Effect of long chain polyunsaturated fatty acids in the sn-2 position of phosphatidylcholine on the interaction with recombinant high density lipoprotein apolipoprotein A-I

The effects of polyunsaturated fatty acids (PUFA) on the structure of recom binant high density lipoprotein (rHDL) was investigated using homogeneous p articles containing phosphatidylcholine (PC), [H-3]cholesterol, and apolipo protein A-I (apoA-I). The PC component of the rHDL contained sn-1 16:0 and sn-2 18:1 (POPC), 18:2 (PLPC), 20:4 (PAPC), 20:5 n-3 (PEPC), or 22:6 n-3 (P DPC), The concentration of guanidine HCl (D-1/2) required to denature one-h alf of the apoA-I on rHDL containing long chain PUFA was reduced (1.57-1.70 M) compared to those containing POPC (2.83 hi), Intrinsic apoA-I tryptopha n fluorescence emission intensity and lifetimes were decreased for rHDL con taining long chain PUFA compared to POPC and PLPC rHDL, Monoclonal antibody binding studies demonstrated that apoA-I had decreased immunoreactivity wi th monoclonal antibodies spanning amino acid residues 115-147 in rHDL conta ining long chain PUFA, PC lipid fluidity, measured as diphenylhexatriene (D PH) fluorescence polarization, was increased in PUFA rHDL compared to POPC rHDL, There also was a strong correlation between the number of sn-2 double bonds in rHDL and DPH fluorescence lifetime (r(2) = 0.89), LCAT reactivity of the homogeneous size rHDL was ordered POPC = PLPC>PAPC>PEPC>PDPC. We co nclude that rHDL with long chain PUFA in the sn-2 position of PC contain ap oA-I that is less stable and in a different conformation than that in POPC rHDL and have a fatty acyl region that is more fluid and hydrated. The weak er interaction of apoA-I with PC containing PUFA may lead to hypercatabolis m of apoA-I in plasma explaining, in part, the decreased plasma HDL and apo A-I concentrations seen with PUFA diets.