POLYUNSATURATED PHOSPHOLIPIDS IN MEMBRANE FUNCTION

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We have had a long-standing interest in membrane phosphoglycerides that contain esterified fatty acids with 4 to 6 cis double bonds. These fatty acids are members of families of polyunsaturated fatty acids that cannot be formed de novo by primates or other vertebrates, and must be provided in the diet if these animals are to reproduce, develop, grow, and maintain their health. The fatty acids also are of interest because they are subject to artifactual oxidation and to special mechanisms to prevent this oxidation and repair its effects, and there is reason to believe that disorders of these mechanisms occur in aged individuals, in atherosclerosis, and in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. We have been exploring the possibility that phosphoglycerides that contain polyunsaturated fatty acids with four or more cis double bonds may normally have an important structural effect on the nerve plasm a membrane lipid bilayer. We are in the process of completing detailed molecular modeling studies to identify factors that might influence the ability of the phosphoglycerides to interact with each other in simulated monolayers. We have almost completed an experimental study of the packing of these phosphoglycerides in monolayers. Experiments with unilamellar vesicles containing the phosphoglycerides are underway, and experiments with macaque brain prefrontal cortex synaptosome plasma membranes and synaptic vesicles (see above) are planned. FUNDING NIH grant RR00166 and the Howard Hughes Medical Institute.