Methotrexate inhibits dihydrofolate reductase, leading to depletion of thymidine and purine synthesis. This action disrupts production of which type of biomolecules?

• A. Proteins
• B. Nucleotides
• C. Lipids
• D. Carbohydrates

Answer: (B)

Folate metabolism provides one-carbon units needed to build nucleotides, the building blocks of DNA and RNA. When methotrexate inhibits dihydrofolate reductase, tetrahydrofolate pools drop, cutting off the supply of 5,10-methylene-THF for thymidylate synthesis and folate derivatives needed for purine ring formation. This directly depletes thymidine and purine nucleotides, so the production of nucleotides is impaired. Without enough nucleotides, cells can’t adequately replicate DNA or transcribe RNA, which is why this drug effectively halts cell division. Proteins, lipids, and carbohydrates aren’t the primary targets of this folate-blocking mechanism, so they’re not the biomolecule groups most directly disrupted here.