Nohl H, Gille L, Staniek K
Institute of Pharmacology and Toxicology, Veterinary University of Vienna, Austria.
Mol Aspects Med. 1997;18 Suppl:S33-40. doi: 10.1016/s0098-2997(97)00020-4.
Ubiquinol (QH2, reduced coenzyme Q) is increasingly reported to exert antioxidant functions besides its implication in mitochondrial energy metabolism. On the other hand ubisemiquinones (SQ-.) of the respiratory chain are considered to account for the production of superoxide radicals as a byproduct of cellular respiration. Since the formation of potentially prooxidative ubisemiquinones can be expected to result from the antioxidant activity of ubiquinol, the evaluation whether or not QH2 exerts antioxidant activities depends on the fate of antioxidant-derived metabolites and the existence of a natural recycling system for oxidized QH2. We have recently shown that SQ increasingly undergo autoxidation when approaching the external more polar phase of the membrane. In contrast to mitochondria where the QH2/ SQ-./Q pools are dynamically kept in relatively stable relationships the fate of semi and fully oxidized QH2 is not at all clear in LDL particles where QH2 is suggested to exert important antioxidant functions. Therefore, the antioxidant-derived metabolites of QH2 in liposomes following lipid peroxidation were studied with respect to their localization in the bilayer and the possibility to recycle oxidized QH2 via dihydrolipoic acid (DHLA). The results revealed a considerable fraction of QH2 existing in the outer membrane section where protons from the aqueous phase have access to allow autoxidation. DHLA was found to recycle oxidized QH2 although due to slow partition equilibration the reduction velocity appears to be not sufficient for therapeutic application.
除了参与线粒体能量代谢外,越来越多的研究报道泛醇(QH2,还原型辅酶Q)具有抗氧化功能。另一方面,呼吸链中的泛半醌(SQ-·)被认为是细胞呼吸副产物超氧自由基产生的原因。由于可以预期潜在的促氧化泛半醌的形成是由泛醇的抗氧化活性导致的,因此评估QH2是否具有抗氧化活性取决于抗氧化剂衍生代谢物的命运以及氧化型QH2天然循环系统的存在。我们最近发现,当接近膜的外部更具极性的相时,SQ越来越容易发生自氧化。与线粒体中QH2/SQ-·/Q池动态保持相对稳定的关系不同,在低密度脂蛋白颗粒中,半氧化和全氧化型QH2的命运完全不清楚,而QH2在其中被认为具有重要的抗氧化功能。因此,研究了脂质过氧化后脂质体中QH2的抗氧化剂衍生代谢物在双层中的定位以及通过二氢硫辛酸(DHLA)回收氧化型QH2的可能性。结果显示,在外膜部分存在相当一部分QH2,水相中的质子可以进入该区域从而使其发生自氧化。尽管由于分配平衡缓慢,还原速度似乎不足以用于治疗应用,但发现DHLA可以回收氧化型QH2。