ENZYMIC REACTIONS OF MODEL PLASMA LIPOPROTEINS

血浆脂蛋白(LPs)在不同的 血管外隔室，用于使用或储存它们。高潮 密度脂蛋白(HDL)、极低密度脂蛋白(VLDL)和乳糜粒是 在血浆中由两种酶修饰。高密度脂蛋白的游离胆固醇是 卵磷脂：胆固醇酰基转移酶转化为酯化形式 (LCAT)，一种也具有磷脂酶A2活性的酶；这两个过程 被apoA-I激活。脂蛋白脂肪酶(LPL)可将 极低密度脂蛋白和乳糜粒的甘油三酯，这一反应是由 载脂蛋白C-II。这些酶在决定细菌的分布方面很重要。 不同脂类间的甾基或脂肪酰基及其分布 这些脂类在血浆脂蛋白中。该基因的分子描述 这两种酶的活性和特异性是一种 对脂类代谢的深入了解，因为这些活动决定了 产品结构，影响其在血浆中的分布。我们 建议a)将这些酶的特性分解成组分 这取决于个体的共价结构 底物分子或宏观性质，如流动性或 大小，b)测量LCAT的缔合自由能(Delta Ga)，以及 在磷脂存在和不存在其脱辅基蛋白的情况下的LPL 激活剂，以及c)确定Delta Ga和 底物和产物LP的结构。这些研究将是 用乙醚进行类脂，以及各种可水解物 荧光或放射性脂质。这项调查涉及到脂质 LPL和LCAT活性的合成、荧光和放射性分析 脂蛋白重组和平衡结合技术。首字母 研究将利用单个双层囊泡，然后继续 特征明确的模型和原生LP。因为生活方式决定了，在 第二部分，脂类的脂肪酸组成、数量和结构 在包含它们的有限合伙人中，我们的研究应该有助于我们理解 影响血浆脂蛋白周转率和脂代谢的因素 将军。

The plasma lipoproteins (LPs) transport lipids between various extravascular compartments where they are utilized or stored. The high density LPs (HDL), very low density LPs (VLDL), and chylomicrons are modified in plasma by two enzymes. The free cholesterol of HDL is converted to its esterified form by lecithin:cholesterol acyltransferase (LCAT), an enzyme that also has phospholipase A2 activity; both processes are activated by apoA-I. Lipoprotein lipase (LPL) hydrolyzes the triglycerides of VLDL and chylomicrons, a reaction that is timulated by apoC-II. These enzymes are important in determining the distribution of steryl or fatty acyl groups among individual lipids and the distribution of these lipids among the plasma LPs. A molecular description of the activities and specificities of both enzymes is a key component of a thorough understanding of lipid metabolism since these activities determine the product structure, which affects their distribution inplasma. We propose a) to resolve the specificities of these enzymes into components that are dependent either upon the covalent structure of the individual substrate molecules or upon macroscopic properties such as fluidity or size, b) to measure the free energy of association (Delta Ga) of LCAT and LPL with phospholipids in the presence and absence of their apoprotein activators, and c) to determine the relationship between Delta Ga and the structure of the substrate and product LPs. These studies will be conducted with ether analogs of lipids, and a variety of hydrolyzable fluorescent or radioactive lipids. This investigation involves lipid synthesis, fluorescence and radioactive assays of LPL and LCAT activity, lipoprotein reassembly, and equilibrium binding techniques. The initial studies will utilize single bilayer vesicles and then progress to well-characterized model and native LPs. Since lifestyles determine, in part, the fatty acid composition of lipids, and the quantity and structure of the LPs that contain them, our studies should aid in our understanding of the factors that affect plasma LP turnover and lipid metabolism in general.