Phosphatidylserine headgroup diastereomers translocate equivalently across human erythrocyte membranes.

The natural chiral phospholipid substrates for the plasma membrane aminophospholipid translocator are L-alpha-phosphatidyl-L-serine and L-alpha-phosphatidylethanolamine. The glyceric D-stereoisomers of these lipids, D-alpha-phosphatidyl-L-serine and D-alpha-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-alpha-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 degrees C and 37 degrees C. Unlike other phosphatidylserine stereoisomers, L-alpha-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.