Nohl H, Gille L, Kozlov A V
Institute of Pharmacology and Toxicology, Veterinary University of Vienna, Austria.
Free Radic Biol Med. 1998 Oct;25(6):666-75. doi: 10.1016/s0891-5849(98)00105-1.
Ubiquinol (QH2) is increasingly used as antioxidant for the treatment of a variety of diseases and the modulation of biological aging; however, the biological significance of secondary reaction products has been disregarded so far. Our studies on the antioxidant activity of ubiquinol in peroxidizing lipid membranes demonstrate the existence of ubisemiquinone (SQ*) as the first reaction product of ubiquinol. A fraction of SQ* derived from the antioxidative activity of QH2 was detected in the outer section of the membrane bordering the aqueous phase. This localization allows an access of protons and water from the aqueous phase to SQ* a prerequisite earlier found to trigger autoxidation. Superoxide radicals emerging from this fraction of autoxidizing SQ* form H2O2 by spontaneous dismutation. SQ* not involved in autoxidation may react with H2O2. Transfer of the odd electron to H2O2 resulted in HO* and HO- formation by homolytic cleavage. An analogous reaction was also possible with lipid hydroperoxides which accumulate in biological membranes during lipid peroxidation. The reaction products emerging from this reaction were alkoxyl radicals. Both HO* and alkoxyl radicals are strong initiators and promoters of lipid peroxidation. Indirect evidence of the existence and prooxidative activities of these secondary reaction products came from comparative studies with vitamin E. While in the absence of other reactants, QH2 and vitamin E were equally effective in scavenging lipid radicals; the radical protecting activity of QH2 was found to be significantly lower as compared to vitamin E when these antioxidants operate in peroxidizing lipid membranes. This discrepancy reveals that the antioxidative activity of coenzyme Q is compulsorily linked to the formation of split products counteracting the membrane protective effect of this natural antioxidant.
泛醇（QH2）越来越多地被用作抗氧化剂，用于治疗多种疾病和调节生物衰老；然而，到目前为止，二级反应产物的生物学意义一直被忽视。我们对泛醇在过氧化脂质膜中的抗氧化活性的研究表明，半醌自由基（SQ*）作为泛醇的首个反应产物存在。在与水相接壤的膜外层检测到了一部分源自QH2抗氧化活性的SQ*。这种定位使得质子和水能够从水相进入SQ*，这是之前发现的引发自氧化的一个先决条件。这部分自氧化的SQ产生的超氧自由基通过自发歧化形成过氧化氢。未参与自氧化的SQ可能会与过氧化氢反应。奇数电子转移到过氧化氢上会通过均裂产生羟基自由基（HO*）和氢氧根离子（HO-）。脂质过氧化过程中在生物膜中积累的脂质氢过氧化物也可能发生类似反应。该反应产生的产物是烷氧基自由基。HO*和烷氧基自由基都是脂质过氧化的强引发剂和促进剂。这些二级反应产物的存在及其促氧化活性的间接证据来自与维生素E的比较研究。在没有其他反应物的情况下，QH2和维生素E在清除脂质自由基方面同样有效；然而，当这些抗氧化剂在过氧化脂质膜中起作用时，发现QH2的自由基保护活性明显低于维生素E。这种差异表明，辅酶Q的抗氧化活性必然与分裂产物的形成相关联，而这些分裂产物会抵消这种天然抗氧化剂对膜的保护作用。
