Effect of acylglyceride content on the structure and function of reconstituted high density lipoprotein particles

The effects of different acylglycerides on the conformation and charge of apolipoprotein A-I (apoA-I) have been investigated in reconstituted high density lipoproteins (LpA-I). Various amounts of diacylglycerol (DG) and triacylglycerol (TG) were incorporated into sonicated spherical LpA-I particles containing 2 molecules of apoA-I and 80 molecules of phospholipid. Inclusion of 30 molecules of TG into the LpA-I particle increases the net negative charge of apoA-I (-8.5 to -9.3 mV), but has little effect on the amount and thermodynamic stability of the alpha helices in apoA-I. Incorporation of 30 molecules of DG into the lipoprotein complex promotes a small increase in the alpha-helix content and stability, but greatly increases the net negative charge of apoA-I (-8.5 to -11.2 mV). Inclusion of DG increases the immunoreactivity of two epitopes in the N terminus of apoA-I, but decreases the exposure of a domain closer to the C terminus (residues 148;-186) of the apoprotein. In contrast, TG increases the exposure of epitopes over the entire apoA-I molecule; TG increases the immunoreactivity of epitopes for 13 different monoclonal antibodies to apoA-I. Incubations with purified lecithin:cholesterol acyltransferase show that cholesterol esterification is stimulated by DG, but inhibited by TG. The data show that TG and DG have different effects on apoA-I structure and function and this suggests that the TG-to-DG ratio in HDL may directly affect the metabolism of this lipoprotein class. - Braschi, S., C. R. Coffill, T. A-M. Neville, D. M. Hutt, and D. L. Sparks. Effect of acylglyceride content on the structure and function of reconstituted high density lipoprotein particles. J. Lipid Res. 2001. 42: 79;-87.