Decreased binding of apoA-I to phosphatidylcholine monolayers containing 22:6 n-3 in the sn-2 position

Previous studies have shown that dietary fish oil can modify the distribution and fatty acyl composition of plasma phospholipids. Although it is known that the type of phospholipid can affect the binding of apolipoprotein A-I (apoA-I), little is known about the effect of n-3 fatty acid enrichment in phospholipids on apoA-I binding. We hypothesize that phosphatidylcholine (PC) surfaces containing n-3 fatty acids at the sn-2 position bind apoA-I less avidly than those containing sn-2 18:1. PC species containing sn-1 16:0 and sn-2 18:1 (POPC), sn-2 20:5 n-3 (PEPC), or sn-2 22:6 n-3 (PDPC) were used in apoA-I monolayer binding studies. The molecular surface area at any given surface pressure (tau) was ordered: PDPC > PEPC > POPC and at tau = 25 mN/m the molecular surface areas were 86.2, 78.8 and 72 A 2/molecule, respectively. Binding of [14C]apoA-I (radiolabeled by reductive methylation) to PDPC at tau i = 15 mN/m was less than that for POPC whether expressed as nmol A-I/m2 surface or molecules A-I/1000 PC. The apparent Kd for steady state apoA-I binding to PEPC (2.1 nM) and PDPC (2.2 nM) was greater than that for POPC (1.2 nM); the maximum binding capacity (nmol/m2) was ordered PEPC (9.4) > POPC (8.1) > PDPC (6.7). Similar results were found when a fixed amount of apoA-I was injected beneath the PC monolayers equilibrated at different initial surface pressures. The calculated surface area available for bound apoA-I was 15, 17, and 23 A 2/amino acid for POPC, PEPC, and PDPC at tau i = 15 mN/m, respectively. We conclude that the binding affinity of apoA-I for PDPC and PEPC is less than that for POPC and that apoA-I bound to PDPC is more loosely folded than that to POPC. These studies suggest that the type of sn-2 fatty acid can influence apoA-I binding to PC.