Original Article

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

Correspondence to: John S. Parks.

The effects of polyunsaturated fatty acids (PUFA) on the structure of recombinant high density lipoprotein (rHDL) was investigated using homogeneous particles containing phosphatidylcholine (PC), [³H]cholesterol, and apolipoprotein 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 (PDPC). The concentration of guanidine HCl (D_1/2) required to denature one-half of the apoA-I on rHDL containing long chain PUFA was reduced (1.57–1.70 M) compared to those containing POPC (2.83 M). Intrinsic apoA-I tryptophan fluorescence emission intensity and lifetimes were decreased for rHDL containing long chain PUFA compared to POPC and PLPC rHDL. Monoclonal antibody binding studies demonstrated that apoA-I had decreased immunoreactivity with monoclonal antibodies spanning amino acid residues 115–147 in rHDL containing long chain PUFA. PC lipid fluidity, measured as diphenylhexatriene (DPH) 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 conclude that rHDL with long chain PUFA in the sn -2 position of PC contain apoA-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 weaker interaction of apoA-I with PC containing PUFA may lead to hypercatabolism of apoA-I in plasma explaining, in part, the decreased plasma HDL and apoA-I concentrations seen with PUFA diets.—Huggins, K. W., L. K. Curtiss, A. K. Gebre, and J. S. Parks. 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. J. Lipid Res. 1998. 39: 2423–2431.

Supplementary key words: fluorescence spectroscopy, lecithin:cholesterol acyltransferase, circular dichroism, monoclonal antibodies, fluidity

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