Role of Coenzyme Q in Regenerating Vitamin E

辅酶 Q 在维生素 E 再生中的作用

• 批准号: 9322598
• 负责人: Valerian Kagan
• 金额: $ 5万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 1996-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9322598&HistoricalAwards=false
• 关键词: Role; Coenzyme; Regenerating; Vitamin

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. ***

通过电子传递还原泛醌导致泛醇的形成，泛醇将电子提供给维生素E的苯氧基自由基，从而再生维生素并保存其有限的供应。 在缺乏维生素E的情况下（维生素E缺乏症），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;这些是泛醌的促氧化作用。 我们建议，泛醌的参与：电子传递依赖的抗氧化功能的存在下，维生素E和促氧化剂的情况下，维生素E是本提案的主题。 目前的建议是进行一项有限的可行性研究，以确定检测微粒体膜中维生素E内源性水平产生的维生素E苯氧基自由基的灵敏度限度，以便对假设进行严格检验。 增加的灵敏度和光谱分辨率，预计使用脉冲傅里叶变换ESR光谱仪最近委托伦敦大学。 该仪器将用于表征维生素E的苯氧基自由基和可能的泛半醌自由基，并提供初步数据，用于起草一份由NSF资助的新倡议的fuyll提案，该倡议旨在了解辅酶Q在膜中维生素E再生机制中的作用。 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的关键元素。 我们认为，泛醌在线粒体和其他电子传递膜中具有额外的功能：它们通过与维生素E相互作用参与膜抗氧化保护。 维生素E是膜的主要脂溶性抗氧化剂，可保护膜免受氧化应激。 通过电子传递减少泛醌会导致泛醇的形成，泛醇可以回收维生素E，从而保护其有限的供应。 泛醌的这种抗氧化功能是维生素E依赖性的。 此外，在缺乏维生素E的情况下（维生素E缺乏症），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回收的电子传递膜中的泛醌抗氧化作用的主要机制。 这两个角色的泛醌的调查-作为电子传递依赖性的抗氧化剂在维生素E的存在下，作为一个prooxidant在维生素E的情况下-是这个建议的主题。 ***