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

The effects of different acylglycerides on the con- formation and charge of apolipoprotein A-I (apoA-I) have been investigated in reconstituted high density lipoproteins (LpA-I). Various amounts of diacylglycerol (DG) and triacyl- glycerol (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 ( 2 8.5 to 2 9.3 mV), but has little effect on the amount and thermodynamic stability of the a helices in apoA-I. Incorporation of 30 molecules of DG into the lipo- protein complex promotes a small increase in the a -helix content and stability, but greatly increases the net negative charge of apoA-I ( 2 8.5 to 2 11.2 mV). Inclusion of DG in- creases the immunoreactivity of two epitopes in the N ter- minus of apoA-I, but decreases the exposure of a domain closer to the C terminus (residues 148-186) of the apopro- tein. In contrast, TG increases the exposure of epitopes over the entire apoA-I molecule; TG increases the immu- noreactivity of epitopes for 13 different monoclonal anti- bodies to apoA-I. Incubations with purified lecithin:choles- terol 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 lipo- protein particles. J. Lipid Res. 2001. 42: 79-87.