PRENOLS AND OTHER LIPIDS

异戊烯醇和其他脂质

• 批准号: 8130688
• 负责人: Christian R Raetz
• 金额: $ 46.51万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8130688
• 关键词: Acetates; Anabolism; Area; Arts; Atherosclerosis; Biological Models; Brain; Cardiolipins; Categories; Chemistry; Cholesterol; Complex; Cytoplasmic Granules; Data Analyses; Detection; Diabetes Mellitus; Disease; Disease model; Drug usage; Ensure; Escherichia coli; Family; Fingerprint; Genes; Genetic; Goals; Grant; Inflammation; Insulin; Knowledge; Label; Lipids; Lysine; Maps; Mass Spectrum Analysis; Measurement; Metabolic; Metabolism; Methods; Minor; Mus; Mutant Strains Mice; Online Systems; Pathway interactions; Pharmaceutical Preparations; Phosphatidylserines; Plasma; Process; Protocols documentation; Recycling; Rest; Source; Spectrometry, Mass, Electrospray Ionization; Structure; Testing; Tissues; Work; Yeasts; base; dolichoic acid; improved; lipid biosynthesis; lipid metabolism; macrophage; mevalonate; neuromelanin; novel; prenol; programs; stable isotope; therapeutic evaluation

The goal of Core K (Prenols and Other Lipids) is to provide comprehensive approaches to the isolation and identification of diverse prenols, cardiolipins and novel minor lipids in mouse macrophages and related sources under basal, stimulated or drug-treated conditions. The strategy will involve the quantification of known lipids, and the purification and structural characterization of novel minor lipids by state of the art ESI mass spectrometry and other structural methods. Core K will collaborate with other cores of the Consortium as they encounter new lipids in need of identification. Core K will work with the Chemistry Focus Area to ensure that novel structural proposals are validated by synthesis in a timely manner. In the coming grant period, Core K has the following specific aims, which are fully integrated with the rest of the Consortium: Specific Aim 1. Employ lipidomics to advance mechanistic understanding of metabolism, especially as it relates to prenols, cardiolipins and novel minor lipids. In addition to the Consortium-related aims, several hypothesis-driven approaches are described for elucidating the biosynthesis and function the A/-acyl-phosphatidylserines, a novel family of lipids discovered during the last grant period. Specific Aim 2: Employ lipidomics to investigate macrophages and tissues under pathological conditions as disease models, with emphasis on prenols, cardiolipins and novel minor lipids. In addition to the Consortium-related aims, hypothesis-driven approaches are described for elucidating the biosynthesis and function of the dolichoic acids, new prenols discovered in brain neuromelanin granules. Specific Aim 3: Develop lipid networks and maps from lipidomics data analysis, with a focus on prenols, cardiolipins and novel minor lipids. In addition to the Consortium-related aims, Core K will provide annotated pathways for lipid categories in model systems, like E. coli and yeast, which are not the focus of LIPID MAPS, but which are invaluable for uncovering new mechanisms of lipid biosynthesis and genetics. A comprehensive knowledge of the structure and function of lipids is crucial for understanding the mechanisms of important disease processes, such as atherosclerosis, inflammation and diabetes. The quantitative measurement of lipid levels enabled by mass spectrometry also facilitates the evaluation of the therapeutic actions of commonly used drugs, such as the cholesterol lowering or insulin sensitizing agents.

核心K（蛋白酶和其他脂质）的目标是为隔离提供全面的方法 并鉴定小鼠巨噬细胞中各种蛋白质醇，心磷脂和新型小脂质的鉴定以及相关的 基础，刺激或药物处理的条件下的来源。该策略将涉及量化 已知的脂质，以及新颖的小脂质的纯化和结构表征，通过艺术状态 质谱和其他结构方法。核心K将与财团的其他核心合作 当它们遇到需要识别的新脂质时。核心K将与化学重点区域合作 确保及时通过合成来验证新颖的结构建议。在即将到来的赠款中 时期，核心K具有以下特定目标，这些目标与财团的其余部分完全集成： 具体目的1。采用脂肪组学来提高对新陈代谢的机械理解， 尤其是与蛋白酶，心磷脂和新型小脂质有关。 除了联盟相关的目的外，还描述了几种假设驱动的方法 阐明生物合成和功能A/-Acyl-磷脂酰酶，这是一种新型的脂质家族 在最后一个赠款期间。 特定目的2：采用脂肪委员会在病理下研究巨噬细胞和组织 作为疾病模型的疾病，重点是蛋白酶，心磷脂和新型小脂质。 除了财团相关的目的外，还描述了与假设驱动的方法阐明 多甲酸的生物合成和功能，在脑神经元素颗粒中发现的新蛋白酶。 特定目的3：从脂质组学数据分析中开发脂质网络和地图，重点 前醇，心磷脂和新型小脂质。 除了与财团相关的目标外，核心K还将为脂质类别提供带注释的途径 模型系统，例如大肠杆菌和酵母菌，不是脂质图的重点，但对于它们来说是无价的 发现脂质生物合成和遗传学的新机制。 对脂质的结构和功能的全面了解对于理解 重要疾病过程的机制，例如动脉粥样硬化，炎症和糖尿病。这 质谱法实现的脂质水平的定量测量也有助于评估 常用药物的治疗作用，例如降低胆固醇或胰岛素敏化剂。