FATTY ACID TRANSPORT IN THE INTESTINE

描述：本提案的具体目的是：1)确定 消化脂类产品从胶束转移的速率和机制， 囊泡和餐后消化期的混合种群。这些 研究将使用最近开发的实验系统，该系统允许 首席调查员(P.I.)为了定量地检验动力学 鲁米那脂肪酸(FA)和单甘酯(MG)转移的机制；2) 确定两种肠上皮细胞FABP的分子机制 调节FA和MG向膜的转运。私家侦探最近 结果表明，IFABP通过与膜的碰撞作用将FA转移到膜上 膜。这些研究将确定结构域 结合使用定点突变负责这些相互作用 对蛋白质-膜相互作用进行生化和生物物理分析。 此外，MG从LFABP转移到膜上的速率和机理 将被确定，因为最近已经证明，MG是一个 LFABP的特异性配基；以及3)研究IFABP和LFABP在 细胞内FA和MG的摄取和转运。私家侦探此前曾表示， 与实际的肠道细胞不同，Caco-2细胞表达LFABP，但不表达IFABP。在……里面 在这些研究中，P.I.将使用Caco-2细胞，与实际的肠道细胞不同， 只表示LFABP，但不表示IFABP。在这些研究中，私家侦探将使用 野生型或特异性突变型IFABP转染Caco-2细胞 检测L和IFABP对细胞内转运的影响 FA和MG，以及对肠细胞脂代谢的影响。这样做的长期目标是 研究是通过调节来实现对脂质同化的控制。 具体的运输流程。

DESCRIPTION: The specific aims of this proposal are: 1) To determine the rates and mechanisms of transfer of digestive lipid products from micelles, vesicles, and mixed populations of postprandial digestive phases. These studies will use a recently developed experimental system which allows the principal investigator (P.I.) to quantitatively examine the kinetic mechanisms of luminal fatty acid (FA) and monoglyceride (MG) transfer; 2) To determine the molecular mechanisms by which the two enterocyte FABP's modulate the transfer of FA and MG to membranes. The P.I. has recently shown that IFABP transfers FA to membranes by collisional interactions with the membrane. These studies will determine the structural domains responsible for these interactions using site-directed mutagenesis combined with biochemical and biophysical analysis of protein-membrane interactions. In addition, the rate and mechanism of MG transfer from LFABP to membranes will be determined, as it has been recently demonstrated that MG is a specific ligand for LFABP; and 3) To examine the role of IFABP and LFABP in cellular FA and MG uptake and transport. The P.I. has shown previously that Caco-2 cells, unlike actual enterocytes, express LFABP but not IFABP. In these studies, the P.I. will use Caco-2 cells, unlike actual enterocytes, express only LFABP but not IFABP. In these studies, the P.I. will use Caco-2 cells transfected with wild type or specific mutant IFABP's to examine the effects of L- and IFABP on both the intracellular trafficking of FA and MG, and on enterocyte lipid metabolism. The long term goal of this research is to enable the control of lipid assimilation by modulation of specific transport processes.