Isoniazid is activated by which bacterial enzyme?

• A. KasA.
• B. InhA.
• C. AhpC.
• D. KatG.

Answer: (D)

Isoniazid is a prodrug that must be activated by a mycobacterial enzyme to work. The enzyme that does this is KatG, a catalase-peroxidase. When KatG oxidizes isoniazid, it converts it into an active species that then forms an adduct with NAD+. This activated complex inhibits InhA, the enoyl-ACP reductase in the fatty acid synthase II pathway, which blocks synthesis of mycolic acids essential for the mycobacterial cell wall. Without proper mycolic acid production, the bacterium cannot maintain its cell wall and cannot replicate effectively. Other proteins listed aren’t responsible for activating isoniazid: InhA is the target inhibited after activation, KasA is another enzyme in the same biosynthetic pathway, and AhpC is a peroxide-detoxifying enzyme that may be upregulated in some resistance scenarios but does not activate the drug.