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).

The synthesis of UMP.

The color scheme is as follows: enzymes, coenzymes, substrate names, inorganic molecules

|- 
|  carbamoyl phosphate synthetase II[1] 

|- 
| aspartic transcarbamolyase (aspartate carbamoyl transferase)[2] 

|- 
| dihhydroorotase[3] 

|- 
| dihydroorotate dehydrogenase[4] (the only mitochondrial enzyme) 

|- 
| orotate phosphoribosyltransferase[5] 

|- 
| OMP decarboxylase[6] 

|- 
| uridine-cytidine kinase 2[7]  

|- 
| nucleoside diphosphate kinase 

|- 
|  CTP synthase 

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-?-alanine. Thymine is broken down into ?-aminoisobutyrate which can be further broken down into intermediates eventually leading into the citric acid cycle.

?-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.

References

External links

• Overview at Queen Mary, University of London

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