Docosahexaenoic acid. An influential membrane-altering omega-3 fatty acid
Chapter
Overview
Identity
Additional Document Info
View All
Overview
abstract
Docosahexaenoic acid (DHA), with 22 carbons and 6 double bonds, is the longest and most unsaturated omega-3 fatty acid commonly found in living systems and can be easily manipulated through diet. It has been linked to the alleviation of a multitude of human afflictions including neurological disorders, heart disease and cancer. How one simple molecule can affect so many seemingly unrelated processes remains a mystery. Whatever DHA's mode of action, it must be functioning at a basic level common to a wide variety of cells. We believe that in part DHA's role is in affecting membrane structure and function. Membranes are very complex, heterogeneous mixtures of hundreds of different lipids and scores of proteins that are in dynamic flux. Lipid rafts are a key concept in the current view of membrane structure. They are cholesterol- and sphingolipid-rich domains that serve as cell signaling platforms floating in a sea of more unsaturated phospholipids. We review the effect of DHA on the activity and translocation of several important signaling proteins into and out of rafts. We have developed a model lipid bilayer membrane that addresses the effect on lateral organization of the differential affinity for cholesterol of DHA vs. other less unsaturated fatty acids. The membranes are composed of various mol fractions of cholesterol (CHOL) and sphingomyelin (SM) to which is added phosphatidylcholines (PCs) or phosphatidylethanolamines (PEs). The PCs and PEs are heteroacids with a saturated (palmitic (16:0) or stearic (18:0) acid) sn-1 chain and an unsaturated (oleic acid (OA, 18:1) or DHA (22:6)) sn-2 chain. A greatly enhanced tendency for CHOL and SM to segregate into rafts is indicated for DHA vs. OA by biophysical techniques that include detergent extraction in cold Triton X-100, differential scanning calorimetry, atomic force microscopy, solid state 2H NMR and x-ray diffraction. These experiments establish a significant effect of DHA on membrane structure and function. 2006 by Nova Science Publishers, Inc. All rights reserved.
