Function of ileal lipid binding protein

脂肪酸结合蛋白(FABP)是一种含量丰富的小分子可溶性蛋白质，广泛存在于各种组织中。某些种类的FABP与某些组织类型有关。这些蛋白质共享相似的3D结构，尽管它们的一级结构有很大的不同。一级结构上的差异可能是导致它们对配体的偏好的原因。这些蛋白质的生理功能还不是很清楚。这表明这些蛋白质在它们各自的配体的细胞运输和储存中起着重要的作用，这些配体是小分子疏水化合物。利用靶向基因技术在小鼠身上进行的研究表明，这些蛋白质的丢失会影响它们各自配体的新陈代谢。也有人认为，FABP可能参与了基因表达的调控，它是内化配体的膜结合转运蛋白和与靶基因启动子结合的同源核受体之间的细胞内穿梭。回肠脂结合蛋白(ILBP)最初定位于小肠远端。ILBP既能结合脂肪酸，又能结合胆汁酸。胆汁酸是由肝脏从胆固醇合成的两亲性分子，对脂类和脂溶营养素的溶解和吸收是必不可少的。一些研究人员认为，由于ILBP与胆汁酸的亲和力更强，因此ILBP在胆汁酸的转运和代谢中发挥着重要作用。然而，最近在卵巢中也检测到ILBP，这增加了这种蛋白可能具有超越胆汁酸代谢的生理功能的可能性。拟议的研究计划围绕三个主题构建。在主题I下，我们将以小鼠为研究模型系统，探讨ILBP在胆汁酸代谢中的生理功能。在主题II下，我们将分析ILBP在非肠道细胞中的作用，例如卵巢细胞。在主题III下，我们将探索ILBP配体结合的分子决定因素。这项拟议的研究有望为ILBP生物学提供新的见解，并促进我们对FABP作用的总体理解。

Fatty acid binding proteins (FABPs) are abundant, small molecular weight soluble proteins found in a wide variety of tissues. Certain species of FABPs are associated with certain tissue types. These proteins share similar 3D structures despite significant dissimilarity in their primary structures. The divergence in primary structure likely contributes to their preference of ligands. The physiological function of these proteins is not precisely known. It is suggested that these proteins play an important role in the cellular transport and storage of their respective ligands, which are small hydrophobic compounds. Studies using targeted gene technology in mice suggest that the loss of these proteins affects the metabolism of their respective ligands. It has also been suggested that FABPs may be involved in regulation of gene expression, by serving as the intracellular shuttle between the membrane-bound transporter that internalizes the ligand and the cognate nuclear receptor that is bound to the promoters of target genes. The ileal lipid binding protein (ilbp) was initially localized in the distal portion of the small intestine. Ilbp can bind both fatty acids and bile acids. Bile acids are amphipathic molecules synthesized by the liver from cholesterol, and are essential for the solubilization and absorption of lipids and lipid-soluble nutrients. Some investigators have suggested that ilbp plays a major role in bile acid transport and metabolism, due to the greater affinity of ilbp for bile acids. Recently however, ilbp has also been detected in the ovaries, raising the possibility that this protein may have a physiological function beyond bile acid metabolism. The proposed research program is constructed around three themes. Under Theme I, we will explore the physiological function of ILBP in the metabolism of bile acids using mice as a model system of study. Under Theme II, we will analyze the role of ilbp in non-intestinal cells, such as ovary cells. Under Theme III, we will probe the molecular determinants of ilbp ligand binding. The proposed research is anticipated to give new insights on ilbp biology as well as advance our general understanding of FABP action.