Department of Toxicology, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, Maastricht 6200 MD, The Netherlands.
Department of Human Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, P.O. Box 616, Maastricht 6200 MD, The Netherlands.
Int J Mol Sci. 2014 Apr 30;15(5):7475-84. doi: 10.3390/ijms15057475.
Antioxidants act as intermediates by picking up the high unselective reactivity of radicals and transferring it to other molecules. In this process the reactivity is reduced and becomes selective. This channeling of the reactivity can cause selective toxicity. The antioxidant quercetin is known to channel the reactivity towards thiol groups. The present study compares the thiol reactivity of quercetin with that of 4'O-methylquercetin (tamarixetin) towards creatine kinase (CK), a vital protein that contains a critical thiol moiety. Our results showed that oxidized quercetin and oxidized tamarixetin both adduct CK, which then loses its enzymatic function. Ascorbate, an important representative of the antioxidant network, is able to prevent adduction to and thus the inhibition of the enzyme by tamarixetin but not by quercetin. Apparently, tamarixetin is less thiol toxic than quercetin, because--rather than adduction to CK--tamarixetin quinone prefers to pass reactivity to the antioxidant network, i.e., to ascorbate. The findings exemplify that radical scavenging flavonoids pick up the reactivity of radicals and act as a pivot in directing the way the reactivity is channeled. A mere minor structural difference of only one methyl moiety between quercetin and tamarixetin appears to have a high impact on the selective, thiol toxicity.
抗氧化剂作为中间体，通过捕获自由基的高非选择性反应性并将其转移到其他分子上。在这个过程中，反应性降低并变得具有选择性。这种反应性的定向可以导致选择性毒性。已知抗氧化剂槲皮素可将反应性导向巯基基团。本研究比较了槲皮素和 4'O-甲基槲皮素（柽柳素）对肌酸激酶（CK）的巯基反应性，CK 是一种含有关键巯基部分的重要蛋白质。我们的结果表明，氧化的槲皮素和氧化的柽柳素都与 CK 加合物，然后失去其酶功能。抗坏血酸，抗氧化网络的重要代表，能够防止柽柳素而不是槲皮素与 CK 的加合物，从而抑制酶。显然，柽柳素比槲皮素的巯基毒性更小，因为柽柳素醌而不是与 CK 加合物，更喜欢将反应性传递到抗氧化网络，即抗坏血酸。这些发现例证表明，清除自由基的类黄酮吸收自由基的反应性，并作为引导反应性定向的枢轴。槲皮素和柽柳素之间仅相差一个甲基基团的微小结构差异，似乎对选择性、巯基毒性有很大影响。
