Ribosyldihydronicotinamide dehydrogenase [quinone] 2 (NQO2) (NQO2)

Ribosyldihydronicotinamide dehydrogenase [quinone] 2 (NQO2) is a cytosolic flavoenzyme that plays a critical role in the cellular defense against oxidative stress by catalyzing the two-electron reduction of quinones and their derivatives [UniProt: P16083]. Unlike the closely related NQO1, NQO2 is unique in its requirement for dihydronicotinamide riboside (NRH) as a co-substrate rather than NADH or NADPH [PubMed: 10806335]. By facilitating a direct two-electron transfer, the enzyme prevents the generation of reactive semiquinone intermediates and subsequent reactive oxygen species (ROS), thereby maintaining redox homeostasis [PubMed: 15615689]. NQO2 has also been identified as the MT3 binding site for melatonin, suggesting it serves as a link between circadian rhythms and antioxidant protection [PubMed: 10806335]. In clinical research, NQO2 is investigated for its involvement in the progression of various cancers and neurodegenerative conditions like Parkinson's disease, where its metabolic activity can influence disease susceptibility [PubMed: 22433012]. The enzyme is a known target for dietary polyphenols such as resveratrol and quercetin, as well as certain antimalarial drugs, which can modulate its activity to achieve chemopreventive or therapeutic effects [PubChem: NQO2].

Other names

Quinone reductase 2QR2NRH:quinone oxidoreductase 2Melatonin receptor 3MT3NRH dehydrogenase [quinone] 2

NQO2 catalyzes the two-electron reduction of quinones to hydroquinones, specifically utilizing dihydronicotinamide riboside (NRH) as an electron donor [UniProt: P16083]. This mechanism prevents the formation of highly reactive semiquinone radicals that would otherwise result from one-electron reductions, thereby protecting the cell from oxidative stress and DNA damage [PubMed: 15615689]. Additionally, NQO2 acts as a high-affinity binding site for melatonin (MT3), where it may mediate antioxidant signaling pathways [PubMed: 10806335].