What is the primary mechanism of action of Isoniazid?

• A. Inhibits mycolic acid synthesis
• B. Inhibits nucleic acid synthesis
• C. Inhibits arabinosyl transferase
• D. Inhibits folic acid synthesis

Answer: (A)

The main concept here is that isoniazid works by blocking the production of mycolic acids, which are essential long-chain fatty acids in the cell wall of mycobacteria. It acts as a prodrug that is activated by the mycobacterial enzyme KatG. Once activated, it interferes with the fatty acid synthase II system, inhibiting the enzyme InhA and the synthesis of mycolic acids. Without these fatty acids, the mycobacterial cell wall cannot form properly, so the bacterium cannot maintain its structure and dies, particularly when it’s actively growing.

This mechanism is distinct from others listed: inhibiting nucleic acid synthesis is more characteristic of drugs like rifamycins or fluoroquinolones; inhibiting arabinosyl transferase is how ethambutol works, affecting arabinogalactan incorporation into the wall; and inhibiting folic acid synthesis is the action of drugs like sulfonamides or PAS. Isoniazid’s targeted disruption of mycolic acid synthesis explains its specific activity against mycobacteria.