NQO1

NAD(P)H quinone dehydrogenase 1 (NQO1) is a cytosolic flavoprotein encoded by the NQO1 gene on chromosome 16q22.1. The enzyme forms a homodimer and uses FAD as a cofactor to catalyze the two-electron reduction of quinones and other redox-active compounds to hydroquinones, utilizing NADH or NADPH as electron donors. This two-electron pathway helps prevent the formation of semiquinone radicals and reactive oxygen species.

NQO1 participates in cellular defense against oxidative stress and the detoxification of quinones produced by metabolism or environmental exposures. In addition to detoxification, NQO1 can influence the stability of certain proteins, including p53, by binding and protecting it from proteasomal degradation. Expression of NQO1 is inducible by oxidative stress through the Nrf2-ARE pathway and is enriched in tissues such as liver, colon, and lung.

Genetic variation in NQO1 is well documented. The common 609C>T polymorphism (resulting in a Pro187Ser substitution) markedly reduces enzyme activity and stability in individuals homozygous for the T allele. Allele frequencies vary across populations. This polymorphism can influence an individual’s capacity to detoxify quinones and may modulate cancer risk and response to certain chemotherapy regimens.

Clinically, NQO1 activity affects the efficacy and toxicity of quinone-containing chemotherapeutic agents and may serve as a biomarker of oxidative stress and drug response in research and, to some extent, clinical settings. Inhibitors (e.g., dicoumarol) and inducers (e.g., oltipraz, sulforaphane) of NQO1 are used to explore its role in detoxification and redox biology.