Glatz Jan F C
Department of Genetics & Cell Biology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Prostaglandins Leukot Essent Fatty Acids. 2015 Feb;93:45-9. doi: 10.1016/j.plefa.2014.07.011. Epub 2014 Jul 19.
Lipids serve a great variety of functions, ranging from structural components of biological membranes to signaling molecules affecting various cellular functions. Several of these functions are related to the unique physico-chemical properties shared by all lipid species, i.e., their hydrophobicity. The latter, however, is accompanied by a poor solubility in an aqueous environment and thus a severe limitation in the transport of lipids in aqueous compartments such as blood plasma and the cellular soluble cytoplasm. Specific proteins which can reversibly and non-covalently associate with lipids, designated as lipid binding proteins or lipid chaperones, greatly enhance the aqueous solubility of lipids and facilitate their transport between tissues and within tissue cells. Importantly, transport of lipids across biological membranes also is facilitated by specific (membrane-associated) lipid binding proteins. Together, these lipid binding proteins determine the bio-availability of their ligands, and thereby markedly influence the subsequent processing, utilization, or signaling effect of lipids. The bio-availability of specific lipid species thus is governed by the presence of specific lipid binding proteins, the affinity of these proteins for distinct lipid species, and the presence of competing ligands (including pharmaceutical compounds). Recent studies suggest that post-translational modifications of lipid binding proteins may have great impact on lipid-protein interactions. As a result, several levels of regulation exist that together determine the bio-availability of lipid species. This short review discusses the significance of lipid binding proteins and their potential application as targets for therapeutic intervention.
脂质具有多种功能,从生物膜的结构成分到影响各种细胞功能的信号分子。其中一些功能与所有脂质种类共有的独特物理化学性质有关,即它们的疏水性。然而,疏水性伴随着在水性环境中的低溶解度,因此在诸如血浆和细胞可溶性细胞质等水性隔室中脂质运输受到严重限制。能够与脂质可逆且非共价结合的特定蛋白质,称为脂质结合蛋白或脂质伴侣,极大地提高了脂质在水中的溶解度,并促进它们在组织之间以及组织细胞内的运输。重要的是,特定的(膜相关的)脂质结合蛋白也促进脂质跨生物膜的运输。这些脂质结合蛋白共同决定了其配体的生物利用度,从而显著影响脂质的后续加工、利用或信号传导效应。因此,特定脂质种类的生物利用度受特定脂质结合蛋白的存在、这些蛋白对不同脂质种类的亲和力以及竞争性配体(包括药物化合物)的存在所支配。最近的研究表明,脂质结合蛋白的翻译后修饰可能对脂质 - 蛋白质相互作用有很大影响。因此,存在多个调节水平,它们共同决定脂质种类的生物利用度。这篇简短的综述讨论了脂质结合蛋白的重要性及其作为治疗干预靶点的潜在应用。