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首页> 外文期刊>Biochemistry >Thermal Transitions in Human Very-Low-Density Lipoprotein: Fusion, Rupture, and Dissociation of HDL-like Particles
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Thermal Transitions in Human Very-Low-Density Lipoprotein: Fusion, Rupture, and Dissociation of HDL-like Particles

机译:人类极低密度脂蛋白的热转变:HDL样颗粒的融合,破裂和解离

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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 a triacylglycerol-rich apolar lipid core and polar surface composed of phospholipids, a nonexchangeable apolipoprotein 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 involves formation of larger particles and repacking of apolar lipids but no global protein unfolding. Heating rate effect on the melting temperature indicates a kinetically controlled reaction with high activation energy, E_a. Arrhenius analysis of the turbidity data reveals two kinetic phases with E_a = 53 ± 7 kcal/mol that correspond to distinct morphological transitions observed by electron microscopy. One transition involves VLDL fusion, partial rupture, and dissociation of small spherical particles (d = 7-15 nm), and another involves complete lipoprotein disintegration and lipid coalescence into droplets accompanied by dissociation of apolipoprotein B. The small particles, which are unique to VLDL denaturation, are comparable in size and density to high-density lipoproteins (HDL); they have an apolar lipid core and polar surface composed of exchangeable apolipoproteins (E and possibly Cs) and phospholipids. We conclude that, similar to HDL and LDL, VLDL are stabilized by kinetic barriers that prevent particle fusion and rupture and decelerate spontaneous interconversion among lipoprotein classes and subclasses. In addition to fusion, VLDL disruption involves transient formation of HDL-like particles that may mimic protein exchange among VLDL and HDL pools in plasma.
机译:极低密度脂蛋白(VLDL)是低密度脂蛋白(LDL)的代谢前体,是动脉粥样硬化的危险因素。人VLDL是异质复合物,包含富含三酰基甘油的非极性脂质核心和极性表面,该表面由磷脂,不可交换的载脂蛋白B和可交换的载脂蛋白E和Cs组成。我们报告了VLDL的首次稳定性研究。圆二色性和浊度数据揭示了不可逆的热诱导的VLDL转变,该转变涉及形成更大的颗粒和重新包装非极性脂质,但没有全局蛋白展开。加热速率对熔融温度的影响表明具有高活化能E_a的动力学控制反应。对浊度数据的Arrhenius分析表明,两个动力学相E_a = 53±7 kcal / mol,分别对应于通过电子显微镜观察到的形态学转变。一个过渡涉及VLDL融合,部分破裂和球形小颗粒(d = 7-15 nm)的解离,另一个过渡涉及脂蛋白的完全分解和脂质聚结成液滴,伴随载脂蛋白B的解离。 VLDL变性的大小和密度与高密度脂蛋白(HDL)相当;它们具有非极性脂质核心和极性表面,该表面由可交换的载脂蛋白(E和可能的Cs)和磷脂组成。我们得出的结论是,类似于HDL和LDL,VLDL通过动力学屏障得以稳定,该动力学屏障可防止颗粒融合和破裂,并降低脂蛋白类和亚类之间的自发相互转换。除融合外,VLDL破坏还涉及瞬时形成的HDL样颗粒,可模仿血浆中VLDL和HDL库之间的蛋白质交换。

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