Wassall Stephen R, Stillwell William
Department of Physics, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202-3273, USA.
Biochim Biophys Acta. 2009 Jan;1788(1):24-32. doi: 10.1016/j.bbamem.2008.10.011. Epub 2008 Oct 30.
Polyunsaturated fatty acids (PUFA) constitute an influential group of molecules that promote health by an as yet unknown mechanism. They are structurally distinguished from less unsaturated fatty acids by the presence of a repeating =CH-CH(2)-CH= unit that produces an extremely flexible chain rapidly reorienting through conformational states. The most highly unsaturated case in point is docosahexaenoic acid (DHA) with 6 double bonds. This review will summarize how the high disorder of DHA affects the properties of the membrane phospholipids into which the PUFA incorporates, focusing upon the profound impact on the interaction with cholesterol. Results obtained with model membranes using an array of biophysical techniques will be presented. They demonstrate DHA and the sterol possesses a mutual aversion that drives the lateral segregation of DHA-containing phospholipids into highly disordered domains away from cholesterol. These domains are compositionally and organizationally the opposite of lipid rafts, the ordered domain enriched in predominantly saturated sphingolipids "glued" together by cholesterol that is believed to serve as the platform for signaling proteins. We hypothesize that DHA-rich domains also form in the plasma membrane and are responsible, in part, for the diverse range of health benefits associated with DHA.
多不饱和脂肪酸（PUFA）是一类具有重要影响力的分子，其通过一种尚不清楚的机制促进健康。它们在结构上与不饱和程度较低的脂肪酸不同，其存在一个重复的=CH-CH(2)-CH=单元，该单元产生了一条极其灵活的链，能通过构象状态快速重新定向。最高度不饱和的例子是含有6个双键的二十二碳六烯酸（DHA）。本综述将总结DHA的高度无序性如何影响PUFA掺入的膜磷脂的性质，重点关注对与胆固醇相互作用的深远影响。将展示使用一系列生物物理技术对模型膜获得的结果。这些结果表明，DHA和固醇相互排斥，这种排斥驱使含DHA的磷脂横向分离成远离胆固醇的高度无序区域。这些区域在组成和组织上与脂筏相反，脂筏是富含主要由胆固醇“黏合”在一起的饱和鞘脂的有序区域，被认为是信号蛋白的平台。我们推测富含DHA的区域也在质膜中形成，并且部分地负责与DHA相关的各种健康益处。
