title: Amphipathic helixes and plasma lipoproteins: thermodynamic and geometric considerations.
abstract: 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.
mesh_terms: 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
chemical_list: D001053:Apolipoproteins; D008074:Lipoproteins; D010743:Phospholipids