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词条 Pyrimidine metabolism
释义

  1. De novo biosynthesis of pyrimidine

  2. Pyrimidine catabolism

  3. Pharmacotherapy

  4. References

  5. External links

{{more footnotes|date=August 2008}}

Pyrimidine biosynthesis occurs both in the body and through organic synthesis.

De novo biosynthesis of pyrimidine

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

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

Modulating the pyrimidine metabolism pharmacologically has therapeutical uses.

Pyrimidine synthesis inhibitors are used in active moderate to severe rheumatoid arthritis and psoriatic arthritis, as well as in multiple sclerosis. Examples include Leflunomide and Teriflunomide.

References

1. ^1 2 {{cite web | title = Entrez Gene: CAD carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=790| accessdate = }}
2. ^{{cite web | title = Entrez Gene: DHODH dihydroorotate dehydrogenase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1723| accessdate = }}
3. ^1 {{cite web | title = Entrez Gene: UMPS uridine monophosphate synthetase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7372| accessdate = }}
4. ^{{cite web | title = Entrez Gene: UCK2 uridine-cytidine kinase 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7371| accessdate = }}
5. ^{{cite journal|pmid=4363656|year=1974|last1=Nielsen|first1=HR|last2=Sjolin|first2=KE|last3=Nyholm|first3=K|last4=Baliga|first4=BS|last5=Wong|first5=R|last6=Borek|first6=E|title=Beta-aminoisobutyric acid, a new probe for the metabolism of DNA and RNA in normal and tumorous tissue|volume=34|issue=6|pages=1381–4|journal=Cancer Research}}

External links

  • Overview at Queen Mary, University of London
{{MetabolismMap}}{{Protein metabolism}}{{Nucleotide metabolism}}{{Purinergics}}{{portal bar|Metabolism}}

2 : Pyrimidines|Metabolism
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