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Pyrimidine biosynthesis occurs both in the body and through organic synthesis.
Contents |
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 II1 | carbamoyl phosphate | This is the regulated step in the pyrimidine biosynthesis. |
| aspartic transcarbamolyase (aspartate carbamoyl transferase)2 | carbamoyl aspartic acid | - |
| dihhydroorotase3 | dihydroorotate | Dehydration |
| dihydroorotate dehydrogenase4 (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 phosphoribosyltransferase5 | OMP | PRPP is used. |
| OMP decarboxylase6 | UMP | Decarboxylation |
| uridine-cytidine kinase 27 | 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.citation needed
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
- ^ "Entrez Gene: CAD carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase".
- ^ "Entrez Gene: CAD carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase".
- ^ "Entrez Gene: CAD carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase".
- ^ "Entrez Gene: DHODH dihydroorotate dehydrogenase".
- ^ "Entrez Gene: UMPS uridine monophosphate synthetase".
- ^ "Entrez Gene: UMPS uridine monophosphate synthetase".
- ^ "Entrez Gene: UCK2 uridine-cytidine kinase 2".
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Wikipedia content modification information:
- This page was last modified on 14 October 2008, at 22:01.
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