FUNCTION AND REGULATION OF FATTY ACID BINDING PROTEINS

两种结构和免疫学上不同的脂肪酸结合蛋白 已从肝和小肠的胞质溶胶中纯化。 之一 这些蛋白质在肝脏中大量存在（hFABP，14，184 Da）， 大量存在于小肠上皮中， 用等量的不同肠FABP（gFABP，15，063 Da）。 在心肌中发现的第三个Mr 12，000 FABP似乎是不同的 从hFABP和gFABP两者。 此外，hFABP作为四个 肝脏中免疫学上相同的同种型，其显示出显著的差异 结合内源性脂肪酸，包括花生四烯酸。 调控 hFABP受性类固醇激素和降血脂药物的继发作用 hFABP mRNA的变化;脂肪酸在介导这种调节中的作用 研究表明它们也可以调节hFABP 浓度. 这项建议的目的有两个：1）阐明 FABPs的细胞内功能，强调其可能的 在脂肪酸的细胞内区室化中的作用。 朝着这个 最后，提出了研究脂肪酸结合的实验。 使用体外竞争性结合测定的纯FABP的性质， 以及脂肪酸在两种肠道FABP之间的分配 体内给药后。 FABP有可能 差异化地将脂肪酸导向不同的利用途径 将通过检查纯蛋白质对 酶活性和脂肪酸利用途径的体外研究。 2)到 进一步阐明hFABP受激素调节的机制， 药理学和饮食因素，通过测试的假设，脂肪 酸可以介导这种调节。 hFABP浓度的调节 以及肝脏和肠道中mRNA的积累作为膳食脂肪的函数 内容和组成将为此目的进行研究，随后将 研究脂肪酸对hFABP浓度的影响， 在肝细胞单层培养物中的合成。 拟议的研究将增加 关于该机构的职能和管理的大量新资料， FABPs，并因此将提供新的见解，他们在细胞中的作用， 调节脂质代谢。

Two structurally and immunologically distinct fatty acid binding proteins have been purified from the cytosol of liver and small intestine. One of these proteins occurs abundantly in liver (hFABP, 14,184 Da) and is also present in substantial quantities in small intestinal epithelium together with equivalent quantities of a distinct intestinal FABP (gFABP, 15,063 Da). A third Mr 12,000 FABP found in myocardium appears to be distinct from both hFABP and gFABP. In addition, hFABP exists as four immunologically identical isoforms in liver, which show marked differences in bound endogenous fatty acids, including arachidonic acid. Regulation of hFABP by sex steroid hormones and hypo-lipidemic drugs is secondary to changes in hFABP mRNA; a role for fatty acids in mediating this regulation has been suggested by studies showing that they too may modulate hFABP concentration. The aims of this proposal are two-fold: 1) To elucidate the intracellular function of the FABPs with emphasis on their possible role in the intracellular compartmentation of fatty acids. Toward this end, experiments are propossed which will study the fatty acid binding properties of the pure FABPs using an in vitro competitive binding assay, as well as the partition of fatty acids between the two intestinal FABPs following in vivo administration. The possibility that the FABPs differentially direct fatty acids towards different pathways of utilization will be tested by examining the effects of the pure proteins on the activity of enzymes and pathways of fatty acid utilization in vitro. 2) To further elucidate the mechanism whereby hFABP is regulated by hormonal, pharmacological and dietary factors by testing the hypothesis that fatty acids may mediate this regulation. The modulation of hFABP concentration and mRNA accumulation in liver and intestine as a function of dietary fat content and composition will be studied toward this end will be followed by studies of the influence of fatty acids on hFABP concentration and synthesis in hepatocyte monolayer cultures. The proposed studies will add substantial new information regarding the function and regulation of the FABPs, and will thus provide new insight into their role in the cellular regulation in lipid metabolism.