Regioselectivity and reversibility of the glutathione conjugation of quercetin quinone methide
Regioselectivity and reversibility of the glutathione conjugation of quercetin quinone methide
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DOI：
10.1021/tx990161k
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发表时间：
2000-03-01
影响因子：
4.1
通讯作者：
Rietjens, IMCM
中科院分区：
文献类型：
--
作者：
Boersma, MG;Vervoort, J;Rietjens, IMCM
研究了槲皮素邻醌的化学反应性、异构化和谷胱甘肽缀合。酪氨酸酶用于产生不稳定的槲皮素邻醌衍生物，可以在其随后被谷胱甘肽清除时观察到。产物的鉴定揭示了6-谷胱甘肽-槲皮素和8-谷胱甘肽-槲皮素加合物的形成。因此，特别是在槲皮素的A环中形成了谷胱甘肽加合物，这是先验没有预料到的结果。量子力学计算支持这样一种可能性，即这些谷胱甘肽加合物的形成可以通过槲皮素邻醌异构化为对醌甲基化物来解释。令人惊讶的是，这项研究的其他实验揭示了加合物的形成是可逆的，导致两种槲皮素谷胱甘肽加合物之间的相互转化，以及槲皮素醌甲基化物在不同于其产生的细胞位点上释放和进一步亲电子反应的可能性。
The chemical reactivity, isomerization, and glutathione conjugation of quercetin o-quinone were investigated. Tyrosinase was used to generate the unstable quercetin o-quinone derivative which could be observed upon its subsequent scavenging by glutathione. Identification of the products revealed formation of 6-glutathionyl-quercetin and 8-glutathionyl-quercetin adducts. Thus, in particular, glutathione adducts in the A ring of quercetin were formed, a result which was not expected a priori. Quantum mechanical calculations support the possibility that the formation of these glutathione adducts can be explained by an isomerization of quercetin o-quinone to p-quinone methides. Surprisingly, additional experiments of this study reveal the adduct formation to be reversible, leading to interconversion between the two quercetin glutathione adducts and possibilities for release and further electrophilic reactions of the quercetin quinone methide at cellular sites different from those of its generation.