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: 3182371
• 负责人: FRED L SNYDER
• 金额: $ 14.21万
• 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/3182371
• 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 乙醇胺缩醛磷脂是如何从完整的 通过1-烷基去饱和酶测定烷基磷脂，（2）确定因素 影响分支点，并确定限速步骤， 决定膜脂质的甘油脂代谢途径 关于二酰基-、烷基酰基-和烷-1-烯酰基-的组成， 磷脂的亚类，和（3）表征性质， 描述酶的反应机制和调节作用， 裂解烷基（Pte.H4-依赖性烷基单加氧酶）和烯基 （缩醛磷脂酶）甘油脂中的醚键。 的这两份研究报告 去饱和酶和切割酶预期用纯化的 酶的制备。 这项工作的结果预计将扩大我们的基本了解， 具有醚连接链的脂质的代谢，包括那些 作为烷基乙酰化类型的前体的磷脂（例如， 血小板活化因子），其表现出有效的生物活性。 从这些实验中得到的信息也有望解释为什么乙醚 大多数癌细胞中的脂质通常升高，并且可能脱落 了解它们在细胞膜中的功能作用。