This MedLibrary.org supplementary page on Pyrimidine metabolism is provided directly from the open source Wikipedia as a service to our readers. Please see the note below on authorship of this content, as well as the Wikipedia usage guidelines. To search for other content from our encyclopedia supplement, please use the form below:
Related Sponsors
 |
This article or section includes a list of references or external links, but its sources remain unclear because it lacks inline citations. You can improve this article by introducing more precise citations where appropriate. (August 2008) |
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".
External links
|
|||||||||||
|
|||||
|
|||||||||||||||||||||||||||
Wikipedia content modification information:
- This page was last modified on 14 October 2008, at 22:01.
Wikipedia Authorship and Review
Wikipedia content provided here is not reviewed directly by MedLibrary.org. Wikipedia content is authored by an open community of volunteers and is not produced by or in any way affiliated with MedLibrary.org.
Wikipedia Usage Guidelines
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article on "Pyrimidine metabolism".
The URL for this specific entry is:
All Wikipedia text is available under the terms of the GNU Free Documentation License. (See Copyrights for details). Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc.