Biological membranes contain a substantial amount of PC and PE in which the sn-2 acyl chains are unsaturated hydrocarbons. There is increasing evidence that skeletal muscle phospholipids with specific unsaturated sn-2 acyl chains may be of great significance in modulating the insulin receptor activity (Borkman et al. (1993), NEJM 328, 238; Liu et al. (1994) Biochem. J. 299,831). Also, an optimal function of the brain or retina depends critically on the presence of a highly unsaturated species of phospholipids (Salen & Niebylsk (1995), Mol. Memb. Biol. 12, 131). At present, knowledge of the mechanism by which specific unsaturated phospholipids elicit their essential roles in cell membranes is unknown. It is thus relevant to investigate the structure/property of unsaturated phospholipids, since results obtained may build a mechanistic foundation from which clinically observed abnormalities resulting from the deficiency of unsaturated membrane lipids may be assessed. In the past, this group has gained considerable experience in synthesizing and characterizing the structure/property of saturated mixed-chain PC and PE. Now, the long term objective is to extend the earlier work by directing the efforts towards a new direction, aiming at the elucidation of the structure/property of unsaturated PE and PC in the bilayer. Specifically, PC and PE with distinct chain length, degree of unsaturation, and double bond positions, which resemble strictly the naturally occurring phospholipids, will be synthesized, followed by thermodynamic and structural studies using principally the methods of differential scanning calorimetry and molecular mechanics calculations. In addition, the lipid chain interdigitation of PC induced by alcohols will be examined systematically. Finally, the thermotropic phase behavior of mixed-chain phosphatidylglycerols will be compared with that of PC. Dr. Huang believes that the results of the proposed studies will make genuine advances in the understanding of membrane lipids; in addition, they may lead to many informative new experiments in the future.
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