Methotrexate acts by interfering with the normal intracellular metabolism of which of the following nutrients?

Methotrexate acts by interfering with the normal intracellular metabolism of which of the following nutrients?

• A. Thiamin
• B. Carnitine
• C. Folate
• D. Vitamin D

Answer: (C)

Methotrexate is an antifolate that blocks dihydrofolate reductase, stopping the regeneration of tetrahydrofolate and thereby disrupting folate-dependent one-carbon transfer reactions needed to make thymidine and purines. Without this folate-activated help, DNA synthesis in rapidly dividing cells falters, leading to impaired cell replication. Leucovorin rescue can provide a bypass to protect normal cells by supplying a usable form of folate. The other nutrients listed aren’t targeted by this mechanism, since thiamin, carnitine, and vitamin D pathways do not rely on dihydrofolate reductase–dependent folate metabolism.

Methotrexate is an antifolate that blocks dihydrofolate reductase, stopping the regeneration of tetrahydrofolate and thereby disrupting folate-dependent one-carbon transfer reactions needed to make thymidine and purines. Without this folate-activated help, DNA synthesis in rapidly dividing cells falters, leading to impaired cell replication. Leucovorin rescue can provide a bypass to protect normal cells by supplying a usable form of folate. The other nutrients listed aren’t targeted by this mechanism, since thiamin, carnitine, and vitamin D pathways do not rely on dihydrofolate reductase–dependent folate metabolism.