Isoniazid (INH) is a prodrug requiring mycobacterial activation. Which enzyme activates INH and what is the primary target of the activated form?

• A KatG (catalase-peroxidase) activates INH; activated form inhibits InhA (enoyl-ACP reductase) in mycolic acid synthesis ✓
• B BioA (adenylate cyclase) activates INH; activated form inhibits arabinogalactan synthesis
• C PncA (pyrazinamidase) activates INH; activated form acidifies phagolysosome
• D EmbB (arabinosyltransferase) activates INH; activated form disrupts cell wall arabinogalactan

Explanation

INH is oxidized by the mycobacterial enzyme KatG (catalase-peroxidase) to form an isonicotinoyl radical, which then reacts with NAD+ to form INH-NAD adduct; this adduct potently inhibits InhA (enoyl-ACP reductase), the enzyme required for mycolic acid biosynthesis in the type II fatty acid synthase pathway. KatG mutations are the most common mechanism of INH resistance. PncA activates pyrazinamide (option C).

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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