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. ***
