| Abstract
| - Very-low-density lipoproteins (VLDL) are metabolic precursors of low-density lipoproteins(LDL) and a risk factor for atherosclerosis. Human VLDL are heterogeneous complexes containing atriacylglycerol-rich apolar lipid core and polar surface composed of phospholipids, a nonexchangeableapolipoprotein B, and exchangeable apolipoproteins E and Cs. We report the first stability study of VLDL.Circular dichroism and turbidity data reveal an irreversible heat-induced VLDL transition that involvesformation of larger particles and repacking of apolar lipids but no global protein unfolding. Heating rateeffect on the melting temperature indicates a kinetically controlled reaction with high activation energy,Ea. Arrhenius analysis of the turbidity data reveals two kinetic phases with Ea = 53 ± 7 kcal/mol thatcorrespond to distinct morphological transitions observed by electron microscopy. One transition involvesVLDL fusion, partial rupture, and dissociation of small spherical particles (d = 7−15 nm), and anotherinvolves complete lipoprotein disintegration and lipid coalescence into droplets accompanied by dissociationof apolipoprotein B. The small particles, which are unique to VLDL denaturation, are comparable in sizeand density to high-density lipoproteins (HDL); they have an apolar lipid core and polar surface composedof exchangeable apolipoproteins (E and possibly Cs) and phospholipids. We conclude that, similar toHDL and LDL, VLDL are stabilized by kinetic barriers that prevent particle fusion and rupture anddecelerate spontaneous interconversion among lipoprotein classes and subclasses. In addition to fusion,VLDL disruption involves transient formation of HDL-like particles that may mimic protein exchangeamong VLDL and HDL pools in plasma.
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