游离脂肪酸对糖化人血清白蛋白苯二氮䓬结合位点结合动力学的影响。

Effect of free fatty acids on the binding kinetics at the benzodiazepine binding site of glycated human serum albumin.

作者信息

Keita Y, Kratzer W, Wörner W, Rietbrock N

机构信息

Department of Clinical Pharmacology, Johann Wolfgang Goethe University Clinic, Frankfurt/Main, Germany.

出版信息

Int J Clin Pharmacol Ther Toxicol. 1993 Jul;31(7):337-42.

PMID:7690351

Abstract

The effect of free fatty acids (FFA) and non-enzymatic glycation on the binding kinetics of dansylsarcosine (DS) to human serum albumin (HSA) was studied using the stopped-flow technique. The influence of FFA on the binding parameters of 25% glycated HSA depended on the type of fatty acid. The addition of stearic, oleic and linoleic acids in a concentration of 0.3 mmol/l showed no inhibitory effects on the association rate constant (k2) value for DS binding to 25% glycated HSA (k2 without FFA: 385 +/- 10 s-1, k2 with FFA > or = 385 +/- 10 s-1). In contrast, shorter chain fatty acids (hexanoic, octanoic, decanoic, lauric and myristic acids) showed marked inhibitory effects for 0.3 mmol/l FFA (k2 range: 233 +/- 32 to 69 +/- 5 s-1) and for 0.6 mmol/l FFA (k2 range: 125 +/- 3 to 20 +/- 4 s-1). The association rate constant (k2) as well as the affinity constant (KA) of DS were markedly affected by glycation: k2 was 686 +/- 61 s-1 for 7% glycated HSA, 385 +/- 10 s-1 for 25% glycated HSA and 209 +/- 12 s-1 for 50% glycated HSA. KA decreased from 6.1 +/- 2.9 x 10(5) M-1 for 7% glycated HSA, to 5.1 +/- 0.1 x 10(5) M-1 for 25% glycated HSA and to 1.3 +/- 0.6 x 10(5) M-1 for 50% glycated HSA.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

采用停流技术研究了游离脂肪酸（FFA）和非酶糖基化对丹磺酰肌氨酸（DS）与人血清白蛋白（HSA）结合动力学的影响。FFA对25%糖基化HSA结合参数的影响取决于脂肪酸的类型。添加浓度为0.3 mmol/l的硬脂酸、油酸和亚油酸对DS与25%糖基化HSA结合的缔合速率常数（k2）值无抑制作用（无FFA时k2：385±10 s-1，有FFA时k2≥385±10 s-1）。相比之下，短链脂肪酸（己酸、辛酸、癸酸、月桂酸和肉豆蔻酸）在0.3 mmol/l FFA时显示出显著抑制作用（k2范围：233±32至69±5 s-1），在0.6 mmol/l FFA时也有显著抑制作用（k2范围：125±3至20±4 s-1）。DS的缔合速率常数（k2）以及亲和常数（KA）受糖基化的显著影响：7%糖基化HSA的k2为686±61 s-1，25%糖基化HSA的k2为385±10 s-1，50%糖基化HSA的k2为209±12 s-1。KA从7%糖基化HSA的6.1±2.9×105 M-1降至25%糖基化HSA的5.1±0.1×105 M-1，再降至50%糖基化HSA的1.3±0.6×105 M-1。（摘要截断于250字）