PHOSPHOLIPID TRANSFER DURING INTESTINAL ABSORPTION

这项建议的长期目标是了解这些机制 参与磷脂的消化和吸收 肠子。西方成年人平均摄取约4-8克磷脂 每天另有7-21克被分泌到肠腔 通过胆汁。这些磷脂，溶血磷脂和脂肪 胰腺磷脂酶A2消化产生的酸，混合形式 肠腔内有双层小泡和混合胶束。这些 聚集体是溶解其他肠道脂质和 消化产品(例如，胆固醇、单甘酯、双甘酯和 脂溶维生素，并为运输提供水溶的交通工具 到笔刷边界膜面。一旦被粘膜吸收 细胞，部分溶血磷脂被酰化以提供 磷脂表面涂层用于形成乳胶粒和极低 携带大量吸收的胆固醇的密度脂蛋白， 甘油三酯和其他类脂进入循环。因此，磷脂 消化和吸收与肠道密不可分。 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 哺乳动物小肠对磷脂的吸收：1)如何 磷脂是从混合脂泡和胶束中转移的吗？ 它们被溶解在肠腔中，到达刷子边缘 排列在肠壁上的粘膜细胞的膜？2)如何 胆盐可提高磷脂在水中的转移速度 环境？3)生物化学和功能特征是什么？ 最近提纯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？ 荧光探针标记磷脂和溶血磷脂 NBD(7-硝基-2，1，3-苯并恶二唑-4-基)将用于研究每一个 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物化学 脂肪吸收的机制。

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.