A patient receiving methotrexate for rheumatoid arthritis develops macrocytic anemia with hypersegmented neutrophils. The drug produces this picture by inhibiting which enzyme?
- A Thymidylate synthase
- B Dihydrofolate reductase ✓
- C Methionine synthase
- D Methylene tetrahydrofolate reductase
Correct answer: B. Dihydrofolate reductase
Explanation
Methotrexate is a structural analog of folic acid that competitively inhibits dihydrofolate reductase, blocking reduction of dihydrofolate to tetrahydrofolate. Without THF, thymidine and purine synthesis fail, producing megaloblastic changes identical to folate deficiency. Thymidylate synthase is inhibited by 5-fluorouracil, not methotrexate. Methionine synthase uses methylcobalamin and is blocked neither by methotrexate nor by trimethoprim, another antifolate acting on bacterial DHFR.
Reference: Lippincott's Illustrated Reviews: Biochemistry, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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