Halothane, an inhalational anesthetic agent, increases folding stability of serum albumin

Inhalational anesthetic agents are known to alter protein function, but the nature of the interactions underlying these effects remains poorly underst ood. We have used differential scanning calorimetry to study the effects of the anesthetic agent halothane on the thermally induced unfolding transiti on of bovine serum albumin. We find that halothane (0.6-10 mM) stabilizes t he folded state of this protein, increasing its transition midpoint tempera ture : from 62 to 71 degrees C. Binding of halothane to the native state of serum albumin thus outweighs any non-specific interactions between the the rmally unfolded state of serum albumin and halothane in this concentration range. Based on the average enthalpy change Delta II for unfolding of 170 k cal/mol. the increase from 62 to 71 degrees C corresponds to an additional Gibbs energy of stabilization (MC) due to halothane of more than 4 kcal/mol . Analysis of the dependence of Delta Delta G on halothane concentration sh ows that thermal unfolding of a bovine serum albumin molecule is linked to the dissociation of about one halothane molecule at lower halothane concent rations and about six at higher halothane concentrations. Serum albumin is the first protein that has been shown tu be stabilized by an inhalational a nesthetic. (C) 1999 Elsevier Science B.V. All rights reserved.