Reactome | NQO2:FAD dimer reduces quinones to hydroquinones

NQO2:FAD dimer reduces quinones to hydroquinones

Stable Identifier

R-HSA-8936519

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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NQO2:FAD dimer reduces quinones to hydroquinones

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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
16765324	NRH:quinone oxidoreductase 2 (NQO2) catalyzes metabolic activation of quinones and anti-tumor drugs Knox, R, Tran, N, Jaiswal, AK, Celli, CM	Biochem. Pharmacol.	2006
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, Chen, S, Melton, RG, Burke, PJ, Jenkins, TC, Hobbs, SM	Cancer Res.	2000
8985016	Cancer chemopreventive activity of resveratrol, a natural product derived from grapes Mehta, RG, Beecher, CW, Moon, RC, Fong, HH, Thomas, CF, Pezzuto, JM, Udeani, GO, Jang, M, Farnsworth, NR, Slowing, KV, Cai, L, Kinghorn, AD	Science	1997
9367528	Catalytic properties of NAD(P)H:quinone oxidoreductase-2 (NQO2), a dihydronicotinamide riboside dependent oxidoreductase Joseph, P, Sun, XZ, Chen, S, Deng, PS, Wu, K, Jaiswal, AK, Knox, R, Zhang, D	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 Calamini, B, Lipton, MA, Chen, Y, Jensen, KC, Kang, S, St John, SE, Mesecar, AD	Bioorg. Med. Chem.	2013
15350128	Crystal structure of quinone reductase 2 in complex with resveratrol Buryanovskyy, L, Zhang, Z, Wu, JM, Ma, Y, Hsieh, TC, Fu, Y, Boyd, M	Biochemistry	2004
15492766	Cardiovascular protective effects of resveratrol Villa, A, Bradamante, S, Barenghi, L	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