HealthMap

Methotrexate and Dihydrofolate Reductase

• Yes, the primary mechanism of action of methotrexate is the potent inhibition of the enzyme dihydrofolate reductase (DHFR).
• Enzyme Blockade: By competitively binding to DHFR, methotrexate prevents the reduction of dihydrofolate to its active form, tetrahydrofolate.
• Metabolic Impact: This inhibition blocks the synthesis of purines and pyrimidines, which are essential building blocks for DNA and RNA synthesis.
• Clinical Implication: While this action helps reduce rapid cell proliferation in conditions like rheumatoid arthritis and certain cancers, it also significantly depletes active folate levels, often necessitating nutritional support to mitigate adverse effects.