Thymidylate synthase

Thymidylate synthase

Thymidylate synthetase (EC number|2.1.1.45) [cite web | title = Entrez Gene: TYMS thymidylate synthetase| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7298| accessdate = ] is the enzyme used to generate thymidine monophosphate (dTMP), which is subsequently phosphorylated to thymidine triphosphate for use in DNA synthesis and repair. By means of reductive methylation, deoxyuridine monophosphate (dUMP) and N5,N10-methylene tetrahydrofolate are together used to form dTMP, yielding dihydrofolate as a secondary product.

As an anti-cancer chemotherapy target, thymidylate synthetase can be inhibited by the fluorinated pyrimidine fluorouracil, or certain folate analogues, including most notably raltitrexed (trade name Tomudex).

ee also

* Pyrimidine analogues

References

Further reading

*cite journal | author= Carreras CW, and Santi DV |title=The Catalytic Mechanism and Structure of Thymidylate Synthase |journal=Annual Review of Biochemistry |volume=64 |issue= 1 |pages= 721–762 |year= 1995 |pmid= 7574499 |doi= PBB_Further_reading
citations =
*cite journal | author=Banerjee D, Mayer-Kuckuk P, Capiaux G, "et al." |title=Novel aspects of resistance to drugs targeted to dihydrofolate reductase and thymidylate synthase. |journal=Biochim. Biophys. Acta |volume=1587 |issue= 2-3 |pages= 164–73 |year= 2002 |pmid= 12084458 |doi=
*cite journal | author=Liu J, Schmitz JC, Lin X, "et al." |title=Thymidylate synthase as a translational regulator of cellular gene expression. |journal=Biochim. Biophys. Acta |volume=1587 |issue= 2-3 |pages= 174–82 |year= 2002 |pmid= 12084459 |doi=
*cite journal | author=Chu J, Dolnick BJ |title=Natural antisense (rTSalpha) RNA induces site-specific cleavage of thymidylate synthase mRNA. |journal=Biochim. Biophys. Acta |volume=1587 |issue= 2-3 |pages= 183–93 |year= 2002 |pmid= 12084460 |doi=
*cite journal | author=Peters GJ, Backus HH, Freemantle S, "et al." |title=Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism. |journal=Biochim. Biophys. Acta |volume=1587 |issue= 2-3 |pages= 194–205 |year= 2002 |pmid= 12084461 |doi=
*cite journal | author=Costi MP, Tondi D, Rinaldi M, "et al." |title=Structure-based studies on species-specific inhibition of thymidylate synthase. |journal=Biochim. Biophys. Acta |volume=1587 |issue= 2-3 |pages= 206–14 |year= 2002 |pmid= 12084462 |doi=
*cite journal | author=Lin D, Li H, Tan W, "et al." |title=Genetic polymorphisms in folate- metabolizing enzymes and risk of gastroesophageal cancers: a potential nutrient-gene interaction in cancer development. |journal=Forum of nutrition |volume=60 |issue= |pages= 140–5 |year= 2007 |pmid= 17684410 |doi= 10.1159/0000107090

External links

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