Lefort G P, Stolk J M, Nisula B C
Endocrinology. 1984 Oct;115(4):1551-7. doi: 10.1210/endo-115-4-1551.
It is widely known that removal of sialic acid from the carbohydrate chains of glycoproteins in vitro drastically reduces their survival time in the circulation; however, it is not known whether desialylation plays a significant role in the metabolism of sialylated serum glycoproteins in vivo. We have studied the metabolism of hCG and desialylated hCG (as-hCG) in rat serum and liver in vivo to assess this putative metabolic pathway for glycoprotein hormones. A single injection of as-hCG into rats was followed by its rapid removal from the circulation, principally by the liver, and its degradation into fragments of the hCG beta-subunit that lacked the carboxy-terminal peptide antigenic determinant. Continuous infusion of desialylated fetuin (as-fetuin) at a high rate along with as-hCG dramatically reduced accumulation of the beta-subunit fragments in liver and resulted in increased serum levels of as-hCG. Consequently, the MCR of as-hCG was reduced from 301 +/- 10.3 ml/h (mean +/- SE) to 13.4 +/- 1.15 ml/h by infusion of as-fetuin, which is known to compete for hepatic receptors for galactose-terminated glycoproteins. In contrast, coinfusion of as-fetuin with hCG did not influence the MCR of hCG. Furthermore, there was no serum accumulation of hCG desialylated in its hCG beta carboxy-terminal portion, with or without as-fetuin, and the quantity and pattern of immunoreactive hCG products in liver homogenate were not affected by coinfusion of as-fetuin with hCG. Thus, blockade of hepatic receptors for galactose-terminated glycoproteins did not impede hCG turnover in the circulation, impair hepatic catabolism of hCG, or lead to the accumulation of desialylated products of hCG in plasma. These data indicate that in the rat, there is negligible catabolism of glycoproteins, such as hCG, by a pathway that involves peripheral desialylation and subsequent hepatic uptake via receptors for galactose-terminated glycoproteins.
众所周知，在体外从糖蛋白的碳水化合物链中去除唾液酸会大大缩短其在循环中的存活时间；然而，尚不清楚去唾液酸化在体内唾液酸化血清糖蛋白的代谢中是否起重要作用。我们在体内研究了大鼠血清和肝脏中hCG和去唾液酸化hCG（as-hCG）的代谢，以评估这种推测的糖蛋白激素代谢途径。向大鼠单次注射as-hCG后，它会迅速从循环中清除，主要是通过肝脏，并降解为缺乏羧基末端肽抗原决定簇的hCGβ亚基片段。以高速度持续输注去唾液酸化胎球蛋白（as-胎球蛋白）以及as-hCG，可显著减少肝脏中β亚基片段的积累，并导致as-hCG血清水平升高。因此，通过输注as-胎球蛋白，as-hCG的代谢清除率（MCR）从301±10.3 ml/h（平均值±标准误）降至13.4±1.15 ml/h，已知as-胎球蛋白会竞争肝脏中对半乳糖末端糖蛋白的受体。相比之下，as-胎球蛋白与hCG共同输注并不影响hCG的MCR。此外，无论有无as-胎球蛋白，在其hCGβ羧基末端部分去唾液酸化的hCG都不会在血清中积累，并且肝脏匀浆中免疫反应性hCG产物的数量和模式不受as-胎球蛋白与hCG共同输注的影响。因此，对半乳糖末端糖蛋白肝脏受体的阻断不会妨碍循环中hCG的周转，不会损害hCG的肝脏分解代谢也不会导致血浆中hCG去唾液酸化产物的积累。这些数据表明，在大鼠中，通过涉及外周去唾液酸化以及随后通过对半乳糖末端糖蛋白的受体进行肝脏摄取的途径，糖蛋白（如hCG）的分解代谢可以忽略不计。
