Kakinohana O, Okuda Y
Department of Anesthesiology, School of Medicine, University of the Ryukyus, Okinawa.
Masui. 1993 Oct;42(10):1488-96.
The protein binding of lidocaine has been studied using gel filtration method. Thermodynamic calculation has been done on results of the experiment. We have found that the primary bond type of lidocaine with serum albumin is hydrophobic interaction, because entropy (delta S) is constantly positive (> 0) under these experimental conditions. The change of the binding ratio between lidocaine and serum albumin with changing pH results from the conformational change of the serum albumin, but the protein binding of lidocaine is also an exothermic reaction. The following conclusions have been obtained. (1) The binding of serum albumin with lidocaine is nonspecific and mainly the result of hydrophobic interaction. (2) At temperature 35 degrees C and pH 7.5, binding constant (K) and binding site (np) of bovine serum albumin with lidocaine are K = 5.9 x 10(3) M-1 and np = 103.5 x 10(-6) M, respectively. (3) Increasing binding ratio with increase in pH is the result of the increase in binding site. This involves the conformational change of albumin, especially that of N-B transition. (4) The binding of serum albumin with lidocaine is an exothermic reaction. Therefore, the binding of lidocaine with serum albumin increases as the temperature decreases.
已使用凝胶过滤法研究了利多卡因的蛋白结合情况。对实验结果进行了热力学计算。我们发现，利多卡因与血清白蛋白的主要结合键类型是疏水相互作用，因为在这些实验条件下熵（ΔS）始终为正（>0）。随着pH值变化，利多卡因与血清白蛋白结合率的改变是由于血清白蛋白的构象变化所致，但利多卡因的蛋白结合也是一个放热反应。得出了以下结论。（1）血清白蛋白与利多卡因的结合是非特异性的，主要是疏水相互作用的结果。（2）在35℃和pH 7.5条件下，牛血清白蛋白与利多卡因的结合常数（K）和结合位点数（np）分别为K = 5.9×10³ M⁻¹和np = 103.5×10⁻⁶ M。（3）随着pH值升高结合率增加是结合位点增加的结果。这涉及白蛋白的构象变化，尤其是N - B转变。（4）血清白蛋白与利多卡因的结合是放热反应。因此，随着温度降低，利多卡因与血清白蛋白的结合增加。
