Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27834, USA.
J Nutr Biochem. 2012 Feb;23(2):101-5. doi: 10.1016/j.jnutbio.2011.07.001. Epub 2011 Dec 1.
N-3 polyunsaturated fatty acids (PUFAs) from fish oil exert their functional effects by targeting multiple mechanisms. One mechanism to emerge in the past decade is the ability of n-3 PUFA acyl chains to perturb the molecular organization of plasma membrane sphingolipid/cholesterol-enriched lipid raft domains. These domains are nanometer-scale assemblies that coalesce to compartmentalize select proteins for optimal function. Here we review recent evidence on how n-3 PUFAs modify lipid rafts from biophysical and biochemical experiments from several different model systems. A central theme emerges from these studies. N-3 PUFA acyl chains display tremendous conformational flexibility and a low affinity for cholesterol and saturated acyl chains. This unique flexibility of n-3 PUFA acyl chains impacts the organization of inner and outer leaflet lipid rafts by disrupting acyl chain packing and molecular order within rafts. Ultimately, the disruption in raft organization has consequences for protein clustering and thereby signaling. Overall, elucidating the complex mechanisms by which n-3 PUFA acyl chains reorganize membrane architecture will enhance the translation of these fatty acids into the clinic for treating several diseases.
鱼油中的 n-3 多不饱和脂肪酸（PUFAs）通过靶向多种机制发挥其功能作用。在过去十年中出现的一种机制是，n-3 PUFA 酰基链能够扰乱富含神经酰胺和胆固醇的质膜鞘脂/胆固醇富脂筏域的分子组织。这些域是纳米级别的组装体，融合以分隔特定蛋白质以实现最佳功能。在这里，我们回顾了最近的证据，说明 n-3 PUFAs 如何通过来自几个不同模型系统的生物物理和生化实验来修饰脂质筏。这些研究中的一个核心主题是。n-3 PUFA 酰基链显示出巨大的构象灵活性和对胆固醇和饱和酰基链的低亲和力。n-3 PUFA 酰基链的这种独特灵活性通过破坏筏内的酰基链堆积和分子有序性来影响内叶和外叶脂质筏的组织。最终，筏组织的破坏会影响蛋白质聚类，从而影响信号转导。总的来说，阐明 n-3 PUFA 酰基链重组膜结构的复杂机制将增强这些脂肪酸在治疗几种疾病方面的临床应用。
