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神经组织中的脂肪酸结合蛋白

Fatty acid-binding proteins of nervous tissue.

作者信息

Veerkamp J H, Zimmerman A W

机构信息

Department of Biochemistry, University Medical Center St. Radboud, Nijmegen, The Netherlands.

出版信息

J Mol Neurosci. 2001 Apr-Jun;16(2-3):133-42; discussion 151-7. doi: 10.1385/JMN:16:2-3:133.

Abstract

Fatty acid-binding proteins (FABPs) are cytosolic 14-15 kDa proteins, which are supposed to be involved in fatty acid (FA) uptake, transport, and targeting. They may modulate FA concentration and in this way influence function of enzymes, membranes, ion channels and receptors, and gene expression and cellular growth and differentiation. Nine FABP types can be discerned with a specific tissue distribution. In spite of 30-70% amino acid sequence identity, they have a similar tertiary, beta-clam structure in which the FA is bound. Nervous tissue contains four FABP types with a distinct spatio-temporal distribution. Myelin (M)-FABP is only present in the peripheral nerves, brain (B)-FABP and epidermal (E)-FABP mainly in glial cells and neurons, respectively of pre- and perinatal brain, and heart (H)-FABP in adult brain. Possible functions of FABPs in the nervous system are discussed. Binding studies with a range of physiological FA showed no large differences between recombinant proteins of the four human FABP types in binding specificity and affinity, also not for polyunsaturated FA (PUFA). The transfer of FA from fixed liposomes to mitochondria was similarly promoted by the four types. A marked difference in conformational stability was observed with H-FABP > B-FABP > M-FABP > E-FABP. Surface epitopes of H-FABP showed reaction with anti-B-FABP antibodies, but no other cross-reactivity of FABP type and heterologous antibodies was observed. The functional significance of the distinct spatio-temporal pattern of the four FABP types remains to be elucidated.

摘要

脂肪酸结合蛋白(FABPs)是一种胞质内14 - 15 kDa的蛋白质,被认为参与脂肪酸(FA)的摄取、转运和靶向作用。它们可能调节脂肪酸浓度,进而影响酶、膜、离子通道和受体的功能,以及基因表达和细胞生长与分化。可识别出九种具有特定组织分布的FABP类型。尽管它们的氨基酸序列同一性为30 - 70%,但它们具有相似的三级β-蛤结构,脂肪酸结合于其中。神经组织含有四种具有独特时空分布的FABP类型。髓磷脂(M)-FABP仅存在于外周神经中,脑(B)-FABP和表皮(E)-FABP分别主要存在于围产期和产前脑的神经胶质细胞和神经元中,而心脏(H)-FABP存在于成体脑中。本文讨论了FABPs在神经系统中的可能功能。对一系列生理脂肪酸的结合研究表明,四种人类FABP类型的重组蛋白在结合特异性和亲和力方面没有显著差异,对多不饱和脂肪酸(PUFA)也是如此。四种类型对脂肪酸从固定脂质体向线粒体的转移促进作用相似。观察到构象稳定性存在显著差异,顺序为H-FABP > B-FABP > M-FABP > E-FABP。H-FABP的表面表位与抗B-FABP抗体发生反应,但未观察到其他FABP类型与异源抗体之间的交叉反应。四种FABP类型独特的时空模式的功能意义仍有待阐明。

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