Nichols A V, Gong E L, Blanche P J, Forte T M, Shore V G
J Lipid Res. 1987 Jun;28(6):719-32.
The lecithin:cholesterol acyltransferase (LCAT)-induced transformation of two discrete species of model complexes that differ in number of apolipoprotein A-I (apoA-I) molecules per particle was investigated. One complex species (designated 3A-I(UC)-complexes) contained 3 apoA-I per particle, was discoidal (13.5 X 4.4 nm), and had a molar composition of 22:78:1 (unesterified cholesterol (UC):egg yolk phosphatidylcholine (egg yolk PC):apoA-I). The other complex species (designated 2A-I(UC)complexes) containing 2 apoA-I per particle was also discoidal (8.4 X 4.1 nm) and had a molar composition of 6:40:1. Transformation of 3A-I(UC)complexes by partially purified LCAT yielded a product (24 hr, 37 degrees C) with a cholesteryl ester (CE) core, 3 apoA-I, and a mean diameter of 9.2 nm. The 2A-I(UC)complexes were only partially transformed to a core-containing product (24 hr, 37 degrees C) which also had 3 apoA-I; this product, however, was smaller (diameter of 8.5 nm) than the product from 3A-I(UC)complexes. Transformation of 3A-I(UC)complexes appeared to result from build-up of core CE directly within the precursor complex. Transformation of 2A-I(UC)complexes, however, followed a stepwise pathway to the product with 3 apoA-I, apparently involving fusion of transforming precursors and release of one apoA-I from the fusion product. In the presence of low density lipoprotein (LDL), used as a source of additional cholesterol, conversion of 2A-I(UC)complexes to the product with 3 apoA-I was more extensive. The transformation product of 3A-I(UC)complexes in the presence of LDL also had 3 apoA-I but was considerably smaller in size (8.6 vs. 9.2 nm, diameter) and had a twofold lower molar content of PC compared with the product formed without LDL. LDL appeared to act both as a donor of UC and an acceptor of PC. Transformation products with 3 apoA-I obtained under the various experimental conditions in the present studies appear to be constrained in core CE content (between 13 to 22 CE per apoA-I; range of 9 CE molecules) but relatively flexible in content of surface PC molecules they can accommodate (between 24 to 49 PC per apoA-I; range of 25 PC molecules). The properties of the core-containing products with 3 apoA-I compare closely with those of the major subpopulation of human plasma HDL in the size range of 8.2-8.8 nm that contains the molecular weight equivalent of 3 apoA-I molecules.
研究了卵磷脂胆固醇酰基转移酶（LCAT）诱导的两种离散模型复合物的转化，这两种复合物每个颗粒中载脂蛋白A-I（apoA-I）分子的数量不同。一种复合物（称为3A-I(UC)复合物）每个颗粒含有3个apoA-I，呈盘状（13.5×4.4纳米），摩尔组成为22:78:1（游离胆固醇（UC）：蛋黄磷脂酰胆碱（蛋黄PC）：apoA-I）。另一种复合物（称为2A-I(UC)复合物）每个颗粒含有2个apoA-I，也呈盘状（8.4×4.1纳米），摩尔组成为6:40:1。部分纯化的LCAT对3A-I(UC)复合物的转化产生了一种产物（24小时，37℃），该产物具有胆固醇酯（CE）核心、3个apoA-I，平均直径为9.2纳米。2A-I(UC)复合物仅部分转化为含核心的产物（24小时，37℃），该产物也有3个apoA-I；然而，该产物比3A-I(UC)复合物产生的产物小（直径8.5纳米）。3A-I(UC)复合物的转化似乎是由于核心CE直接在前体复合物内积累所致。然而，2A-I(UC)复合物的转化遵循一条逐步形成含3个apoA-I产物的途径，显然涉及转化前体的融合以及一个apoA-I从融合产物中释放。在用作额外胆固醇来源的低密度脂蛋白（LDL）存在下，2A-I(UC)复合物向含3个apoA-I产物的转化更为广泛。在LDL存在下3A-I(UC)复合物的转化产物也有3个apoA-I，但尺寸明显较小（直径8.6对9.2纳米），与无LDL时形成的产物相比，PC的摩尔含量降低了两倍。LDL似乎既作为UC的供体又作为PC的受体。在本研究的各种实验条件下获得的含3个apoA-I的转化产物似乎在核心CE含量方面受到限制（每个apoA-I含13至22个CE；范围为9个CE分子），但在它们能容纳的表面PC分子含量方面相对灵活（每个apoA-I含24至49个PC；范围为25个PC分子）。含3个apoA-I的含核心产物的性质与分子量相当于3个apoA-I分子的8.2 - 8.8纳米大小范围内的人血浆HDL主要亚群的性质密切相关。
