A 34-year-old man with HIV and CD4 count of 60 cells/mm3 presents with headache and CSF India ink positive for Cryptococcus neoformans. Induction therapy includes amphotericin B plus a second drug that acts by being converted to 5-fluorouracil within fungal cells. The enzyme responsible for this intracellular conversion is:

• A Cytosine deaminase ✓
• B Thymidylate synthase
• C Orotidine-5-phosphate decarboxylase
• D Dihydrofolate reductase

Explanation

Flucytosine enters fungal cells via cytosine permease and is deaminated to 5-fluorouracil by fungal cytosine deaminase, an enzyme absent in human cells, which explains its selectivity. 5-FU is then converted to 5-FUMP, inhibiting thymidylate synthase. Thymidylate synthase is the downstream target, not the converting enzyme, which kills option B.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.