RECEPTOR-MEDIATED CATABOLISM OF LOW-DENSITY LIPOPROTEIN IN MAN - QUANTITATION USING GLUCOSYLATED LOW-DENSITY LIPOPROTEIN
RECEPTOR-MEDIATED CATABOLISM OF LOW-DENSITY LIPOPROTEIN IN MAN - QUANTITATION USING GLUCOSYLATED LOW-DENSITY LIPOPROTEIN
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DOI：
10.1172/jci110849
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发表时间：
1983-01-01
影响因子：
15.9
通讯作者：
STEINBRECHER, UP
中科院分区：
文献类型：
--
作者：
KESANIEMI, YA;WITZTUM, JL;STEINBRECHER, UP
低密度脂蛋白 (LDL) 分解代谢通过 LDL 受体依赖性和 LDL 受体非依赖性途径发生。在氰基硼氢化物存在下，LDL 的非酶促糖基化不可逆地阻断 LDL 的赖氨酸残基。糖化低密度脂蛋白（GLC-LDL）不被成纤维细胞的低密度脂蛋白受体降解，其被巨噬细胞的降解与天然低密度脂蛋白相似。 GLC-LDL可能是LDL受体独立分解代谢的良好示踪剂，如果与总LDL分解代谢示踪剂结合，应该可以计算LDL受体依赖性分解代谢的程度。为了确定每个途径对人类的贡献，制备了 125I-GLC-LDL 和 131I-对照 LDL，并同时测定了 4 名受试者中每种示踪剂的分解代谢率 (FCR)。在初步实验中，糖基化的条件不影响低密度脂蛋白的周转。在 4 名受试者中，总 LDL 分解代谢的 FCR 范围为 0.345-0.724 d-1，平均值为 0.57 .+-。 0.16d-1。 GLC-LDL 的 FCR 范围为 0.071 至 0.141 d-1，平均值为 0.11 .+-。 0.03d-1。后者与纯合子家族性高胆固醇血症受试者中报道的天然 LDL 的 FCR 相似，支持 GLC-LDL 仅追踪受体独立途径的解释。尽管这些受试者的总 LDL 分解代谢范围很广，但 LDL 受体独立的分解代谢仅占总分解代谢的 19.5-20.6%。反过来，LDL 受体依赖性分解代谢占每个人总清除率的 80%。此外，虽然 LDL 的衰减曲线显示出通常的双相模式，但即使跟踪长达 48 天，每个受试者的 GLC-LDL 衰减曲线也是单指数的。显然，LDL 受体活性是造成 LDL 衰减双相性质的原因。这些研究强调了 LDL 受体活性在人类正常 LDL 代谢中的核心作用。 [讨论了 LDL 在动脉粥样硬化发展中的作用。]
Low density lipoprotein (LDL) catabolism occurs by LDL receptor-dependent and LDL receptor-independent pathways. Nonenzymatic glucosylation of LDL in the presence of cyanoborohydride irreversibly blocks the lysine residues of LDL. Glucosylated LDL (GLC-LDL) was not degraded by the LDL receptor of fibroblasts, and its degradation by macrophages was similar to that of native LDL. GLC-LDL may be a good tracer of LDL receptor-independent catabolism, and if combined with a tracer of total LDL catabolism, should allow the calculation of the extent of LDL receptor-dependent catabolism. To determine the contribution of each pathway in man, 125I-GLC-LDL and 131I-control LDL were prepared and the fractional catabolic rate (FCR) of each tracer in 4 subjects simultaneously determined. In preliminary experiments, the conditions for glucosylation did not affect LDL turnover. In the 4 subjects, the FCR for total LDL catabolism ranged from 0.345-0.724 d-1 with a mean of 0.57 .+-. 0.16 d-1. The FCR of GLC-LDL varied from 0.071 to 0.141 d-1 with a mean of 0.11 .+-. 0.03 d-1. The latter is similar to the FCR reported for native LDL in subjects with homozygous familial hypercholesterolemia, supporting the interpretation that GLC-LDL traces only the receptor-independent pathway. Despite the wide range of total LDL catabolism in these subjects, LDL receptor-independent catabolism acccounted for only 19.5-20.6% of total catabolism. In turn, LDL receptor-dependent catabolism accounted for 80% of total clearance in each person. Furthermore, while the decay curve of LDL showed the usual biphasic pattern, the decay curve of GLC-LDL was monoexponential in each subject even when followed for as long as 48 d. Apparently, LDL receptor activity is responsible for the biphasic nature of LDL decay. These studies emphasize the central role of LDL receptor activity in normal LDL metabolism in man. [The involvement of LDL in the development of atherosclerosis is discussed.].