Drayna D, Jarnagin A S, McLean J, Henzel W, Kohr W, Fielding C, Lawn R
Nature. 1987;327(6123):632-4. doi: 10.1038/327632a0.
The transfer of insoluble cholesteryl esters among lipoprotein particles is a vital step in normal cholesterol homeostasis and may be involved in the development of atherosclerosis. Extrahepatic tissues lack the enzymes required for the degradation of sterols to the excretable form of bile acids. Cholesterol synthesized in these tissues in excess of that needed for the synthesis of cell membranes or steroid hormones must accordingly be returned through the plasma to the liver for catabolism. The series of reactions involved has been termed reverse cholesterol transport. Catalysed steps of this pathway are believed to include an efflux from peripheral cells, which generates a diffusion gradient between these membranes and extracellular fluid; esterification of this cholesterol by lecithin-cholesterol acyltransferase (LCAT) (phosphatidylcholine-sterol acyltransferase) acting on species of high-density lipoproteins; transfer of the cholesteryl esters formed (largely to low- and very low-density lipoproteins) (LDL and VLDL) by a cholesteryl ester transfer protein (CETP); and removal of these lipoproteins, together with their cholesteryl ester content, by the liver through receptor-mediated and nonspecific endocytosis. Of these steps, the CETP reaction is the least characterized. Several laboratories have reported the purification from human plasma of proteins active on cholesteryl ester transfer between lipoprotein particles and possibly between cells and plasma. However, the reported relative molecular mass (Mr), abundance and specificity of the purified activities have differed considerably. We have recently described the preparation of a highly active CETP of Mr 74,000 purified about 100,000-fold from human plasma, which may represent the functional component of earlier preparations. Using a partial amino-acid sequence from this purified protein, CETP complementary DNA derived from human liver DNA has been cloned and sequenced and the cloned DNA used to detect CETP messenger RNA in a number of human tissues.
不溶性胆固醇酯在脂蛋白颗粒之间的转移是正常胆固醇稳态中的关键步骤，可能与动脉粥样硬化的发展有关。肝外组织缺乏将固醇降解为可排泄胆汁酸形式所需的酶。因此，这些组织中合成的胆固醇若超过细胞膜或类固醇激素合成所需量，必须通过血浆返回肝脏进行分解代谢。所涉及的一系列反应被称为逆向胆固醇转运。据信该途径的催化步骤包括从外周细胞流出，这在这些细胞膜和细胞外液之间产生扩散梯度；高密度脂蛋白上的卵磷脂 - 胆固醇酰基转移酶（LCAT）（磷脂酰胆碱 - 固醇酰基转移酶）将这种胆固醇酯化；胆固醇酯转移蛋白（CETP）将形成的胆固醇酯（主要转移到低密度和极低密度脂蛋白）（LDL和VLDL）进行转移；以及肝脏通过受体介导的和非特异性内吞作用清除这些脂蛋白及其胆固醇酯含量。在这些步骤中，CETP反应的特征最少。几个实验室报告了从人血浆中纯化出的对脂蛋白颗粒之间以及可能在细胞和血浆之间的胆固醇酯转移有活性的蛋白质。然而，所报道的纯化活性的相对分子质量（Mr）、丰度和特异性差异很大。我们最近描述了一种Mr为74,000的高活性CETP的制备，该CETP从人血浆中纯化了约100,000倍，可能代表早期制备物的功能成分。利用该纯化蛋白的部分氨基酸序列，已克隆并测序了源自人肝脏DNA的CETP互补DNA，并使用克隆的DNA检测了多种人体组织中的CETP信使RNA。
