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

Enoyl-[acyl-carrier-protein] reductase [NADH] (commonly known as InhA) is an NADH-dependent enzyme in Mycobacterium tuberculosis that catalyzes the reduction step of fatty acid elongation in the type II fatty acid synthase (FAS-II) pathway, which is essential for the biosynthesis of mycolic acids, key components of the mycobacterial cell wall[8][4][2]. InhA is a validated therapeutic target for tuberculosis and is the primary molecular target of the frontline anti-tubercular drug isoniazid, as well as ethionamide and other experimental inhibitors[1][3][7]. Isoniazid is a prodrug that, once activated by KatG, forms an adduct with NADH to irreversibly inhibit InhA[3][5]. Mutations in inhA or its regulatory regions confer resistance to isoniazid and ethionamide and are a major cause of multidrug-resistant tuberculosis[9]. Direct InhA inhibitors not requiring prodrug activation are under clinical and preclinical development to address resistance and improve therapy for drug-sensitive and drug-resistant tuberculosis[1][7].

Other names

Enoyl-ACP reductaseInhAEnoyl-acyl carrier protein reductase InhANADH-dependent enoyl-acyl carrier protein reductase

Competitive inhibition of fatty acid synthesis by formation of inhibitory adducts (e.g., isoniazid-NAD) and occupation of the substrate or cofactor binding site\n- Inhibition of mycolic acid biosynthesis, leading to impaired cell wall formation and bacterial death[1][3][7][9]