NQO2:FAD dimer reduces quinones to hydroquinones

Stable Identifier
R-HSA-8936519
Type
Reaction [transition]
Species
Homo sapiens
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Quinone reductases 1 and 2 (NQO1 and NQO2) comprise the mammalian quinone reductase family of enzymes responsible for performing FAD-mediated reductions of quinone substrates. In contrast to NQO1, which uses NADPH as a co-substrate, NQO2 uses a rare group of hydride donors, N-methyl or N-ribosyl nicotinamide (RFDHN). NQO2 is active in dimeric form, binding one FAD group per subunit (Wu et al. 1997). NQO2 can transform certain quinone substrates into more highly reactive compounds capable of causing cellular damage (Celli et al. 2006, Knox et al. 2000).

Melatonin (MLT) has antioxidant effects and is able to bind NQO2, inhibiting its activity. Inhibition of NQO2 may lead to protection of cells against the production of highly reactive species (Calamini et al. 2008). Resveratrol is a phyto-polyphenol that is present in grapes and in significant amounts in grape juice and wines, particularly red wine. Resveratrol was found to be an anti-oxidant and a cancer chemopreventive agent (Jang et al. 1997). Its presence in red wine was also suggested to have cardioprotective effects, the so-called “French paradox”; an observation of lower incidence of cardiovascular disease in some French regions where red wine and saturated fats are consumed in greater quantities than in the US (Renaud & de Lorgeril 1992, Bradamante et al. 2004). The highest affinity target of resveratrol is NQO2. By inhibiting NQO2, resveratrol may protect cells against reactive intermediates and eventually cancer (Buryanovskyy et al. 2004, St John et al. 2013).

Literature References
PubMed ID Title Journal Year
10945627 Bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) by human NAD(P)H quinone oxidoreductase 2: a novel co-substrate-mediated antitumor prodrug therapy

Knox, RJ, Jenkins, TC, Hobbs, SM, Chen, S, Melton, RG, Burke, PJ

Cancer Res. 2000
16765324 NRH:quinone oxidoreductase 2 (NQO2) catalyzes metabolic activation of quinones and anti-tumor drugs

Celli, CM, Tran, N, Knox, R, Jaiswal, AK

Biochem. Pharmacol. 2006
8985016 Cancer chemopreventive activity of resveratrol, a natural product derived from grapes

Jang, M, Cai, L, Udeani, GO, Slowing, KV, Thomas, CF, Beecher, CW, Fong, HH, Farnsworth, NR, Kinghorn, AD, Mehta, RG, Moon, RC, Pezzuto, JM

Science 1997
9367528 Catalytic properties of NAD(P)H:quinone oxidoreductase-2 (NQO2), a dihydronicotinamide riboside dependent oxidoreductase

Wu, K, Knox, R, Sun, XZ, Joseph, P, Jaiswal, AK, Zhang, D, Deng, PS, Chen, S

Arch. Biochem. Biophys. 1997
1351198 Wine, alcohol, platelets, and the French paradox for coronary heart disease

Renaud, S, de Lorgeril, M

Lancet 1992
23953689 Design, synthesis, biological and structural evaluation of functionalized resveratrol analogues as inhibitors of quinone reductase 2

St John, SE, Jensen, KC, Kang, S, Chen, Y, Calamini, B, Mesecar, AD, Lipton, MA

Bioorg. Med. Chem. 2013
15350128 Crystal structure of quinone reductase 2 in complex with resveratrol

Buryanovskyy, L, Fu, Y, Boyd, M, Ma, Y, Hsieh, TC, Wu, JM, Zhang, Z

Biochemistry 2004
15492766 Cardiovascular protective effects of resveratrol

Bradamante, S, Barenghi, L, Villa, A

Cardiovasc Drug Rev 2004
18254726 Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2

Calamini, B, Santarsiero, BD, Boutin, JA, Mesecar, AD

Biochem. J. 2008
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Catalyst Activity
Title
dihydronicotinamide riboside quinone reductase activity of NQO2:FAD dimer [cytosol]
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