KINETICS AND MECHANISM OF FREE-CHOLESTEROL EXCHANGE BETWEEN HUMAN-SERUM HIGH-DENSITY AND LOW-DENSITY LIPOPROTEINS
KINETICS AND MECHANISM OF FREE-CHOLESTEROL EXCHANGE BETWEEN HUMAN-SERUM HIGH-DENSITY AND LOW-DENSITY LIPOPROTEINS
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DOI：
10.1021/bi00541a025
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发表时间：
1982-01-01
期刊：
影响因子：
2.9
通讯作者：
PHILLIPS, MC
中科院分区：
文献类型：
--
作者：
LUNDKATZ, S;HAMMERSCHLAG, B;PHILLIPS, MC
本文通过追踪胆固醇和磷脂酰胆碱在高密度脂蛋白（HDL）和低密度脂蛋白（LDL）之间的转移，研究了胆固醇和磷脂酰胆碱（PC）在人血清脂蛋白之间的交换机制。最初，[14 C]胆固醇存在于供体脂蛋白颗粒中，其为HDL 2、HDL 3或LDL。在盐水溶液中孵育不同时间后，通过用Mn 2 +-肝素试剂沉淀LDL来分离HDL和LDL。供体HDL 3中超过90%的[14 C]胆固醇在一级过程中转移为LDL，其半衰期在37 ℃下为2.9分钟。C.这表明，胆固醇分子从HDL的胆固醇酯/甘油三酯核心转移到颗粒表面的磷脂/脱辅基蛋白单层对交换没有速率限制。从HDL 3到LDL的二棕榈酰-PC交换的半衰期为5 ± 1。1 h，表明PC的通量远低于胆固醇。37 ° C下[14 C]胆固醇从HDL 2和LDL交换的半衰期C分别为4和45 min。在37 ° C下的界面通量。对于LDL、HDL 2和HDL 3，来自各种脂蛋白的C分别为4、15和10个胆固醇分子/（10 nm 2 h）。当LDL受体浓度增加40倍时，标记胆固醇从HDL 3转移的速率不受影响。胆固醇转移的活化能在4 ° C和37 ° C之间。HDL 3、HDL 2和LDL的C为70 ±。3，75 .+-. 78 .第78章+。3 kJ/mol。胆固醇在脂蛋白之间交换过程的一般特征类似于小单层囊泡之间的交换过程。结果仅与胆固醇分子通过水相扩散的交换机制一致;实验活化能与脂质从供体脂蛋白解吸到水相中相关。
The mechanism of cholesterol and phosphatidylcholine (PC) exchange between human serum lipoproteins was investigated by following the transfer of radiolabeled cholesterol and PC between high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Initially, [14C]cholesterol was present in the donor lipoprotein particle which was either HDL2, HDL3, or LDL. After incubation in saline solution for various times, the HDL and LDL were separated by precipitation of the LDL with Mn2+-heparin reagent. More than 90% of the [14C]cholesterol in donor HDL3 is transferred to LDL in a first-order process whose half-time is 2.9 min at 37.degree. C. This indicates that transfer of cholesterol molecules from the cholesterol ester/triglyceride core of HDL to the phospholipid/apoprotein monolayer at the surface of the particle is not rate limiting for exchange. The half-time for dipalmitoyl-PC exchange from HDL3 to LDL is 5 .+-. 1 h, indicating that the flux of PC is much lower than that of cholesterol. The half-times for [14C]cholesterol exchange from HDL2 and LDL at 37.degree. C are 4 and 45 min, respectively. The interfacial fluxes at 37.degree. C from the various lipoproteins are 4, 15, and 10 cholesterol molecules/(10 nm2 h), respectively, for LDL, HDL2, and HDL3. The rate of labeled cholesterol transfer from HDL3 is not affected when the concentration of LDL acceptor is increased 40-fold. The activation energies of cholesterol transfer between 4 and 37.degree. C for HDL3, HDL2, and LDL are 70 .+-. 3, 75 .+-. 3, and 78 .+-. 3 kJ/mol, respectively. The general characteristics of the process of exchange of cholesterol between lipoproteins resemble those for exchange between small unilamellar vesicles. The results are only consistent with a mechanism of exchange in which cholesterol molecules diffuse through the aqueous phase; the experimental activation energy is associated with desorption of lipid from the donor lipoprotein into the aqueous phase.