• In enzymology, a thymidylate synthase (FAD) (EC 2.1.1.148) is an enzyme that catalyzes the chemical reaction 5,10-methylenetetrahydrofolate + dUMP + FADH2 ⇌ {\displaystyle \rightleftharpoons } dTMP + tetrahydrofolate + FAD The 3 substrates of this enzyme are 5,10-methylenetetrahydrofolate, dUMP, and FADH2, whereas its 3 products are dTMP, tetrahydrofolate, and FAD. (wikipedia.org)
  • Most organisms, including humans, use the thyA- or TYMS-encoded classic thymidylate synthase whereas some bacteria use the similar flavin-dependent thymidylate synthase (FDTS) instead. (wikipedia.org)
  • We investigated the clinical significance of E2F1 gene expression in relation to its target genes, thymidylate synthase ( TS ) and Survivin , in case of non-small-cell lung cancer (NSCLC). (aacrjournals.org)
  • 5-FdUMP inhibits thymidylate synthase (key enzyme in DNA synthesis), which leads to accumulation of dUMP, which then gets misincorporated into the DNA in the form of 5-FdUTP resulting in inhibition of DNA synthesis and function with cytotoxic DNA strandbreaks. (medscape.com)
  • Jarmuła A. (2010) Antifolate inhibitors of thymidylate synthase as anticancer drugs. (guidetopharmacology.org)
  • Thymidylate synthase (TYMS) enhancer region genotype-directed phase II trial of oral capecitabine for 2nd line treatment of advanced pancreatic cancer. (cdc.gov)
  • Thymidylate synthase genotype-directed neoadjuvant chemoradiation for patients with rectal adenocarcinoma. (cdc.gov)
  • Thymidylate synthase gene copy number as a predictive marker for response to pemetrexed treatment of lung adenocarcinoma. (cdc.gov)
  • Fluorouracil inhibits thymidylate synthetase, the key enzyme involved in the biosynthesis of pyrimidine. (lekarstwo.ru)
  • TFD mono-phosphate also prevents the thymidylate synthetase enzyme reversibly, which is useful in DNA replication 4-6 . (ijpsr.com)
  • The possible relevance of the sulphur geometry in two of the compounds to certain structural aspects of the action of the enzyme thymidylate synthetase is also pointed out. (iisc.ac.in)
  • Capecitabine is a prodrug that is converted to fluorouracil following oral administration, which in turn inhibits thymidylate synthetase, blocking the m. (arogga.com)
  • Undergoes hydrolysis in liver and tissues to form the active moiety (fluorouracil), inhibiting thymidylate synthetase, which in turn blocks methylation of deoxyuridylic acid to thymidylic acid. (medscape.com)
  • Interferes with DNA synthesis by blocking methylation of deoxyuridylic acid, inhibiting thymidylate synthetase and subsequently cell proliferation. (medscape.com)
  • It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid. (ucdenver.edu)
  • Decreased expression of six RNA species was seen at various time points in all cell strains analyzed, these were: plasminogen activator (PLAT), centromere protein F (CPF), replication factor C (RFC3), thymidylate synthetase (TYMS), a putative mitotic checkpoint kinase (BUB1) and a gene of unknown function (GenBank accession number AI859865). (cdc.gov)
  • Calcium folinate enhances the inhibition of thymidine synthetase by increasing the intracellular folate pool, thus stabilizing the fluorouracil-thymidine synthetase complex and increasing its activity. (lekarstwo.ru)
  • Inhibition of thymidylate synthesis is probably the single most important consequence in the overall reaction scheme. (medquizzes.net)
  • Weekly subcutaneous injections of 1,2-dimethethyhydrazine into 6-week-old rats markedly increased thymidylate synthetase (TS) in the poorly differentiated, and thymidine kinase in the well-differentiated adenocarcinomas of the colon. (cancerprev.org)
  • 2011) Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria. (guidetopharmacology.org)
  • The influence of methylenetetrahydrofolate reductase and thymidylate synthetase gene polymorphisms on lung adenocarcinoma occurrence. (cdc.gov)
  • Resistance to 5-FU is a major clinical problem as mediated predominantly by over expression of Thymidylate Synthetase. (dcu.ie)
  • Binds to and stabilizes ternary complex of FdUTP (intracellular active metabolite of fluoropyrimidines) and thymidylate synthetase (TS), augmenting cytotoxic effects of 5-fluorouracil. (medscape.com)
  • It irreversibly binds to dihydrofolate reductase, inhibiting the formation of reduced folates, and thymidylate synthetase, resulting in inhibition of purine and thymidylic acid synthesis. (medicscientist.com)
  • Therefore, SAM deficiency speeds up the use of 5,10-MTHF for the MTHFR reaction but reduces its availability for the alternate thymidylate synthetase reaction, which normally regulates the nucleotide balance of deoxyuridine monophosphate (dUMP) and deoxythymidine monophosphate (dTMP). (campuscrosswalk.org)
  • Undergoes hydrolysis in liver and tissues to form the active moiety (fluorouracil), inhibiting thymidylate synthetase, which in turn blocks methylation of deoxyuridylic acid to thymidylic acid. (medscape.com)
  • A filter assay for thymidylate synthetase using 5-fluoro-2'-deoxyuridylate as an active site titrant. (colorado.edu)