High-Density Lipoprotein Species--Structures and Roles

描述（申请人提供）：本项目旨在了解 高密度脂蛋白的天然分子形态， 单个HDL种类的作用，以及它们产生的过程 被分解代谢它还包括研究突变的影响， 参与HDL代谢的关键基因的多态性， 确定HDL形态形成的基因组决定因素和HDL的遗传基础 缺乏症 具体目标： 1)为了完成隔离， 使用选择的人HDL的天然分子种类的表征 亲和免疫吸附组成蛋白质和脂类的化学计量 将通过免疫化学方法和质量 光谱分析 2)继续从人类HDL中分离新的蛋白质 并阐明它们的基因结构。候选者是通过大量发现的蛋白质 序列数据库中不存在的光谱分析。 3)为了表征作为SR-B1的底物和产物的HDL物质， 脂酶（HL）、磷脂转移蛋白（PLTP）和 反应. 4)开发个体HDL的定量测量方法 血浆中的物种 5)研究血浆高密度脂蛋白（HDL）的组成和分布 高密度脂蛋白缺乏的受试者。 6)确定HL、PLTP、SR-BI、ABCA 1转运蛋白和载脂蛋白L基因突变和多态性对HDL单个分子种类代谢的影响。

DESCRIPTION (Provided by applicant): This project is directed at understanding the native molecular speciation of high density lipoproteins, the functional roles of individual HDL species, and the processes by which they are generated and catabolized. It also includes study of the influence of mutations and polymorphisms in key genes involved in HDL metabolism with the objective of identifying genomic determinants of HDL speciation and the genetic basis of HDL deficiency disorders. Specific Aims: 1) To complete the isolation and characterization of the native molecular species of human HDL using selected affinity immunosorption. The stoichiometry of constituent proteins and lipids in those species will be established by immunochemical methods and mass spectroscopic analysis. 2) To continue to isolate novel proteins from human HDL and elucidate their gene structures. Candidates are proteins discovered by mass spectroscopic analysis that are not present in sequence databases. 3) To characterize the HDL species that are substrates and products of SR-Bl, -hepatic lipase (HL), -phospholipid transfer protein (PLTP), and - mediated reactions. 4) To develop methods for quantitative measurement of individual HDL species in plasma. 5) To study the composition and distribution of plasma HDL species of HDL deficient subjects. 6) To determine the impact of mutations andpolymorphisms in the HL, PLTP, SR-BI, the ABCA1 transporter, and apolipoprotein L genes on the metabolism of individual molecular species of HDL.