Isoniazid (INH) requires activation by the mycobacterial enzyme KatG (catalase-peroxidase). The active intermediate then inhibits which mycobacterial enzyme?
- A DNA gyrase, causing strand breaks
- B InhA (enoyl-ACP reductase), disrupting mycolic acid synthesis ✓
- C Dihydropteroate synthase, blocking folate synthesis
- D RNA polymerase, preventing mycobacterial transcription
Explanation
Isoniazid is a prodrug activated by KatG to form an isonicotinoyl-NAD adduct (isonicotinyl-NADH), which inhibits InhA—the enoyl-acyl carrier protein reductase that catalyses the final step in the fatty acid elongation cycle required for mycolic acid synthesis. Disruption of mycolic acid production destroys the mycobacterial cell wall, which is otherwise impermeable. Resistance most commonly arises from katG mutations (loss of activation) or inhA promoter mutations (overexpression of target). RNA polymerase is rifampicin's target; DNA gyrase is the fluoroquinolone target.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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