Titration calorimetry of anesthetic-protein interaction: negative enthalpy of binding and anesthetic potency.

AUTOR(ES)

Ueda, I

RESUMO

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.

Documentos Relacionados

• Manipulation of rat brain fatty acid composition alters volatile anesthetic potency.
• The enthalpy of the alanine peptide helix measured by isothermal titration calorimetry using metal-binding to induce helix formation
• Local anesthetic-membrane interaction: a multiequilibrium model.
• Evaluation of linked protonation effects in protein binding reactions using isothermal titration calorimetry.
• Beta-Endorphin: dissociation of receptor binding activity from analgesic potency.