Amphipathic helixes and plasma lipoproteins: thermodynamic and geometric considerations.
In this paper analyses are made of the thermodynamic and geometric properties of the predicted association between amphipathic helixes and phospholipid vesicles. From thermodynamic considerations it is proposed that a major driving force for such an association is the negative free energy gained by the transfer of a number of hydrophobic residues (contained within the non-polar faces of amphipathic helixes), from water to the interior of a phospholipid bilayer. The mechanism proposed is that in the aqueous state a potentially amphipathic sequence forms a non-helical hydrophobic patch on the surface of the apolipoprotein. Formation of an amphipathic helix and simultaneous burial of the hydrophobic residues in the surface of a phospholipid bilayer provides the driving force for lipid association. From this model an estimate of the upperlimit for the hydrophobically driven free energy of lipid association (-40-65 kcal/mol) is calculated for the 4 apolipoproteins with known sequences. On the basis of geometrical considerations a model for an intermediate state of high density lipoprotein (HDL) synthesis is proposed. This model consists of a cholesterol-containing phospholipid bilayer disc whose 'naked" hydrophobic edges are shielded from the aqueous phase by amphipathic helixes of the apolipoproteins. Exposure of these 'bicycle tire" miscelles to the enzyme lecithin : cholesterol acyl transferase (LCAT) is postulated to result in the formation of mature spherical HDL particles with cholesteryl ester forming a neutral lipid core.
D001053:Apolipoproteins / Q000097:blood; D001665:Binding Sites; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008433:Mathematics; D008854:Microscopy, Electron; D008958:Models, Molecular; D010743:Phospholipids / Q000097:blood; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics
D001053:Apolipoproteins; D008074:Lipoproteins; D010743:Phospholipids