American Board of Surgery Qualifying Exam (ABS QE) Practice Test

5-FU functions by inhibiting which of the following enzymes?

1. Dihydrofolate reductase

2. Thymidylate synthase

3. DNA polymerase

4. RNA polymerase

The correct answer is: Thymidylate synthase

5-Fluorouracil (5-FU) is a chemotherapeutic agent that primarily functions by inhibiting thymidylate synthase, an enzyme critical for DNA synthesis. Thymidylate synthase catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), which is essential for DNA replication and repair. By inhibiting this enzyme, 5-FU effectively disrupts the synthesis of thymidine, leading to a decrease in DNA production and ultimately resulting in cell cycle arrest and apoptosis in rapidly dividing cancer cells. The other enzymes mentioned are not inhibited by 5-FU. Dihydrofolate reductase is targeted by drugs like methotrexate, while DNA polymerase is involved in DNA replication and is not directly affected by 5-FU. RNA polymerase, responsible for synthesizing RNA, does not play a direct role in the mechanism of action of 5-FU, which is primarily focused on DNA synthesis interruption.