A patient with acute myeloid leukemia is started on methotrexate. This drug inhibits dihydrofolate reductase (DHFR). Which biochemical consequence directly results from this inhibition?
- A Impaired methionine synthase reaction
- B Impaired methylmalonyl-CoA mutase activity
- C Impaired conversion of dihydrofolate to tetrahydrofolate ✓
- D Impaired gamma-carboxylation of glutamate residues
Correct answer: C. Impaired conversion of dihydrofolate to tetrahydrofolate
Explanation
Methotrexate is a structural analog of folate that competitively inhibits DHFR, blocking regeneration of tetrahydrofolate (THF) from dihydrofolate. This depletes one-carbon-carrying THF derivatives needed for thymidylate and purine synthesis, halting DNA synthesis. Impaired methionine synthase occurs in C12 deficiency. Methylmalonyl-CoA mutase requires adenosylcobalamin. Gamma-carboxylation requires vitamin K.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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