Physicochemical properties of apolipoprotein(a) and lipoprotein(a-) derived from the dissociation of human plasma lipoprotein (a).
Physicochemical properties of apolipoprotein(a) and lipoprotein(a-) derived from the dissociation of human plasma lipoprotein (a).
复制标题
DOI：
--
复制
发表时间：
1986-07
期刊：
影响因子：
--
通讯作者：
G. Fless;M. E. ZumMallen;A. Scanu
中科院分区：
文献类型：
--
作者：
G. Fless;M. E. ZumMallen;A. Scanu
人血浆脂蛋白(A)(Lp(A))的化学还原得到两种水溶性产物，经速率区带超速离心法分离。载脂蛋白(A)(apo(A))从梯度的底部完全回收，而含有Lp(A)的所有脂类和apo-B100的脂蛋白(a-)(Lp(a-))漂浮。经圆二色谱和粘度计测定，Lp(a-)与低密度脂蛋白(LDL)一致。Lp(a-)的质量比自体低密度脂蛋白略大，并且含有比例更多的甘油三酯。Lp(A)和Lp(a-)之间的质量差异是由于Lp(A)粒子损失了2个apo(A)分子。通过在6M盐酸胍中的沉淀平衡测定，还原和羧甲基化apo(A)的相对分子质量为281,000。经圆二色谱分析，apo(A)的结构大多为无规结构(71%)，其余为8%的α-螺旋和21%的β-折叠，其特性粘度为28.3cm~3/g，与扩展的柔性线圈一致。氨基酸组成的特点是含有异常高的脯氨酸(11.4摩尔%)以及色氨酸、酪氨酸、精氨酸、苏氨酸，以及少量的赖氨酸、苯丙氨酸和异亮氨酸。Apo(A)含有28.1%的碳水化合物，甘露糖、半乳糖、氨基半乳糖、氨基葡萄糖和唾液酸的摩尔比约为3：7：5：4：7。总体而言，Lp(A)的结构似乎与坚硬的球形低密度脂蛋白类似的核心颗粒一致，由于其与诸如apo(A)等柔性糖蛋白的结合，有利于捕获大量的流体动力学相关溶剂。此外，从Lp(A)中去除apo(A)所产生的Lp(a-)残基在结构上与自体低密度脂蛋白相似，但不完全相同。
Chemical reduction of human plasma lipoprotein(a) (Lp(a)) yielded two water-soluble products which were separated by rate zonal ultracentrifugation. Apolipoprotein(a) (apo(a)) was completely recovered from the bottom of the gradient, whereas lipoprotein(a-) (Lp(a-)), which contained all of the lipids and apo-B100 of Lp(a), floated. By the techniques of circular dichroism and viscometry Lp(a-) was identical to low density lipoprotein (LDL). Lp(a-) was slightly larger in mass than autologous LDL and contained proportionally more triglyceride. The difference in mass between Lp(a) and Lp(a-) was accounted for by the loss of 2 molecules of apo(a) from the Lp(a) particle. The molecular weight of reduced and carboxymethylated apo(a) was 281,000 as determined by sedimentation equilibrium in 6 M guanidine HCl. By circular dichroism the structure of apo(a) was mostly random (71%) with the remainder representing 8% alpha-helix and 21% beta-sheet; its intrinsic viscosity, 28.3 cm3/g, was consistent with an extended flexible coil. The amino acid composition was characterized by an unusually high content of proline (11.4 mol %) as well as tryptophan, tyrosine, arginine, threonine, and a low amount of lysine, phenylalanine, and isoleucine. Apo(a) contained 28.1% carbohydrate by weight represented by mannose, galactose, galactosamine, glucosamine, and sialic acid in an approximate molar ratio of 3:7:5:4:7, respectively. Overall, the structure of Lp(a) appears to be consistent with a rigid spherical LDL-like core particle which, as a consequence of its association with a flexible glycoprotein such as apo(a), favors the entrapment of significant amounts of hydrodynamically associated solvent. Furthermore, the Lp(a-) remnant generated by the removal of apo(a) from Lp(a) was similar in structure but not identical to autologous LDL.