The mechanism of action of MTHF when administered in combination with 5-fluorouracil

  • 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

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.

Last updated 09-08-2016