PHOSPHOLIPID TRANSFER DURING INTESTINAL ABSORPTION

肠道吸收过程中的磷脂转移

• 批准号: 3241061
• 负责人: John Wylie Nichols
• 金额: $ 11.89万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1995-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3241061
• 关键词: brush border membrane; cholanate compound; fluorescent dye /probe; gastrointestinal absorption /transport; laboratory rabbit; lipid solubility; lipid transport; lysophospholipase; lysophospholipids; micelles; phospholipids; small intestines; vesicle /vacuole

The long-term objective of this proposal is to understand the mechanisms involved in the digestion and absorption of phospholipids in the intestine. The average Western adult ingests about 4-8 g of phospholipid per day and another 7-21 g per day are secreted into the intestinal lumen via the bile. These phospholipids, and the lysophospholipids and fatty acids produced by pancreatic phospholipase A2 digestion, form mixed bilayer vesicles and mixed micelles in the intestinal lumen. These aggregates are necessary to solubilize other intestinal lipids and digestion products (e.g. cholesterol, monoglycerides, diglycerides, and fat-soluble vitamins and to provide a water-soluble vehicle for transport to the brush border membrane surface. Once absorbed by the mucosal cells, a portion of the lysophospholipids are reacylated to provide the phospholipid surface coat for the formation of chylomicrons and very low density lipoproteins which carry the bulk of the absorbed cholesterol, triglycerides, and other lipids into the circulation. Thus, phospholipid digestion and absorption are integrally related to the intestinal digestion and absorption of most lipids. The goal of this work is to answer three specific questions related to the absorption of phospholipids in the mammalian small intestine: 1) How are phospholipids transferred from mixed lipid vesicles and micelles, in which they are solubilized in the intestinal lumen, to the brush border membrane of the mucosal cells that line the intestinal wall? 2) How do bile salts increase the rate of phospholipid transfer through the water environment? 3) What are the biochemical and functional characteristics of an apparently new lysophospholipase that has recently been purified from intestinal mucosal brush border membranes, where is it produced, and is it structurally related to other known lipases and esterases? Phospholipids and lysophospholipids labeled with the fluorescent probe NBD (7-nitro-2,1,3-benzoxadiazol-4-yl) will be used to study each of these questions. The answers to these questions will lead directly to a better understanding of the fundamental physical and biochemical mechanisms of lipid absorption.

该提案的长期目标是了解机制 参与磷脂的消化和吸收 肠。 西方成年人平均摄入约 4-8 克磷脂 每天另外7-21克被分泌到肠腔中 通过胆汁。 这些磷脂、溶血磷脂和脂肪 胰磷脂酶 A2 消化产生的酸，形成混合形式 肠腔内有双层囊泡和混合胶束。 这些 聚集体是溶解其他肠道脂质所必需的 消化产物（例如胆固醇、甘油单酯、甘油二酯和 脂溶性维生素并提供水溶性运输载体 至刷状缘膜表面。 一旦被粘膜吸收 在细胞中，一部分溶血磷脂被再酰化以提供 磷脂表面涂层用于形成乳糜微粒并且非常低 密度脂蛋白携带大部分被吸收的胆固醇， 甘油三酯和其他脂质进入循环。 因此，磷脂 消化吸收与肠道密切相关 大多数脂质的消化和吸收。 这项工作的目标是回答与以下相关的三个具体问题 哺乳动物小肠中磷脂的吸收： 1) 如何吸收 是从混合脂质囊泡和胶束转移的磷脂， 它们溶解在肠腔中，直至刷状缘 肠壁上的粘膜细胞膜？ 2）如何做 胆汁盐增加磷脂通过水的转移率 环境？ 3）生化和功能特性是什么 最近纯化的一种明显新的溶血磷脂酶 来自肠粘膜刷状缘膜，它是在哪里产生的，以及 它在结构上与其他已知的脂肪酶和酯酶相关吗？ 用荧光探针标记的磷脂和溶血磷脂 NBD（7-硝基-2,1,3-苯并恶二唑-4-基）将用于研究以下各项 这些问题。 这些问题的答案将直接导致 更好地理解基本的物理和生化 脂质吸收机制。