Salvage Pathways of Pyrimidine Ribonucleotides (Saccharomyces cerevisiae)

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Description

Pyrimidine nucleotides are essential as components of nucleic acids, as substrates for amino acid synthesis and as energy sources, but defects in the de novo biosynthesis of pyrimidines are not lethal in S. cerevisiae cells (CITS:10501935). This is because salvage pathways are able to utilize preformed bases (either from exogenous sources or internal turnover sources) for the synthesis of pyrimidines (CITS:2189783). If the required substrates are available, salvage pathways are preferred over de novo synthesis pathways for pyrimidine biosynthesis (CITS:12111094). The salvage pathways of pyrimidine ribonucleotides consist of 1) importing exogenous bases into the cell, and 2) the interconversion of various bases (CITS:2189783)(CITS:12111094). Three proteins are involved in the import of exogenous bases used by the salvage pathway for pyrimidine ribonucleotide biosynthesis. Uracil enters the cell via the Fur4p uracil permease (CITS:6290876)(CITS:3276521), cytosine enters the cell via the Fcy2p purine-cytosine transporter (CITS:6387700)(CITS:2191181), and uridine enters the cell via the Fui1p uridine permease (CITS:9485596). As with many of the metabolic pathways of S. cerevisiae, the pathways for the salvage of pyrimidine ribonucleotides are under both transcriptional and post-transcriptional catabolite repression at a variety of points (CITS:10074071)(CITS:11125145)(CITS:12111094)(CITS:12570998)(CITS:12791685)(CITS:1429716)(CITS:14657252). This pathway is of biomedical interest because cytosine deaminase (Fcy1p) is not found in mammals (CITS:12637534) and is capable of catalyzing the deamination of the prodrug 5-fluorocytosine (5FC) to form the anticancer drug 5-fluorouracil (5FU) (CITS:15823054). Expression of Fcy1p in tumor cells increases their sensitivity to 5FC, and expression of Fur1p increases tumor cell sensitivity to 5FU (CITS:10919655). Tumor cells expressing a novel chimeric protein, produced from a gene containing the FCY1 and FUR1 coding sequences fused in frame, display significantly increased sensitivity to 5-FC suggesting that this novel suicide gene may constitute an original and potent candidate therapeutic gene for cancer gene therapy (CITS:10919655). SOURCE: SGD pathways, http://pathway.yeastgenome.org/server.html

Comments

GenMAPP remarks 
Based on http://pathway.yeastgenome.org/biocyc/

Ontology Tags

 

Bibliography

  1. Kurtz JE, Exinger F, Erbs P, Jund R; ''New insights into the pyrimidine salvage pathway of Saccharomyces cerevisiae: requirement of six genes for cytidine metabolism.''; Curr Genet, 1999 PubMed
  2. Kurtz JE, Exinger F, Erbs P, Jund R; ''The URH1 uridine ribohydrolase of Saccharomyces cerevisiae.''; Curr Genet, 2002 PubMed

History

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CompareRevisionActionTimeUserComment
70054view06:03, 12 July 2013EgonwMarked a few DataNodes with CAS registry numbers as metabolites.
69595view20:31, 8 July 2013MaintBotUpdated to 2013 gpml schema
67632view11:36, 26 June 2013DdiglesOntology Term : 'pyrimidine salvage pathway' added !
56270view14:26, 5 January 2013EgonwConnecting dots.
41824view04:49, 2 March 2011MaintBotRemoved redundant pathway information and comments
36656view22:40, 9 April 2010MaintBotDescription and bibliography added from SGD
20881view11:30, 14 November 2008MaintBot[[Pathway:Saccharomyces cerevisiae:Salvage Pathways of Pyrimidine Ribonucleotides]] moved to [[Pathway:WP95]]: Moved to stable identifier
12839view08:05, 17 May 2008MaintBotautomated metabolite conversion
8915view14:12, 7 January 2008MaintBotAdded to category $category
8913view14:12, 7 January 2008M.BraymerUploaded new pathway

External references

View all...
NameTypeDatabase referenceComment
ADPMetabolite58-64-0 (CAS)
cytidineMetabolite65-46-3 (CAS)
FUR1GeneProductS000001170 (SGD)
FCY1GeneProductS000006266 (SGD)
CDD1GeneProductS000004235 (SGD)
riboseMetabolite50-69-1 (CAS)
URH1GeneProductS000002808 (SGD)
GDPMetabolite146-91-8 (CAS)
URK1GeneProductS000005295 (SGD)
pyrophosphateMetabolite2466-09-3 (CAS)
YNK1GeneProductS000001550 (SGD)
uridineMetabolite58-96-8 (CAS)
cytosineMetabolite71-30-7 (CAS)
ATPMetabolite1927-31-7 (CAS)
uracilMetabolite66-22-8 (CAS)
GTPMetabolite2564-35-4 (CAS)
PRPPMetabolite97-55-2 (CAS)
CDPMetabolite63-38-7 (CAS)
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