Hoeg J M, Demosky S J, Lackner K J, Osborne J C, Oliver C, Brewer H B
Biochim Biophys Acta. 1986 Mar 21;876(1):13-21. doi: 10.1016/0005-2760(86)90312-7.
The role of the cellular receptor for the low-density lipoproteins (LDL) in cholesterol transport was initially defined through the study of nonhepatic cells in vitro. Since the liver is central in plasma lipoprotein metabolism, an investigation of hepatic lipoprotein receptors is important for understanding normal lipoprotein transport. Utilizing human hepatic and fibroblast membranes, the characteristics of receptors for LDL from hepatic and nonhepatic tissues were directly compared. Human hepatic membranes reversibly bound LDL within 5 min. Although both fibroblast and hepatic membranes saturably bound LDL at 37 degrees C, the fibroblast LDL receptor affinity (Kd = 2.5 X 10(-8) M) and number (5.5 X 10(12) sites/mg membrane protein) were greater than the hepatic receptor affinity (Kd = 10.8 X 10(-8) M) and number (0.5 X 10(12) sites/mg membrane protein). In contrast to the fibroblast LDL receptor which was unable to bind LDL in the presence of EDTA, the hepatic LDL receptor binding of LDL was only partially blocked by EDTA. The binding of LDL to its hepatic receptor is highly temperature-dependent, and studies utilizing both radiolabeled LDL and colloidal gold-labeled LDL indicate that little, if any, binding of LDL hepatic membranes occur at 0-4 degrees C. The hepatic membrane receptor(s) (Mr approximately equal to 270 000 and 330 000) differ from that of the fibroblast LDL receptor (Mr approximately equal to 130 000) and these proteins are present in hepatic membranes from a patient lacking the fibroblast LDL receptor. These data indicate that an expressed hepatic LDL receptor has unique properties different from those of the fibroblast LDL receptor and that the expressed protein(s) is genetically distinct from the fibroblast receptor.
低密度脂蛋白（LDL）细胞受体在胆固醇转运中的作用最初是通过体外对非肝细胞的研究来确定的。由于肝脏在血浆脂蛋白代谢中起核心作用，因此研究肝脏脂蛋白受体对于理解正常的脂蛋白转运很重要。利用人肝细胞膜和成纤维细胞膜，直接比较了肝组织和非肝组织中LDL受体的特性。人肝细胞膜在5分钟内可逆地结合LDL。虽然成纤维细胞膜和肝细胞膜在37℃时都能饱和结合LDL，但成纤维细胞LDL受体的亲和力（Kd = 2.5×10⁻⁸ M）和数量（5.5×10¹²个位点/毫克膜蛋白）大于肝受体的亲和力（Kd = 10.8×10⁻⁸ M）和数量（0.5×10¹²个位点/毫克膜蛋白）。与在EDTA存在下无法结合LDL的成纤维细胞LDL受体不同，肝LDL受体对LDL的结合仅被EDTA部分阻断。LDL与其肝受体的结合高度依赖温度，利用放射性标记的LDL和胶体金标记的LDL进行的研究表明，在0 - 4℃时，LDL与肝细胞膜几乎没有结合（如果有结合也是极少的）。肝细胞膜受体（分子量约为270 000和330 000）与成纤维细胞LDL受体（分子量约为130 000）不同，并且这些蛋白质存在于缺乏成纤维细胞LDL受体的患者的肝细胞膜中。这些数据表明，表达的肝LDL受体具有与成纤维细胞LDL受体不同的独特特性，并且表达的蛋白质在基因上与成纤维细胞受体不同。
