PACKING OF CHOLESTEROL MOLECULES IN HUMAN LOW-DENSITY-LIPOPROTEIN
PACKING OF CHOLESTEROL MOLECULES IN HUMAN LOW-DENSITY-LIPOPROTEIN
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DOI：
10.1021/bi00355a016
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发表时间：
1986-04-08
期刊：
影响因子：
2.9
通讯作者：
PHILLIPS, MC
中科院分区：
文献类型：
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作者：
LUNDKATZ, S;PHILLIPS, MC
人低密度脂蛋白(LDL)的高分辨率、质子去耦合的13C核磁共振波谱(90.55 MHz)被用来研究该颗粒中未酯化胆固醇分子的物理状态。大约一半的低密度脂蛋白中的胆固醇分子被来自Celite的[4-13C]胆固醇所取代。大约三分之二的胆固醇分子在德尔塔引起了共振。来自C-4原子的41.8。这个信号被指定给位于低密度脂蛋白颗粒表面的与磷脂分子混合的单层中的胆固醇分子；这种胆固醇分子的C-4核的自旋晶格弛豫因水相中Mn2+的存在而增强。剩下的三分之一的胆固醇分子显然既不与磷脂相关，也不暴露在水相中；这些胆固醇分子被推定位于颗粒的核心。这两种微环境中的胆固醇分子在核磁共振时间尺度上交换较慢，但在生物时间尺度上交换较快，因此低密度脂蛋白中的胆固醇分子在生理上表现为一个池。在低密度脂蛋白光谱中，磷脂酰胆碱和鞘磷脂分子的N(CH3)3共振强度损失了约20%，这是由于载脂蛋白B存在于低密度脂蛋白颗粒表面，它可能固定了一些磷脂极性基团。自旋晶格驰豫时间的测量表明，胆固醇分子在低密度脂蛋白(LDL)表面的快速轴向运动与高密度脂蛋白(HDL)中的相同。然而，比较低密度脂蛋白和高密度脂蛋白表面分子的[4-13C]胆固醇共振的线宽表明，胆固醇的振荡运动在低密度脂蛋白表面较慢和/或更受限制。这可能有三个原因：(1)与高密度脂蛋白相比，低密度脂蛋白中磷脂酰胆碱的酰链饱和度更高；(2)前一种脂蛋白中鞘磷脂/磷脂酰胆碱的比值更高；(3)与高密度脂蛋白相比，低密度脂蛋白表面的未酯化胆固醇/磷脂摩尔比更高。与高密度脂蛋白相比，低密度脂蛋白与高密度脂蛋白的胆固醇交换速率相对较慢，这归因于低密度脂蛋白表面磷脂/胆固醇单层的紧密堆积。
High-resolution, proton-decoupled 13C nuclear magnetic resonance spectra (90.55 MHz) of human low-density lipoprotein (LDL) have been employed to investigate the physical state of unesterified cholesterol molecules in this particle. Approximately half of the cholesterol molecules in LDL were replaced with [4-13C]cholesterol by exchange from Celite. About two-thirds of the cholesterol molecules contribute to a resonance at .delta. 41.8 from the C-4 atom. This signal is assigned to cholesterol molecules located at the surface of the LDL particle in a mixed monolayer with phospholipid molecules; the spin-lattice relaxation of the C-4 nucleus of such cholesterol molecules is enhanced by the presence of Mn2+ ions in the aqueous phase. The remaining one-third of the cholesterol molecules are apparently neither associated with phospholipid nor exposed to the aqueous phase; these cholesterol molecules are presumed to be located in the core of the particle. Cholesterol molecules in the two microenvironments are in slow exchange on the NMR time scale but in fast exchange on a biological time scale, so that the cholesterol molecules in LDL behave physiologically as one pool. There is a loss of about 20% of the intensity of the N(CH3)3 resonance from phosphatidylcholine and sphingomyelin molecules in the LDL spectrum; this is attributed to the presence of apolipoprotein B in the surface of LDL particles, which may immobilize some of the phospholipid polar groups. Spin-lattice relaxation time measurements suggest that the fast axial motions of cholesterol molecules in the surface of LDL are the same as in high-density lipoprotein (HDL). However, comparison of the line widths of the [4-13C]cholestrol resonance from molecules in the surfaces of LDL and HDL suggests that the cholesterol oscillatory motions are slower and/or more restricted in the surface of LDL. There are probably three contributions to this effect: (1) the greater acyl chain saturation of the phosphatidylcholine in LDL compared to that in HDL, (2) the higher sphingomyelin/phosphatidylcholine ratio in the former lipoprotein, and (3) the higher unesterified cholesterol/phospholipid molar ratio in the surface of LDL compared to that in HDL. The relatively slow rate of exchange of cholesterol from LDL compared to that from HDL is attributed to the tighter packing of the phospholipid/cholesterol monolayer in the surface of LDL.