Pyrimidine synthesis

Pyrimidine metabolism

Pyrimidine biosynthesis occurs both in the body and through organic synthesis.

De novo biosynthesis of pyrimidine

Unlike purines, pyrimidines are assembled before being attached to 5-phosphoribosyl-1-pyrophosphate (PRPP).

Enzyme Product Description
carbamoyl phosphate synthetase II carbamoyl phosphate This is the regulated step in the pyrimidine biosynthesis.
aspartic transcarbamolyase (aspartate carbamoyl transferase carbamoyl aspartic acid -
dihhydroorotase dihydroorotate Dehydration
dihydroorotate dehydrogenase (the only mitochondrial enzyme) orotate Dihydroorotate then enters the mitochondria where it is oxidised through removal of hydrogens. This is the only mitochondrial step in nucleotide rings biosynthesis.
orotate phosphoribosyltransferase OMP PRPP is used.
OMP decarboxylase UMP Decarboxylation
nucleoside monophosphate kinase UDP Phosphorylation. ATP is used.
nucleoside diphosphate kinase UTP Phosphorylation. ATP is used.
CTP synthase CTP Glutamine and ATP are used.

The first three enzymes are all coded by the same gene in Metazoa (CAD). In Fungi, a similar protein exists but lacks the dihydroorotase function: another protein catalyzes the second step.

In other organisms (Bacteria, Archaea and the other Eukaryota), the first three steps are done by three different enzymes.

Pyrimidine catabolism

Pyrimidines are ultimately catabolized (degraded) to CO2, H2O, and urea. Cytosine can be broken down to uracil which can be further broken down to N-carbamoyl-β-alanine. Thymine is broken down into β-aminoisobutyrate which can be further broken down into intermediates eventually leading into the citric acid cycle.

β-aminoisobutyrate acts as a rough indicator for rate of DNA turnover.

Pharmacotherapy

Modulating the pyrimidine metabolism pharmacologically has therapeutical uses.

Pyrimidine synthesis inhibitors are used in active moderate to severe rheumatoid arthritis and psoriatic arthritis. Examples include Leflunomide.

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