The metabolism of low density lipoprotein in familial type II hyperlipoproteinemia.
The metabolism of low density lipoprotein in familial type II hyperlipoproteinemia.
复制标题
家族性II型高脂蛋白血症中低密度脂蛋白的代谢。
DOI：
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发表时间：
1972
影响因子：
15.9
通讯作者：
R. Levy
中科院分区：
文献类型：
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作者：
T. Langer;W. Strober;R. Levy
使用纯化的放射性碘标记的 LDL，对 10 名正常人和 10 名家族性 II 型高脂蛋白血症患者的低密度脂蛋白（LDL、β 脂蛋白）代谢进行了研究。超过 97% 的标签与 LDL 的蛋白质部分结合，因此周转数据反映了 LDL-脱辅基蛋白的命运和分布。比较生物筛选和未筛选的标记 LDL 制剂在狗体内的代谢行为，以及对人类标记 LDL 降解产生的放射性碘化物尿液排泄的分析表明，分离、纯化和标记技术没有导致明显的变性。正常人的 LDL 胆固醇血浆浓度为 105+/-21 mg/100 ml（平均值+/-1 SD），而 II 型高脂蛋白血症患者的血浆浓度为 254+/-47 mg/100 mg；这些值分别对应于 63+/-13 mg/100 ml 和 153+/-30 mg/100 ml 的 LDL-脱辅基蛋白浓度。尽管浓度存在这些差异，两组中 LDL-脱辅基蛋白的合成率并无显着差异（正常人群为每天 14.43+/-1.75 mg/kg，II 型人群为每天 15.01+/-1.71 mg/kg），血管内空间中总可交换 LDL 的比例也没有任何差异（68.4+/-4.3% 对比 73.3+/-5.2%）。然而，正常人的LDL分解代谢率与II型高脂蛋白血症患者存在显着差异（正常人为0.462+/-0.077/天，II型为0.237+/-0.044/天），相应地，LDL的生物半衰期也显着延长（正常人为3.08+/-0.35天，II型为4.68+/-0.44天）。这些数据表明，本文研究的 II 型高脂蛋白血症个体血浆 LDL 浓度的病理性升高是由于 LDL 降解分数率降低，而不是由于 LDL 合成异常。这种分解代谢缺陷可能是 II 型高脂蛋白血症的主要缺陷，或者可能继发于脂质代谢的潜在异常。
The metabolism of low density lipoprotein (LDL, beta lipoprotein) was studied in 10 normal individuals and 10 patients with familial type II hyperlipoproteinemia using purified radioiodinated LDL. Over 97% of the label was bound to the protein moiety of LDL and therefore the turnover data reflect the fate and distribution of LDL-apoprotein. Comparison of the metabolic behavior of biologically screened and unscreened labeled LDL preparations in dogs as well as the analysis of the urinary excretion of radioiodide derived from labeled LDL degradation in humans indicated that no significant denaturation resulted from the isolation, purification, and labeling techniques. The plasma concentration of LDL-cholesterol in normals was 105+/-21 mg/100 ml (mean +/-1 SD) in contrast to 254+/-47 mg/100 mg in patients with type II hyperlipoproteinemia; these values corresponded to LDL-apoprotein concentrations of 63+/-13 mg/100 ml and 153+/-30 mg/100 ml, respectively. Despite these differences in concentration, the synthetic rate of LDL-apoprotein in both groups was not significantly different (14.43+/-1.75 mg/kg per day in normals vs. 15.01+/-1.71 mg/kg per day in type II) nor was there any difference in the fraction of the total exchangeable LDL which was in the intravascular space (68.4+/-4.3% vs. 73.3+/-5.2%). However, the fractional catabolic rate of LDL in normal individuals differed significantly from that of patients with type II hyperlipoproteinemia (0.462+/-0.077/day in normals vs. 0.237+/-0.044/day in type II) and correspondingly the biological half-life of LDL was significantly prolonged (3.08+/-0.35 days normals vs. 4.68+/-0.44 days in type II). These data indicate that the pathologic elevation of plasma LDL concentration in the individuals with type II hyperlipoproteinemia studied here is due to a decreased fractional rate of LDL degradation rather than to an abnormality of LDL synthesis. This defect of catabolism may be the primary defect in type II hyperlipoproteinemia or, alternatively, may be secondary to an underlying abnormality in lipid metabolism.