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.
Braschi
S
S
Université de Paris XII and Service de Medecine Interne V, Hôpital Henri Mondor, Creteil, France.
Coffill
C R
CR
Neville
T A
TA
Hutt
D M
DM
Sparks
D L
DL
D000911:Antibodies, Monoclonal; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism / Q000494:pharmacology; D004355:Drug Stability; D000939:Epitopes / Q000187:drug effects; D005989:Glycerides / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D017270:Lipoprotein(a) / Q000031:analogs & derivatives / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary / Q000187:drug effects; D055672:Static Electricity; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000378:metabolism / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D016632:Apolipoprotein A-I; D004075:Diglycerides; D000939:Epitopes; D005989:Glycerides; D017270:Lipoprotein(a); D008075:Lipoproteins, HDL; D014280:Triglycerides; C078260:lipoprotein A-I; D007862:Phosphatidylcholine-Sterol O-Acyltransferase