Enoyl-[acyl-carrier-protein] reductase [NADH] (InhA)

Enoyl-[acyl-carrier-protein] reductase [NADH] (InhA) is a NADH-dependent enzyme found in *Mycobacterium tuberculosis* and is part of the type II fatty acid synthase (FAS-II) system. It catalyzes the reduction step in the elongation cycle of fatty acid synthesis, specifically the NADH-dependent reduction of long-chain trans-2-enoyl-acyl carrier proteins, which is essential for the production of mycolic acids—core components of the mycobacterial cell wall. InhA is a validated therapeutic target, being the primary target of the first-line tuberculosis drug isoniazid as well as related drugs like ethionamide. InhA inhibition results in defective mycolic acid biosynthesis, leading to impaired cell wall formation and bacterial death. Resistance to isoniazid is frequently due to mutations in the inhA gene or the KatG enzyme, highlighting the clinical importance of direct InhA inhibitors that bypass the need for pro-drug activation.

Other names

InhAEnoyl-ACP reductaseEnoyl-acyl carrier protein reductaseNADH-dependent enoyl-[acyl-carrier-protein] reductase

Competitive inhibition at the NADH-binding site - Formation of covalent adduct (e.g., INH-NAD) that inactivates the enzyme - Blockade of fatty acyl substrate binding pocket