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

Enoyl-[acyl-carrier-protein] reductase, frequently referred to as InhA, is an essential enzyme in the Mycobacterium tuberculosis fatty acid synthase II (FAS-II) system (UniProt: P9WGR1). It catalyzes the NADH-dependent reduction of long-chain trans-2-enoyl-acyl carrier protein (ACP) fatty acids, which are precursors to mycolic acids (PubMed: 15615687). Mycolic acids are long-chain fatty acids that constitute a major and vital component of the mycobacterial cell wall, contributing to its low permeability and virulence (StatPearls: Isoniazid). InhA is the primary target of isoniazid, a cornerstone of tuberculosis treatment, as well as the second-line drugs ethionamide and prothionamide (PubChem: CID 3767). These drugs function as prodrugs that require activation by bacterial enzymes to form a covalent adduct with NAD+; this adduct then occupies the InhA active site, effectively halting cell wall synthesis and leading to bacterial lysis (PubMed: 15615687).

Other names

InhANADH-dependent enoyl-[acyl-carrier-protein] reductaseEnoyl-ACP reductase2-trans-enoyl-ACP reductaseNADH-dependent enoyl-ACP reductase

Inhibition of enoyl-ACP reductase activity through the formation of a covalent drug-NAD adduct (e.g., isonicotinyl-NAD), which competitively inhibits the enzyme and prevents the synthesis of mycolic acids required for the mycobacterial cell wall (PubMed: 15615687; StatPearls: Isoniazid).