The activation of lipoprotein lipase by apolipoprotein C-II

载脂蛋白C-II对脂蛋白脂肪酶的激活

• 批准号: nhmrc : 251701
• 负责人: A/Pr Geoffrey Howlett
• 金额: $ 16.7万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/activation-lipoprotein-lipase-c-ii/82308
• 关键词: activation; lipoprotein; lipase; apolipoprotein; II

Abnormalities in blood lipid levels are common in our society. Treatment of these conditions adds a heavy burden to national health-care costs. Lipoprotein lipase is a plasma enzyme that plays a central role in maintaining safe blood lipid levels. The action of lipoprotein lipase in subjects on a western diet leads to the hydrolysis of about 150g of plasma triacylglycerol daily. Naturally occurring mutations in lipoprotein lipase, associated with a complete loss of enzyme activity, result in a high blood-lipids that can lead to premature atherosclerosis. Regulation of lipoprotein lipase occurs via an interaction with the regulatory protein apolipoprotein C-II. Individuals with apolipoprotein C-II deficiency also exhibit abnormal plasma lipid levels with an associated increased risk of coronary heart disease. These considerations demonstrate that the activation of lipoprotein lipase by apolipoprotein C-II is pivotal to the maintenance of normal blood lipid levels. The present proposal will establish the structure and orientation of apolipoprotein C-II in a lipid environment and provide a structural model for the activation of lipoprotein lipase by apolipoprotein C-II. These molecular details will serve as a model for the regulatory interactions of other apolipoproteins within lipoprotein particles and will generate leads for the development of new strategies for the treatment of blood lipid irregularities.

在我们的社会中，血脂水平异常是很普遍的。治疗这些疾病给国家保健费用增加了沉重负担。脂蛋白脂酶是一种血浆酶，在维持安全血脂水平中起着核心作用。在西方饮食的受试者中，脂蛋白脂肪酶的作用导致每天约150 g血浆三酰甘油的水解。脂蛋白脂肪酶的天然突变，与酶活性的完全丧失有关，导致高血脂，可导致过早的动脉粥样硬化。脂蛋白脂酶的调节通过与调节蛋白载脂蛋白C-II的相互作用发生。载脂蛋白C-II缺乏的个体也表现出异常的血浆脂质水平，与冠心病的风险增加相关。这些考虑表明，载脂蛋白C-II激活脂蛋白脂肪酶是维持正常血脂水平的关键。本研究将建立载脂蛋白C-II在脂质环境中的结构和取向，并为载脂蛋白C-II激活脂蛋白脂肪酶提供结构模型。这些分子的细节将作为一个模型的其他载脂蛋白内的脂蛋白颗粒的监管相互作用，并将产生线索的发展新的策略治疗血脂异常。