Tsuchiya S, Sakurai T, Sekiguchi S
Biochem Pharmacol. 1984 Oct 1;33(19):2967-71. doi: 10.1016/0006-2952(84)90595-1.
To estimate the functional change occurring in human serum albumin by nonenzymatic glucosylation, glucosylated human serum albumin was prepared by in vitro incubation with glucose. The rate of glucosylation proceeded as a first-order reaction. The binding of sulfonylureas to serum albumin was determined by equilibrium gel filtration. Through this method, it was possible to estimate the binding capacity of a low water solubility drug with a high affinity to protein. The amounts of the sulfonylureas bound to glucosylated HSA decreased by 44% with tolazamide and acetohexamide, 50% with glibenclamide, and 52% with tolbutamide, compared to human serum albumin (HSA). This suggests that a high concentration of glucosylated HSA in diabetic patients may possibly cause an increase in free drug concentration exceeding normal levels. This study shows that the decrease in the binding capacity of sulfonylureas with protein is due to the modification of albumin molecules by the covalent binding of glucose.
为了评估非酶糖基化作用下人血清白蛋白发生的功能变化，通过与葡萄糖进行体外孵育制备了糖基化人血清白蛋白。糖基化速率呈一级反应进行。通过平衡凝胶过滤法测定磺脲类药物与血清白蛋白的结合情况。通过这种方法，可以估算出对蛋白质具有高亲和力的低水溶性药物的结合能力。与正常人血清白蛋白（HSA）相比，糖基化HSA结合的甲苯磺丁脲和醋磺己脲减少了44%，格列本脲减少了50%，甲苯磺丁脲减少了52%。这表明糖尿病患者体内高浓度的糖基化HSA可能会导致游离药物浓度超过正常水平而增加。本研究表明，磺脲类药物与蛋白质结合能力的下降是由于葡萄糖的共价结合对白蛋白分子进行了修饰。
