CARBAMYLATION-INDUCED ALTERATIONS IN LOW-DENSITY-LIPOPROTEIN METABOLISM
CARBAMYLATION-INDUCED ALTERATIONS IN LOW-DENSITY-LIPOPROTEIN METABOLISM
复制标题
DOI：
10.1038/ki.1992.179
复制
发表时间：
1992-05-01
影响因子：
19.6
通讯作者：
KESANIEMI, YA
中科院分区：
文献类型：
--
作者：
HORKKO, S;SAVOLAINEN, MJ;KESANIEMI, YA
低密度脂蛋白是通过在氰酸钾 (KCNO) 中孵育 LDL，从氨甲酰 (carbamyl-LDL) 衍生而来。 氨甲酰-LDL 中游离氨基的比例与氰酸钾中的孵育时间（范围为 5 至 360 分钟）呈负相关（r = -0.95）。 氨甲酰化不会改变 LDL 颗粒的化学成分或浮选特性。 然而，氨甲酰-LDL 的电泳迁移率随着氨甲酰化程度的增加而明显增加。 与对照 LDL 相比，氨甲酰 LDL 与牛肾上腺皮质膜 LDL apoB/E 受体的结合显着降低。 当只有 9% 的游离氨基源自氨甲酰时，已经观察到结合减少。 LDL 的轻微氨甲酰化（少于 20% 的游离氨基）会降低兔血浆中 LDL 的体内清除率。 然而，当产生超过 20% 的游离氨基时，与对照 LDL 相比，氨甲酰 LDL 的清除速度加快。 从尿毒症患者中分离出的低密度脂蛋白在兔子体内的清除速度比从对照受试者中分离出的低密度脂蛋白要慢。 如本研究中观察到的，假设 LDL 的氨甲酰化也可能在体内发生，导致 LDL 与 LDL B/E 受体结合的类似改变，那么尿毒症相关的加速动脉粥样硬化可能有另一种机制解释。
Low-density lipoprotein was derived from carbamyl (carbamyl-LDL) by incubating LDL in potassium cyanate (KCNO). The proportion of free amino groups in the carbamyl-LDL was negatively correlated (r = -0.95) with the time of incubation in potassium cyanate (ranged from 5 to 360 min). The carbamylation did not change the chemical composition or the flotation characteristics of the LDL particles. However, the electrophoretic mobility of carbamyl-LDL was distinctly increased with the extent of carbamylation. The carbamyl-LDL had substantially decreased binding to the LDL apoB/E receptors of the bovine adrenocortical membranes when compared to the control-LDL. The reduced binding was already observed when only 9% of the free amino groups were derived from carbamyl. A minor carbamylation of LDL (less than 20% of the free amino groups) decreased the in vivo clearance of LDL from rabbit plasma. However, when more than 20% of the free amino groups were derived the carbamyl-LDL had accelerated clearance compared to the control-LDL. LDL isolated from uremic patients was cleared in rabbits at a slower rate than LDL isolated from a control subject. Providing that carbamylation of LDL could also occur in vivo resulting in similar alterations of the LDL binding to the LDL B/E receptors, as observed in the present study, the uremia-related accelerated atherosclerosis could have one additional mechanistic explanation.