Structural determinants of the packing and electrostatic behavior of unsaturated phosphoglycerides.

Docosahexaenoic acid-containing phosphoglycerides accumulate preferentially in membranes of the retina, brain, and spermatozoa, but the functional significance of this largely remains to be determined. Previously we compared the physical properties of homogeneous monolayers of these and other phosphoglyceride species to obtain insights into their physiological roles. Particularly noteworthy were the unusually low dipole moments of species having sn-2-docosahexaenoyl chains. In this study, we have investigated the electrostatic and lateral packing properties of related phosphoglycerides and found that: 1), The dipole moment-lowering effect of the docosahexaenoyl group arises from its having a Z double bond at chain position n-3. 2), The large dipole moment-lowering effects at sn-1 of an ether bond to an alkyl or a 1Z alkenyl chain and that of a sn-2-esterified n-3 fatty acid are additive. 3), The 1Z double bond in an alkenyl chain lowers the molecular area of a phosphoglyceride and, concomitantly, makes it less compressible. 4), Ethanolamine-containing phosphoglycerides are generally less compressible than their corresponding choline analogs. Our data showing that relatively small lipid structural changes markedly alter lipid physical properties in fluid phases underscores the need to study the function of peripheral and integral membrane proteins in the presence of appropriate lipid species.