Role of Coenzyme Q in Regenerating Vitamin E

Kagan 9322598通过电子传递使泛醌还原，形成泛喹酚，它向维生素E的苯氧基自由基提供电子，从而使维生素再生，并保存其有限的供应。在缺乏维生素E(维生素E缺乏)的情况下，泛醌的氧化还原循环可能导致氧自由基的产生和膜的氧化损伤，这些都是泛醌的促氧化作用。我们认为，在维生素E存在的情况下，泛醌参与依赖电子传递的抗氧化功能，而在缺乏维生素E的情况下，参与促氧化剂的作用是这一提议的主题。目前的建议是进行一项有限的可行性研究，以确定在检测微体膜内维生素E的内源水平所产生的维生素E的苯氧基自由基时的灵敏度限度，以便对该假说进行批判性检验。通过使用伦敦大学最近投入使用的脉冲傅里叶变换ESR光谱仪，有望提高灵敏度和光谱分辨率。该仪器将被用来表征维生素E的苯氧基自由基，并为起草一份NSF资助一项旨在了解辅酶Q在膜中维生素E再生机制中的作用的新倡议的全面提案提供初步数据。维生素E和辅酶Q(泛醌)是细胞膜不可缺少的成分。在线粒体中，泛醌是能量产生机制中的关键元素。我们认为泛醌在线粒体和其他电子传递膜上还有额外的功能：它们通过与维生素E相互作用参与膜的抗氧化保护，维生素E是膜的主要脂溶抗氧化剂，保护膜免受氧化应激的伤害。泛醌通过电子传递还原，形成泛喹酚，可循环利用维生素E，从而保存其有限的供应。泛醌的这种抗氧化功能依赖于维生素E。此外，在缺乏维生素E的情况下(维生素E缺乏)，泛醌可能参与氧自由基的产生和膜的氧化损伤。我们认为，泛醌参与维生素E的循环是电子传递膜中泛醌抗氧化作用的主要机制。这项提案的主题是研究泛醌的这两种作用--在有维生素E的情况下作为电子传递依赖型抗氧化剂，在没有维生素E的情况下作为促氧化剂。***

Kagan 9322598 The reduction of ubiquinones by electron transport results in the formation of ubiquinols which donate electrons to phenoxyl radicals of vitamin E, thereby regenerating the vitamin and conserving its limited supply. In the absence of vitamin E (in vitamin E deficiency), redox-cycling of ubiquinones may result in the generation of oxygen radicals and oxidative damage of membranes; these are prooxidant effects of ubiquinones. We suggest that the involvement of ubiquinones: electron transport-dependent antioxidant function in the presence of vitamin E and prooxidant in the absence of vitamin E is the subject of this proposal. The present proposal is to undertake a limited feasibility study to determine the limits of sensitivity in detecting phenoxyl radicals of vitamin E generated from endogenous levels of the vitamin in microsomal membranes so that the hypothesis can be critically tested. An increase in sensitivity and spectral resolution is expected by using a pulsed Fourier transform ESR spectrometer recently commissioned at London University. The instrument will be used to characterize phenoxyl radicals of vitamin E and possibly ubisemiquinone radicals and provide preliminary data for use in drafting a fuyll proposal for NSF funding of a new initiative aimed to understand the role of coenzyme Q in mechanisms of vitamin E regeneration in membranes. %%% Vitamin E and Coenzyme Q (ubiquinones) are indispensible components of cellular membranes. In mitochondria, ubiquinones act as key elements in energy producing machinery. We suggest that ubiquinones have an additional function in mitochondria and other electron transport membranes: they are involved in membrane antioxidant protection by interacting with vitamin E. Vitamin E is the major lipid-soluble antioxidant of membranes which protects membranes against oxidative stress. The reduction of ubiquinones by electron transport results in the formation of ubiquinols which can recycle vitamin E thus conserving its limited supply. This antioxidant function of ubiquinones is vitamin E-dependent. Moreover, in the absence of vitamin E (in vitamin E deficiency), ubiquinones may be involved in the generation of oxygen radicals and oxidative damage of membranes. We suggest that the involvement of ubiquinones in vitamin E recycling is the major mechanism of the ubiquinone antioxidant action in electron transport membranes. An investigation of these two roles of ubiquinones - as an electron transport-dependent antioxidant in the presence of vitamin E and as a prooxidant in the absence of vitamin E - is the subject of this proposal. ***