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Pyrimidine biosynthesis occurs both in the body and through organic synthesis.
De novo biosynthesis of pyrimidine
|carbamoyl phosphate synthetase II||carbamoyl phosphate||This is the regulated step in the pyrimidine biosynthesis.|
|aspartic transcarbamolyase (aspartate carbamoyl transferase)||carbamoyl aspartic acid||-|
|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.|
|uridine-cytidine kinase 2||UDP||Phosphorylation. ATP is used.|
|nucleoside diphosphate kinase||UTP||Phosphorylation. ATP is used.|
|CTP synthase||CTP||Glutamine and ATP are used.|
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, and then to beta-alanine, CO2, and ammonia by beta-ureidopropionase. 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.
Modulating the pyrimidine metabolism pharmacologically has therapeutical uses.
- "Entrez Gene: CAD carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase".
- "Entrez Gene: DHODH dihydroorotate dehydrogenase".
- "Entrez Gene: UMPS uridine monophosphate synthetase".
- "Entrez Gene: UCK2 uridine-cytidine kinase 2".
- Nielsen, HR; Sjolin, KE; Nyholm, K; Baliga, BS; Wong, R; Borek, E (1974). "Beta-aminoisobutyric acid, a new probe for the metabolism of DNA and RNA in normal and tumorous tissue". Cancer Research 34 (6): 1381–4. PMID 4363656.