Pyrimidine biosynthesis occurs both in the body and through organic synthesis.
Contents
De novo biosynthesis of pyrimidine[edit]
carbamoyl phosphate synthetase II[1] | carbamoyl phosphate | This is the regulated step in the pyrimidine biosynthesis. |
aspartic transcarbamolyase (aspartate carbamoyl transferase)[1] | carbamoyl aspartic acid | - |
dihhydroorotase[1] | dihydroorotate | Dehydration |
dihydroorotate dehydrogenase[2] (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[3] | OMP | PRPP is used. |
OMP decarboxylase[3] | UMP | Decarboxylation |
uridine-cytidine kinase 2[4] | 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[edit]
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.[5]
Pharmacotherapy[edit]
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 and Teriflunomide.
References[edit]
- ^ a b c "Entrez Gene: CAD carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase".
- ^ "Entrez Gene: DHODH dihydroorotate dehydrogenase".
- ^ a b "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.
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