| Abstract
| - The stability of human low-density lipoprotein (LDL), the major cholesterol carrier in plasma,was analyzed by heating samples of different concentrations at a rate from 11 to 90 K/h. Correlation ofthe calorimetric, circular dichroism, fluorescence, turbidity, and electron microscopic data shows thatthermal disruption of LDL involves irreversible changes in the particle morphology and proteinconformation but no global protein unfolding. Heating to 85 °C induces LDL conversion into smaller andlarger particles and apparent partial dissociation, but not unfolding, of its sole protein, apoB. Furtherheating leads to partial unfolding of the β-sheets in apoB and to fusion of the protein-depleted LDL intolarge aggregated lipid droplets, resulting in a previously unidentified high-temperature calorimetric peak.These lipid droplets resemble in size and morphology the extracellular lipid deposits formed in the arterialwall in early atherosclerosis. The strong concentration dependence of LDL fusion revealed by near-UV/visible CD, turbidity, and calorimetry indicates high reaction order, and the heating rate dependence suggestshigh activation energy that arises from transient disruption of lipid and/or protein packing interactions inthe course of particle fusion and apparent apoB dissociation. Consequently, thermal stability of LDL ismodulated by kinetic barriers. Similar barriers may confer structural integrity to LDL subclasses in vivo.
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