NQO1
Description
The NQO1 (NAD(P)H quinone dehydrogenase 1) is a protein-coding gene located on chromosome 16.
NQO1, also known as NAD(P)H dehydrogenase [quinone] 1, is an enzyme encoded by the NQO1 gene in humans. This gene belongs to the NAD(P)H dehydrogenase (quinone) family and encodes a 2-electron reductase (enzyme). The protein encoded by this gene is an FAD-binding protein that forms homodimers and carries out the two-electron reduction of quinones to hydroquinones and other redox dyes. It prefers short-chain acceptor quinones like ubiquinone, benzoquinone, juglone, and duroquinone. The gene has an important paralog, NQO2. This protein resides in the cytosol. NQO1 enzyme expression is inducible by dioxin and can be inhibited by dicoumarol. NQO1 is a cytoplasmic enzyme that reduces quinones to hydroquinones, facilitating the two-electron reduction of quinone to hydroquinone.
NQO1 is a flavin-containing quinone reductase that catalyzes the two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors. This process occurs through a ping-pong kinetic mechanism where electrons are sequentially transferred from NAD(P)H to the flavin cofactor and then from reduced flavin to the quinone, bypassing the formation of semiquinone and reactive oxygen species. NQO1 plays a crucial role in regulating the cellular redox state primarily through quinone detoxification. It reduces components of the plasma membrane redox system, such as coenzyme Q and vitamin quinones, producing antioxidant hydroquinone forms. In this process, it may function as a superoxide scavenger to prevent hydroquinone oxidation and facilitate excretion. Conversely, NQO1 can activate quinones and their derivatives by generating redox reactive hydroquinones with DNA cross-linking antitumor potential. NQO1 acts as a gatekeeper of the core 20S proteasome, which is known to degrade proteins with unstructured regions. Upon oxidative stress, NQO1 interacts with tumor suppressors TP53 and TP73 in a NADH-dependent manner and inhibits their ubiquitin-independent degradation by the 20S proteasome.
NQO1 is also known as DHQU, DIA4, DTD, NMOR1, NMORI, QR1.
