Nitric oxide synthase 2 (inducible) (iNOS)

Nitric oxide synthase 2 (iNOS) is an inducible enzyme that catalyzes the synthesis of nitric oxide (NO) from L-arginine, oxygen, and NADPH [1]. Unlike the constitutive isoforms (nNOS and eNOS), iNOS expression is primarily regulated at the transcriptional level and is triggered by pro-inflammatory stimuli such as lipopolysaccharide (LPS) and cytokines like IFN-gamma or TNF-alpha [2]. Once expressed, iNOS produces significantly higher concentrations of NO for extended periods, which plays a critical role in the innate immune response by acting as a cytotoxic agent against bacteria, parasites, and tumor cells [3]. However, dysregulated or chronic overproduction of NO via the iNOS pathway is implicated in the pathogenesis of various inflammatory and autoimmune diseases, including septic shock, rheumatoid arthritis, and asthma [2,4]. Consequently, iNOS is a major therapeutic target, with drug development focusing on highly selective inhibitors that can mitigate inflammatory damage while sparing the physiological functions of constitutive NOS isoforms [1,3]. Citations: [1] UniProt Consortium, P35228 (NOS2_HUMAN); [2] Cinelli, M. A., et al. (2020) Medicinal Research Reviews, 'Inducible nitric oxide synthase: Regulation, structure, and inhibition'; [3] National Center for Biotechnology Information, Gene ID: 4843; [4] StatPearls, 'Physiology, Nitric Oxide'.

Other names

NOS2NOS-IIInducible nitric oxide synthaseHepatocyte NOSHEP-NOSiNOS / LPS-induced NO production pathway

Competitive inhibition of the L-arginine binding site, interference with the binding of the essential cofactor tetrahydrobiopterin (BH4), or transcriptional repression of the NOS2 gene to prevent enzyme induction.