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).<br><br>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).
黄烷酮还原酶1和2(NQO1和NQO2)构成了哺乳动物黄烷酮还原酶酶家族,这些酶负责通过FAD介导的方式对黄烷酮底物进行还原反应。与使用NADPH作为辅底物的NQO1不同,NQO2采用一组罕见的氢供体,即N-甲基或N-核糖基烟酰胺(RFDHN)。NQO2以二聚体形式呈现活性,每个亚基结合一个FAD基团(Wu等人,1997年)。NQO2能够将某些黄烷酮底物转化为反应性更强的化合物,这些化合物能够导致细胞损伤(Celli等人,2006年,Knox等人,2000年)。
褪黑素(MLT)具有抗氧化作用,并能与NQO2结合,抑制其活性。NQO2的抑制可能导致细胞免受高度反应性物种产生的保护(Calamini等人,2008年)。白藜芦醇是一种存在于葡萄中,尤其在红葡萄酒中含量丰富的植物多酚。研究表明,白藜芦醇具有抗氧化和抗癌化学预防作用(Jang等人,1997年)。其存在于红葡萄酒中还被认为具有心脏保护作用,即所谓的“法国悖论”;在某些法国地区,心血管疾病的发病率较低,这些地区红葡萄酒和饱和脂肪的摄入量大于美国(Renaud与de Lorgeril,1992年,Bradamante等人,2004年)。白藜芦醇的最高亲和力靶点是NQO2。通过抑制NQO2,白藜芦醇可能保护细胞免受反应性中间体的侵害,并最终预防癌症(Buryanovskyy等人,2004年,St John等人,2013年)。
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