Lysosomes substrate uptake

However, in addition to this receptor-mediated LDL uptake, cells can also internalize LDL by a bulk-phase pinocytosis which does not require specific cell-surface binding. In this situation LDL is taken up at a rate proportional to the environmental concentration. At low extracellular LDL concentrations the bulk process is insignificant when compared to the receptor mediated uptake. However at elevated LDL concentrations although receptor-mediated uptake becomes rapidly saturated, bulk phase pinocytosis increases in rate proportionately to the overall LDL concentration. The smooth muscle cells in the normal atherosclerotic lesion accumulate lipid by this receptor-independent process which is not subject to feedback control. In addition to this a relative deficiency of lysosomal cholesteryl ester hydrolase activity in the presence of overwhelming concentrations of substrate may also contribute to the aggrevated situation. 

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