MOLECULAR-SPECIES OF MEMBRANE PHOSPHOLIPIDS CONTAINING ARACHIDONIC-ACID AND LINOLEIC-ACID CONTRIBUTE TO THE INTERINDIVIDUAL VARIABILITY OF RED-BLOOD-CELL NA-LI+ COUNTERTRANSPORT - INVIVO AND INVITRO EVIDENCE()

Previous studies indicate a particular sensitivity of red blood cell N a+-Li+ countertransport activity to small variations in the fatty acid composition of membrane phospholipids. To assess whether the interind ividual variability of Na+-Li+ countertransport is related to differen ces in the species pattern of erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in vivo, the molecular species composit ion of PC and PE as well as the kinetics of Na+-Li+ countertransport w ere analyzed in parallel in normo- and hyperlipidemic donors. Both in diacyl-PC and in diacyl-PE the species 16:0/20:4 and 16:0/18:2 were, r espectively, positively and negatively related to the apparent maximal velocity of Na+-Li+ countertransport. The sum of all species with 20: 4 at sn2 of diacyl-PE exhibited a strong positive (r = 0.82, 2p < 0.00 1), and those containing 18:2 a negative correlation (r = -0.63, 2p < 0.01) to the transport activity. Essentially similar connections were observed between these species and the apparent affinity of the transp ort system for intracellular Na+. To evaluate whether the associations between molecular species of membrane phospholipids and Na+-Li+ count ertransport activity were indicative of a causal relationship, the spe cies 16:0/20: 4-PC and 16:0/18: 2-PC were selectively introduced into the erythrocyte membrane by means of the PC-specific transfer protein. Replacement of 11% of native PC by 16:0/18:2-PC inhibited the transpo rt rate by about 25%. Exchange of 6 and 9% of PC with 16: 0/20: 4-PC, in contrast, accelerated the transport rate by 30 and 60%, respectivel y. The accordance between the in vivo relations and the results of the in vitro modification strongly suggests that elevations and reduction s in the arachidonic acid and linoleic acid content of membrane PC and PE contribute to the interindividual variability of red blood cell Na +-Li+ countertransport activity and its acceleration in hyperlipidemia s.