FUNCTIONAL ROLES OF UBIQUINONE IN YEAST AND HUMAN CELLS

描述：泛醌(辅酶Q)在线粒体和 质膜电子传输，越来越多的证据表明 泛醌/泛醌氧化还原对也可作为一种有效的脂类。 可溶性抗氧化剂系统。在后一种能力中，泛喹酚(辅酶 Qh2)可清除脂质过氧化自由基，这是一类氧化产物， 是破坏细胞膜、蛋白质和DNA的主要原因。 越来越多的证据表明，哺乳动物细胞中的氧化损伤 是癌症和与年龄相关的退行性疾病的主要原因之一， 低密度脂蛋白脂类的氧化修饰可能计划 在冠状动脉疾病的发病过程中起着重要作用。 泛醌/泛喹酚是唯一一种脂溶性抗氧化剂 由哺乳动物细胞合成。虽然膳食补充剂含有 泛醌可增加肝脏和脂蛋白中的泛喹酚水平 对于动物来说，它对其他组织中泛醌的水平几乎没有影响。 因此，它是从头合成，设定了人体水平的泛醌和 泛喹酚。令人惊讶的是，泛醌生物合成的酶学 还不清楚，真核基因与酶的关系也不是很清楚 已经建立了。 这项拟议研究的目标包括阐明该基因。 泛醌生物合成的酶关系及其表征 负责生产泛苯二酚的多肽成分。 该实验系统利用了8个互补组 酿酒酵母中的辅酶Q缺失突变体。 酵母coq突变体的可获得性为 两种植物辅酶Q基因及其产物的分离和鉴定 酵母和哺乳动物。泛醌中间体的合成类似物提供了 在分离和鉴定中既可作为标准的试剂 作为酶的体外测定的底物 活动。实验方法采用了化学和化学相结合的方法， 描述真核生物生物合成步骤的遗传学和生物化学 负责泛苯二酚的生产，以及调查 泛醌/泛喹酚作为抗氧化剂的功能。

DESCRIPTION: Ubiquinone (coenzyme Q) functions in both mitochondria and plasma membrane electron transport, and a growing body of evidence suggests that the ubiquinol/ubiquinone redox couple also functions as a potent, lipid soluble antioxidant system. In this latter capacity, ubiquinol (coenzyme QH2) may scavenge lipid peroxyl radicals, a class of oxidative products that represents a major cause of damage to cellular membranes, proteins, and DNA. There is a growing body of evidence that oxidative damage in mammalian cells is one of the major causes of cancer and age-related degenerative diseases, and that oxidative modifications of low density lipoprotein lipids may plan an important role in the initiation of coronary artery disease. Ubiquinone/ubiquinol is the only lipid soluble antioxidant that can be synthesized by mammalian cells. Although dietary supplementation with ubiquinone increases ubiquinol levels in the liver and lipoproteins of animals, it has little impact on the levels of ubiquinone in other tissues. Thus, it is de novo synthesis that sets the body level of ubiquinone and ubiquinol. It is surprising that the enzymology of ubiquinone biosynthesis is not understood, and the eukaryotic gene enzyme relationships have not been established. The goals of the proposed research include the elucidation of the gene enzyme relationships of ubiquinone biosynthesis, and the characterization of the polypeptide components responsible for the production of ubiquinone. The experimental system takes advantage of eight complementation groups of ubiquinone deficient (coq) mutants in the yeast Saccharomyces cerevisiae. The availability of the yeast coq mutants provides the basis for the isolation and characterization of the COQ genes and their products in both yeast and mammals. Synthetic analogs of ubiquinone intermediates provide reagents that serve both as standards in the isolation and characterization of ubiquinone intermediates, and as substrates for in vitro assays of enzyme activities. The experimental approach employs the combination of chemistry, genetics, and biochemistry to delineate the eukaryotic biosynthetic steps responsible for the production of ubiquinone, as well as to investigate the function of ubiquinone/ubiquinol as an antioxidant.