Role of membrane-associated and cytoplasmic fatty acid-binding proteins in cellular fatty acid metabolism

Role of membrane-associated and cytoplasmic fatty acid-binding proteins in cellular fatty acid metabolism
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DOI:
10.1016/s0952-3278(97)90413-0
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发表时间:
1997-10-01
影响因子:
3
通讯作者:
vanderVusse, GJ
vanderVusse, GJ
中科院分区:
医学4区
文献类型:
--
作者:
Glatz, JFC;vanNieuwenhoven, FA;vanderVusse, GJ

文献摘要

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许多膜相关和细胞质脂肪酸结合蛋白(FABP)现在被牵连在细胞摄取和细胞内转运的长链脂肪酸(FA)。这些蛋白质各自具有非共价结合FA的能力,存在于积极参与FA代谢的组织中,并且在细胞FA代谢增加的条件下上调。迄今为止,已经描述了五种不同的膜FABPs,质量范围为22至88 kDa,并且每种都显示出特征性的组织分布。参与细胞脂肪酸摄取的证据已经提供了其中几个,因为它是最近发现,孤立的细胞系转染88-kDa推定的脂肪酸转位酶(FAT;同源的CD 36)或63-kDa的脂肪酸转运蛋白显示出增加的FA摄取率。细胞质来源的(至少九种)FABP属于小(14-15 kDa)脂质结合蛋白家族,所有FABP具有相似的三级结构,但在结合特性和组织发生方面不同。各种FABP的生物学功能,可能发挥在它们之间的协同作用,包括溶解和区室化的FA,促进细胞摄取和细胞内运输的FA,和有丝分裂,细胞生长和细胞分化的调制。此外,FABP被认为参与和/或调节FA介导的信号转导途径和基因表达的FA调节,并防止局部高FA浓度,从而有助于保护细胞免受FA的毒性作用。总之,长链脂肪酸与多种蛋白质持续相互作用,相互作用影响其细胞代谢。
A number of membrane-associated and cytoplasmic fatty acid-binding proteins (FABPs) are now being implicated in the cellular uptake and intracellular transport of long-chain fatty acids (FA). These proteins each have the capacity of non-covalent binding of FA, are present in tissues actively involved in FA metabolism, and are upregulated in conditions of increased cellular FA metabolism. To date, five distinct membrane FABPs have been described, ranging in mass from 22 to 88 kDa and each showing a characteristic tissue distribution. Evidence for involvement in cellular fatty acid uptake has been provided for several of them, because it was recently found that isolated cell lines transfected with 88-kDa putative fatty acid translocase (FAT; homologous to CD36) or with 63-kDa fatty acid-transport protein show an increased rate of FA uptake. The (at least nine) FABPs of cytoplasmic origin belong to a family of small (14-15 kDa) lipid binding proteins, all having a similar tertiairy structure but differing in binding properties and in tissue occurrence. The biological functions of the various FABPs, possibly exerted in a concerted action among them, comprise solubilization and compartmentalization of FA, facilitation of the cellular uptake and intracellular trafficking of FA, and modulation of mitosis, cell growth, and cell differentiation. In addition, the FABPs have been suggested to participate in and/or modulate FA-mediated signal transduction pathways and FA regulation of gene expression, and to prevent local high FA concentrations thereby contributing to the protection of cells against the toxic effects of FA. In conclusion, long-chain fatty acids are subject to continuous interaction with multiple proteins, which interplay influences their cellular metabolism.