Phosphatidylserine headgroup diastereomers translocate equivalently across human erythrocyte membranes

Abstract The natural chiral phospholipid substrates for the plasma membrane aminophospholipid translocator are L -α-phosphatidyl- L -serine and L -α-phosphatidylethanolamine. The glyceric D -stereoisomers of these lipids, D -α-phosphatidyl- L -serine and D -α-phosphatidylethanolamine, are not translocated (Martin, O.C. and Pagano, R.E. (1987) J. Biol. Chem. 262, 5890–5898). We have synthesized a diastereomer of phosphatidylserine, L -α-phosphatidyl- D -serine, to study the effects of headgroup stereochemistry on translocation. The diastereomer was synthesized as the dilauroyl (12:0) species, and the translocation was monitored by human erythrocyte morphology changes at 25°C and 37°C. Unlike other phosphatidylserine stereoisomers, L -α-phosphatidyl- D serine is translocated to the same degree as the natural L,L -isomer. Incorporation of apparently equal amounts of the L,D - and L,L -diastereomers does produce minor quantitative differences in the cell morphological response, possibly as a result of differences in lipid packing of the two isomers.