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.
In normal cells – MTHF is a key component of cell division in healthy cells
The MTHF molecule interacts with two other molecules in a protein complex which, collectively, form one of the building blocks for DNA (Thymidine – dTMP) required for cell division (DNA synthesis) and the repair of damaged DNA.
In tumour cells – MTHF (arfolitixorin) interacts with 5-FU during chemotherapy, resulting in an enhanced anti-tumour effect
The objective is to stop the growth of tumours in a cancer patient. Treatment with the cytotoxin, 5-FU, blocks the metabolism to one of the DNA building blocks required for cell division (Thymidine – dTMP). Increasing the concentration of MTHF molecules, which is currently done with leucovorin, increases the efficacy of 5-FU and reduces the production of Thymidine. The result is that more tumour cells die because the cells are starved of new DNA building blocks. Normal cells divide much less often and are consequently not affected in the same way by this Thymidine starvation, and the side effects of 5-FU treatment are thus relatively mild. Arfolitixorin treatment, which has been shown to result in MTHF levels that are at least 3-4 times higher than in comparable treatment with leucovorin, consequently generates the preconditions for a substantial increase in the efficacy of 5-FU and, hence, of substantially more patients responding to treatment.