High-Density Lipoprotein Species--Structures and Roles

描述(由申请人提供)：本项目旨在了解 高密度脂蛋白的天然分子形态，功能性 单个高密度脂蛋白物种的作用以及它们产生的过程 并被分解了。它还包括对突变和 与高密度脂蛋白代谢有关的关键基因的多态性 高密度脂蛋白物种形成的基因组决定因素及其遗传基础的鉴定 缺乏症。 具体目标： 1)完成隔离和 人高密度脂蛋白天然分子物种的选择表征 亲和免疫吸附。组成蛋白质和脂肪的化学计量学 在这些物种中将通过免疫化学方法和质量 光谱分析。 2)继续从人类高密度脂蛋白中分离新的蛋白质 并阐明它们的基因结构。候选蛋白质是由质量学发现的蛋白质 序列数据库中没有的光谱分析。 3)鉴定作为SR-Bl-HIVE底物和产物的高密度脂蛋白物种 脂肪酶(HL)、磷脂转移蛋白(PLTP)和 反应。 4)开发个体高密度脂蛋白的定量测量方法 血浆中的物种。 5)研究血浆高密度脂蛋白的组成和分布 高密度脂蛋白缺乏受试者的种类。 6)探讨HL、PLTP、SR-BI、ABCA1转运蛋白和载脂蛋白L基因突变和多态性对个体高密度脂蛋白分子物种代谢的影响。

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.