[Conformation of apolipoprotein B-100--structure and functional classification of low density lipoproteins]

Based on the model of an oil drop of the apolipoprotein B-100 lipoproteins (apo-B-100 LP) structure and physico-chemical and antigenic differences in their individual classes, an alternative model has been developed. If the apo-B-100 contains one hydrophilic ligand domain, two hydrophobic domains with predominating alpha-structures and two domains with predominating beta-folding, the molecule may acquire the conformation of a disc, one side of which is hydrophilic, while the other one is hydrophobic. The hydrophilic side of the disc comprises the ligand domain; on the hydrophobic side apo-B-100 forms nonpolar lipids. Apo-B-100 LP has the structure of a bilayer protein-lipid disc. Stepwise alterations in the apo-B-100 disc configuration during lipolysis determine the conversion of apo-B-100 LP in the blood flow: very low density LP-->low density LP. Conformational changes in the apo-B-100 disc form the basis for antigenic differences in each class of LP. Changes in the conformation of apo-B-100 disc in LP induce lipolysis and the formation of cholesterol esters circulating in the functional cycle, in which the cell is the indispensable step. The functional turnover of cholesterol in tissues integrates into one cycle lipoproteins of both high and low density. Equimolar substitution of triglycerides for more hydrophobic cholesterol esters associated with the C-terminal domain of apo-B-100 receptor of the cell. During triglyceride transport the apo-B-100 disc consecutively acquires three configurations--initial, intermediate and final. This hypothesis made the basis for functional classification of apo-B-100 LP in which the initial, intermediate and final classes can be singled out. Blockade of the functional cycle of cholesterol at various stages gives rise to individual hyperlipoproteinemia phenotypes. LP of one class only are accumulated in the blood for each type: the initial class in type III, the intermediate class in type IIb and the final class in type IIa. Each of the three apo-B-100 LP classes is distinguished for its peculiar structure and significant differences in the mechanism of their reception by the cells.