorotase leads to ring closure, producing L-dihydroorotate, which is subsequently oxidized to form orotic acid, a pyrimidine derivative. The ultimate electron acceptor in this reaction is NAD⁺.

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Fig. 22-19. Pathway of UTP and CTP biosynthesis (via orotidylate formation). PRPP, 5'-phosphoribosyl-1-pyrophosphate.

At this stage, the D-ribose 5-phosphate side chain, provided by 5-phosphoribosyl-1-pyrophosphate, is attached to orotate to yield orotidylate. Orotidylate is then decarboxylated to form uridylate, which is subsequently phosphorylated to UTP; the latter then accepts an amino group from glutamine to be converted into cytidine triphosphate (CTP) (Fig. 22-19).