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The mechanism of action of MTHF when administered in combination with 5-fluorouracil
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- 5-dTMP is necessary for DNA synthesis
- The ternary complex is necessary to form 5-dTMP
- Increasing the concentration of MTHF stabilizes the ternary complex strengthening and prolonging the cytotoxic effect of 5-FU by blocking the DNA synthesis (primarily in cancer cells) – Cell death
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Intracellular reduced folates exist as a pool of at least six interconvertible forms. One of them, MTHF, is the essential one-carbon donor and reduced folate substrate for the enzyme TS. TS catalyzes the dUMP to deoxythymidine-5-dTMP. This enzymatic pathway is critical as it provides one of the four necessary nucleotide substrates for DNA synthesis. For this reason, TS has been an important target for cancer chemotherapy.
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Last updated 09-08-2016
