Drug-protein binding kinetics in patients with Type I diabetes
Drug-protein binding kinetics in patients with Type I diabetes
复制标题
I 型糖尿病患者的药物-蛋白质结合动力学
DOI：
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发表时间：
2005
影响因子：
2.9
通讯作者：
N. Rietbrock
中科院分区：
文献类型：
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作者：
W. Wörner;A. Preißner;N. Rietbrock
本文对17例Ⅰ型糖尿病患者和19例健康志愿者的血清进行了检测，以评价药物与血清白蛋白位点Ⅱ结合的动力学是否在糖尿病中发生改变。停流测量显示，糖尿病患者的荧光标记物丹酰肌氨酸的结合速度和亲和常数（160 s−1和2.0 × 105 l·mol−1）显著低于非糖尿病患者（196 s −1和4.0 × 105 l·mol−1）。解离速度没有差异[20.3 s-1 vs. 19.4 s-1]。尽管排除了白蛋白浓度降低的患者，但糖尿病患者的白蛋白浓度显著低于健康志愿者。白蛋白糖基化降低与结合速度增加之间存在显著相关性。解离速率常数与游离脂肪酸/人血清白蛋白的摩尔浓度比相关。因此，糖基化的程度和每摩尔白蛋白结合的脂肪酸的量都可以影响药物与位点II结合的动力学。在I型糖尿病患者中较低的亲和力是由于糖蛋白浓度的增加。
SummarySera from 17 patients with Type I diabetes and 19 healthy volunteers have been examined to evaluate whether the kinetics of the binding of drugs to Site II of serum albumin is altered in diabetes. Stopped-flow measurements showed that the association velocity and the affinity constants of the fluorescent marker dansylsarcosine were significantly lower in diabetics (160 s−1 and 2.0 × 105 l·mol−1) than in non-diabetics (196s−1 and 4.0 × 105 l·mol−1). The dissociation velocity was not different [20.3 s−1 vs. 19.4 s−1]. Although patients with a reduced albumin concentration were excluded the diabetics had significantly lower concentrations than the healthy volunteers. There was a significant correlation between decreased glycosylation of albumin and increased association velocity. The dissociation velocity constants were correlated with the molar concentration ratio of free fatty acids/human serum albumin. Thus, the extent of glycosylation and the amount of fatty acids bound per mole albumin can both affect the kinetics of drug binding to Site II. The lower affinity in patients with Type I diabetes is due to the increased in the glycoalbumin concentration.