Abstract Five separate low density lipoproteins (LD lipoproteins) have been isolated from the plasma of a group of subjects with the disease hyper-pre-β-lipoproteinemia. These lipoproteins have been shown to be discrete, stable components within the LD lipoprotein class which may be isolated repeatedly, by differential density ultracentrifugation, from the serum of these subjects. Immunological study of the delipidized apoproteins shows only a reactivity with the LD lipoprotein antiserum. Electron microscopy reveals spherical macromolecules. Their sedimentation coefficients and hydrated densities have been measured, and their calculated average molecular weights are 4.9, 4.3, 3.2, 2.5, and 1.3 million. Compositional studies show an increasing lipid content with increasing molecular size. Of particular interest is the observation that the mass of protein per mole of lipoprotein remains constant although the molecular weight of these lipoproteins more than doubles, and thus the LD liproprotein components differ only in their lipid content. On the basis of equilibrium-banding experiments in linear density gradients, it is concluded that these lipoproteins exist within the LD lipoprotein class as discrete entities which presumably constitute energetically favorable associations of lipid and protein. Based on the sequential nature of their molecular weights and their known composition, it appears that these lipoproteins may be generated by the addition of specific increments or packets of lipid consisting of multiples of 6.25 x 105 g per mole of lipoprotein. It is postulated that the periodicity observed in the molecular weights reflects the structural limitations imposed upon these macromolecules by the apoprotein which determines the amount of lipid which may be bound. The marked density and molecular weight heterogeneity observed within the lipoproteins constituting the LD lipoprotein class in these subjects with the disease hyper-pre-β-lipoproteinemia is in apparent contrast to that observed with LD lipoprotein from normal subjects. It is thus tempting to speculate that a structurally altered apoprotein occurs in these patients which binds lipid in an atypical fashion and thus generates the multiple components found within the LD lipoprotein class of these subjects with this familial disease.
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