The effects of methotrexate are not specific for cancer/neoplastic cells, and si

Question

The effects of methotrexate are not specific for cancer/neoplastic cells, and side effects of the drug are often experienced. These side effects include hair loss and low blood cell counts which are a result of methotrexate’s effect on processes with rapidly dividing cells. To alleviate some of the side effects, patients will often be given a dose of folinic acid. Folinic acid is a formyl derivative of tetrahydrofolic acid that can be used by normal cells without the action of dihydrofolate reductase. How does this folinic acid “rescue” act to alleviate/reduce the side effects?

Explanation / Answer

Methotrexate (MTX) blocks the enzyme di-hydro-folate reductase (DHFR) in our body. As a result, DNA synthesis is affected. Folinic acid does not require this enzyme; it can work in absence of DHFR also.

Folinic acid is a formyl derivative of “Tetra-hydro-folic acid”. It helps in de novo purine and pyrimidine synthesis. Now, during MTX treatment DHFR is not formed in our body; so purine and pyrimidine synthesis is hampered. Supplementation with “folinic acid” during methotrexate treatment will result in formation of tetra-hydro-folic acid even in absence of DHFR enzyme; so, no affect will be observed on purine and pyrimidine synthesis.

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