Meijer D K, Scholtens H B, Hardonk M J
Pharm Weekbl Sci. 1982 Jun 25;4(3):57-70. doi: 10.1007/BF01962246.
Glycoproteins represent a wide variety of macromolecules with important physiological functions. Characteristic variations in carbohydrate composition and plasma concentration of these proteins may occur during pathological conditions. Steady-state plasma concentrations are determined by release from normal or diseased tissues and simultaneous clearance from the general circulation. The liver occupies a central position in the production but also clearance and catabolism of such glycoproteins. A number of specialized receptor-mediated transport processes for different types of glycoproteins in this organ is reviewed. Membrane recognition is generally followed by absorptive endocytosis and vesicle transport to lysosomes, Golgi system and/or bile canaliculis. The charge of the protein, the nature of the terminal sugar residue or complex formation with other glycoproteins may determine the extent of uptake in the various cell types of the liver. By means of these transport processes the liver is able to remove potentially dangerous macromolecules such as denatured proteins, aggressive enzymes and immunocomplexes from the general circulation. Drugs can bind to some of these proteins or may interact with the hepatic transport or catabolism processes. Special attention is paid to the hepatic clearance of asialoglycoproteins with terminal galactose groups. Intestinal alkaline phosphatase is used as a model compound to characterize the pharmacokinetic profiles of hepatic uptake and biliary excretion in the rat in vivo and isolated perfused rat livers. Histochemical and electron-microscopic studies demonstrated a galactose-specific, receptor-mediated endocytotic process, mainly but not exclusively localized in centrolobular hepatocytes. Drug interactions with these processes will be the subject of further investigations.
糖蛋白代表了具有重要生理功能的多种大分子。在病理状态下,这些蛋白质的碳水化合物组成和血浆浓度可能会出现特征性变化。稳态血浆浓度由正常或患病组织的释放以及同时从全身循环中的清除来决定。肝脏在这类糖蛋白的产生、清除和分解代谢中占据核心地位。本文综述了该器官中针对不同类型糖蛋白的一些特殊的受体介导转运过程。膜识别通常之后是吸收性内吞作用以及囊泡运输至溶酶体、高尔基体系统和/或胆小管。蛋白质的电荷、末端糖残基的性质或与其他糖蛋白的复合物形成可能决定肝脏各种细胞类型中的摄取程度。通过这些转运过程,肝脏能够从全身循环中清除潜在危险的大分子,如变性蛋白、活性酶和免疫复合物。药物可以与其中一些蛋白质结合,或者可能与肝脏转运或分解代谢过程相互作用。特别关注了具有末端半乳糖基团的去唾液酸糖蛋白的肝脏清除。肠碱性磷酸酶被用作模型化合物,以表征大鼠体内和离体灌注大鼠肝脏中肝脏摄取和胆汁排泄的药代动力学特征。组织化学和电子显微镜研究表明存在一种半乳糖特异性的、受体介导的内吞过程,主要但并非仅局限于小叶中央肝细胞。药物与这些过程的相互作用将是进一步研究的主题。