PLASMALOGENS AND RELATED ETHER LIPIDS IN CANCER CELLS

癌细胞中的缩醛磷脂和相关醚脂

• 批准号: 3182372
• 负责人: FRED L SNYDER
• 金额: $ 14.75万
• 依托单位: OAK RIDGE ASSOCIATED UNIVERSITIES
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-30 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3182372
• 关键词: Ehrlich's tumor; acyl group; acyltransferase; alkyl group; cell membrane; chemical cleavage; ethanolamines; ethers; glycolysis; high performance liquid chromatography; laboratory mouse; laboratory rat; ligase; lipid biosynthesis; lipid metabolism; membrane lipids; neoplastic cell; phospholipids; plasmalogens; platelet activating factor; sarcoma; thin layer chromatography

Specific objectives of this application are: (1) to determine the mechanism of how ethanolamine plasmalogens are synthesized from an intact alkyl phospholipid by a 1-alkyl desaturase, (2) to identify the factors that influence branchpoints and to identify the rate-limiting steps in the metabolic pathways for glycerolipids that determine membrane lipid composition with respect to the diacyl-, alkylacyl-, and alk-l-enylacyl- subclasses of phospholipids, and (3) to characterize the properties and to delineate the reaction mechanism and regulatory role of the enzymes that cleave the alkyl (Pte.H4-dependent alkyl monooxygenase) and alk-1-enyl (plasmalogenase) ether bonds in glycerolipids. The studies of the desaturase and the cleavage enzymes are expected to be done with purified preparations of the enzymes. Results of this work are expected to extend our basic understanding of the metabolism of lipids with ether-linked chains, including those phospholipids that are precursors of the alkylacetylated types (e.g., platelet activating factor) that exhibit potent biological activities. Information from these experiments are also expected to explain why ether lipids are characteristically elevated in most cancer cells and could shed light on their functional role in cell membranes.

本申请的具体目标是：(1)确定 乙醇胺类血浆原合成机理的研究 烷基磷脂经1-烷基去饱和酶，(2)鉴定影响因素 中的速率限制步骤。 决定膜脂的甘油脂代谢途径 关于二酰基、烷基酰基和烷基-L-烯酰基的组合物 磷脂的亚类，以及(3)表征性质和 描述了这些酶的反应机制和调节作用 切断烷基(Pte.H4依赖的烷基单加氧酶)和ALK-1-烯基 甘油脂中的(血浆丙二酸酶)醚键。对中国传统文化的研究 去饱和酶和裂解酶预计要用纯化的 酶的制备。 这项工作的成果有望扩大我们对 含醚链的脂类的代谢，包括那些 作为烷基乙酰化类型的前体的磷脂(例如， 血小板激活因子)，具有很强的生物活性。 来自这些实验的信息也有望解释为什么以太 脂类在大多数癌细胞中都有明显的升高，并可能 阐明它们在细胞膜中的功能作用。