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THE MECHANISM OF ACTION
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IN NORMAL CELLS
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- DNA synthesis is vital for cells to be in good health.
- One key component for DNA synthesis is continuous access to DNA building blocks. To enable production of building blocks (5-dTMPÂ in particular), a ternary complex needs to be formed.
- To convert 5-dUMP to 5-dTMP, a ternary complex with together with the active ingredient of arfolitixorin – and a thymidylate synthase enzyme needs to be formed.
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Folic acid is converted by the human body into a pool of at least six interconvertible forms of reduced folates. Among the various metabolites involved, the active ingredient contained in arfolitixorin plays the most crucial role as the last reduced folate in the chain, which function as substrate for the TS enzyme. In the DNA synthesis, a complex is formed between the substrate and the TS enzyme to convert 5-dUMP to the DNA building block 5-dTMP. If the complex does not work, the formation of DNA is hindered which in turn inhibits cell growth. For this reason, TS is used as an important target for cancer chemotherapy to kill tumour cells.
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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 concentrations of the active metabolite 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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Last updated 02-01-2019
