Ueda I, Yamanaka M
Department of Anesthesia, Department of Veterans Administration Medical Center, Salt Lake City, Utah 84148, USA.
Biophys J. 1997 Apr;72(4):1812-7. doi: 10.1016/S0006-3495(97)78827-1.
Anesthetic potency increases at lower temperatures. In contrast, the transfer enthalpy of volatile anesthetics from water to macromolecules is usually positive. The transfer decreases at lower temperature. It was proposed that a few selective proteins bind volatile anesthetics with negative delta H, and these proteins are involved in signal transduction. There has been no report on direct estimation of binding delta H of anesthetics to proteins. This study used isothermal titration calorimetry to analyze chloroform binding to bovine serum albumin. The calorimetrically measured delta H cal was -10.37 kJ.mol-1. Thus the negative delta H of anesthetic binding is not limited to signal transduction proteins. The binding was saturable following Fermi-Dirac statistics and is characterized by the Langmuir adsorption isotherms, which is interfacial. The high-affinity association constant, K, was 2150 +/- 132 M-1 (KD = 0.47 mM) with the maximum binding number, Bmax = 3.7 +/- 0.2. The low-affinity K was 189 +/- 3.8 M-1 (KD = 5.29 mM), with a Bmax of 13.2 +/- 0.3. Anesthetic potency is a function of the activity of anesthetic molecules, not the concentration. Because the sign of delta H determines the temperature dependence of distribution of anesthetic molecules, it is irrelevant to the temperature dependence of anesthetic potency.
在较低温度下麻醉效能会增强。相比之下，挥发性麻醉剂从水转移至大分子的焓变通常为正值。在较低温度下这种转移会减少。有人提出一些选择性蛋白质以负的ΔH结合挥发性麻醉剂，并且这些蛋白质参与信号转导。尚未有关于直接估算麻醉剂与蛋白质结合的ΔH的报道。本研究采用等温滴定量热法分析氯仿与牛血清白蛋白的结合。量热法测得的ΔHcal为-10.37 kJ·mol-1。因此，麻醉剂结合的负ΔH并不局限于信号转导蛋白。该结合遵循费米-狄拉克统计是可饱和的，其特征为朗缪尔吸附等温线，是界面性的。高亲和力缔合常数K为2150±132 M-1（KD = 0.47 mM），最大结合数Bmax = 3.7±0.2。低亲和力K为189±3.8 M-1（KD = 5.29 mM），Bmax为13.2±0.3。麻醉效能是麻醉剂分子活性的函数，而非浓度的函数。由于ΔH的符号决定了麻醉剂分子分布的温度依赖性，所以它与麻醉效能的温度依赖性无关。
