NAD(P)H:quinone oxidoreductase 1 (NQO1)

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic, FAD-dependent enzyme that catalyzes the two-electron reduction of a broad range of quinones and other compounds using NADH or NADPH as electron donors[1][2][3]. This reduction bypasses the formation of semiquinone intermediates, thereby protecting cells from reactive oxygen species (ROS) and quinone toxicity[2][3]. NQO1 functions as an obligate dimer and is induced by oxidative stress through Nrf2 response pathways; it is active in many tissues and is considered a key cytoprotective and detoxifying enzyme[1][2][3]. In addition to xenobiotic detoxification, NQO1 participates in regulating cellular redox state, stabilizing the tumor suppressor p53, and metabolizing compounds such as vitamin K and coenzyme Q10[1][2][3]. Clinically, NQO1 is implicated in cancer, neurodegeneration, and as a target for bioactivation of certain anticancer prodrugs[2][3]. It is inhibited by agents such as dicoumarol and has several known pharmacogenomically-relevant polymorphisms that affect its activity and drug response[2][3].

Other names

NADH:quinone oxidoreductase-1NAD(P)H dehydrogenase [quinone] 1DT-diaphorase

Competitive inhibition at NAD(P)H or FAD binding site (e.g., dicoumarol). Bioactivation of prodrugs via reduction (e.g., β-lapachone, CB1954). Protection against oxidative stress by reducing reactive quinones to less toxic forms.