How does methotrexate exert its therapeutic effect?

Methotrexate exerts its therapeutic effect primarily by inhibiting dihydrofolate reductase (DHFR). This enzyme plays a crucial role in the folate metabolic pathway, specifically in the reduction of dihydrofolate to tetrahydrofolate, which is essential for the synthesis of purines and thymidylate. By inhibiting DHFR, methotrexate effectively reduces the availability of folate derivatives necessary for the production of nucleic acids, thereby affecting DNA and RNA synthesis.

This mechanism is particularly important in rapidly dividing cells, such as those found in cancer or in certain autoimmune diseases. The diminished nucleotide synthesis leads to cytotoxic effects in cancer cells and can help modulate immune responses in conditions like rheumatoid arthritis and psoriasis.

Other options, such as transpeptidase inhibition or DNA gyrase inhibition, refer to different mechanisms of action relevant to other classes of drugs but do not pertain to the action of methotrexate. Transpeptidase inhibition is associated with antibiotics like penicillin, while DNA gyrase inhibition is relevant for certain fluoroquinolone antibiotics. The activation of autolytic enzymes typically describes bacterial cell wall breakdown processes rather than the action of methotrexate. Thus,