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脂肪酸的细胞摄取及细胞内转运的分子机制

Molecular mechanism of cellular uptake and intracellular translocation of fatty acids.

作者信息

Glatz J F, Luiken J J, van Nieuwenhoven F A, Van der Vusse G J

机构信息

Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, the Netherlands.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 1997 Jul;57(1):3-9. doi: 10.1016/s0952-3278(97)90485-3.

DOI:10.1016/s0952-3278(97)90485-3
PMID:9250601
Abstract

The molecular mechanism of the transport of long-chain fatty acids across cellular membranes and the necessity and precise functioning of specific proteins in this process are still unclear. Various alternative mechanisms have been proposed. Studies with artificial phospholipid bilayers support the concept that fatty acids may enter and traverse the plasma membrane without the involvement of proteins. On the other hand, a number of membrane-associated fatty acid-binding proteins (FABPs) have been described which putatively function as acceptors for fatty acids released from albumin or from lipoproteins. Albumin binding proteins located at the outer cell surface could play an additional role in the delivery of fatty acids. The subsequent transmembrane translocation of fatty acids could take place by a membrane protein acting as a translocase, or by simple diffusion of fatty acids through either the phospholipid bilayer or a pore or channel formed by one or more membrane fatty acid transporters. At the inner side of the plasma membrane, the fatty acid is bound to a cytoplasmic FABP, which serves to buffer the intracellular aqueous fatty acid concentration. The direction of fatty acid migration through the plasma membrane most likely is governed by the transmembrane gradient of fatty acid concentration, assisted to some extent and in selected tissues by co-transport of sodium ions. The intracellular transport of fatty acids from the plasma membrane to the sites of metabolic conversion (oxidation, esterification) or subcellular target (signal transduction) is greatly facilitated by cytoplasmic FABPs. In conclusion, cellular uptake and intracellular translocation of long-chain fatty acids is a multi-step process that is facilitated by various membrane-associated and soluble proteins. The mechanism of cellular uptake of fatty acids probably involves both a passive and carrier-mediated transmembrane translocation.

摘要

长链脂肪酸跨细胞膜转运的分子机制以及特定蛋白质在此过程中的必要性和精确功能仍不清楚。已经提出了各种替代机制。对人工磷脂双层的研究支持了脂肪酸可能在不涉及蛋白质的情况下进入并穿过质膜的概念。另一方面,已经描述了许多与膜相关的脂肪酸结合蛋白(FABP),它们被认为作为从白蛋白或脂蛋白释放的脂肪酸的受体发挥作用。位于细胞外表面的白蛋白结合蛋白可能在脂肪酸的递送中发挥额外作用。脂肪酸随后的跨膜转运可能通过作为转位酶的膜蛋白发生,或者通过脂肪酸简单扩散穿过磷脂双层或由一种或多种膜脂肪酸转运蛋白形成的孔或通道发生。在质膜内侧,脂肪酸与细胞质FABP结合,其用于缓冲细胞内水性脂肪酸浓度。脂肪酸穿过质膜的迁移方向很可能由脂肪酸浓度的跨膜梯度决定,在某些组织中在一定程度上由钠离子的共转运辅助。细胞质FABP极大地促进了脂肪酸从质膜到代谢转化(氧化、酯化)部位或亚细胞靶点(信号转导)的细胞内转运。总之,长链脂肪酸的细胞摄取和细胞内转运是一个多步骤过程,由各种与膜相关的和可溶性蛋白质促进。脂肪酸的细胞摄取机制可能涉及被动和载体介导的跨膜转运。

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