Musliner T A, Long M D, Forte T M, Nichols A V, Gong E L, Blanche P J, Krauss R M
Research Medicine and Radiation Biophysics Division, University of California, Berkeley 94720.
J Lipid Res. 1991 Jun;32(6):917-33.
Incubation of low (LDL), intermediate (IDL), or very low density lipoproteins (VLDL) with palmitic acid and either high density lipoproteins (HDL), delipidated HDL, or purified apolipoprotein (apo) A-I resulted in the formation of lipoprotein particles with discoidal structure and mean particle diameters ranging from 146 to 254 A by electron microscopy. Discs produced from IDL or LDL averaged 26% protein, 42% phospholipid, 5% cholesteryl esters, 24% free cholesterol, and 3% triglycerides; preparations derived from VLDL contained up to 21% triglycerides. ApoA-I was the predominant protein present, with smaller amounts of apoA-II. Crosslinking studies of discs derived from LDL or IDL indicated the presence of four apoA-I molecules per particle, while those derived from large VLDL varied more in size and contained as many as six apoA-I molecules per particle. Incubation of discs derived from IDL or LDL with purified lecithin:cholesterol acyltransferase (LCAT), albumin, and a source of free cholesterol produced core-containing particles with size and composition similar to HDL2b. VLDL-derived discs behaved similarly, although the HDL products were somewhat larger and more variable in size. When discs were incubated with plasma d greater than 1.21 g/ml fraction rather than LCAT, core-containing particles in the size range of normal HDL2a and HDL3a were also produced. A variety of other purified free fatty acids were shown to promote disc formation. In addition, some mono and polyunsaturated fatty acids facilitated the formation of smaller, spherical particles in the size range of HDL3c. Both discoidal and small spherical apoA-I-containing lipoproteins were generated when native VLDL was incubated with lipoprotein lipase in the presence of delipidated HDL. We conclude that lipolysis product-mediated dissociation of lipid-apoA-I complexes from VLDL, IDL, or LDL may be a mechanism for formation of HDL subclasses during lipolysis, and that the availability of different lipids may influence the type of HDL-precursors formed by this mechanism.
将低密度脂蛋白(LDL)、中间密度脂蛋白(IDL)或极低密度脂蛋白(VLDL)与棕榈酸以及高密度脂蛋白(HDL)、脱脂HDL或纯化的载脂蛋白(apo)A-I一起孵育,通过电子显微镜观察发现形成了具有盘状结构且平均粒径在146至254埃之间的脂蛋白颗粒。由IDL或LDL产生的圆盘状颗粒平均含有26%的蛋白质、42%的磷脂、5%的胆固醇酯、24%的游离胆固醇和3%的甘油三酯;源自VLDL的制剂含有高达21%的甘油三酯。ApoA-I是主要存在的蛋白质,还有少量的apoA-II。对源自LDL或IDL的圆盘状颗粒的交联研究表明,每个颗粒存在四个apoA-I分子,而源自大的VLDL的颗粒大小变化更大,每个颗粒含有多达六个apoA-I分子。将源自IDL或LDL的圆盘状颗粒与纯化的卵磷脂:胆固醇酰基转移酶(LCAT)、白蛋白和游离胆固醇来源一起孵育,产生了大小和组成与HDL2b相似的含核心颗粒。源自VLDL的圆盘状颗粒表现类似,尽管产生的HDL产物稍大且大小变化更大。当将圆盘状颗粒与血浆密度大于1.21 g/ml的部分而非LCAT一起孵育时,也会产生正常HDL2a和HDL3a大小范围内的含核心颗粒。多种其他纯化的游离脂肪酸也被证明可促进圆盘状颗粒的形成。此外,一些单不饱和脂肪酸和多不饱和脂肪酸有助于形成HDL3c大小范围内的较小球形颗粒。当天然VLDL在脱脂HDL存在下与脂蛋白脂肪酶一起孵育时,会产生盘状和含apoA-I的小球形脂蛋白。我们得出结论,脂解产物介导的脂质-apoA-I复合物从VLDL、IDL或LDL的解离可能是脂解过程中HDL亚类形成的一种机制,并且不同脂质的可用性可能会影响通过该机制形成的HDL前体的类型。
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