The lipid/protein interface as xenobiotic target site - Kinetic analysis of the nicotinic acetylcholine receptor

Membrane proteins are known to be solvated and functionally activated by a fixed number of lipid molecules whose multiple binding can be described by Adair-type binding equations. Lipophilic xenobiotics such as general anesth etics may act by competitive displacement of protein-bound lipids. A kineti c equation is now presented for various binding stoichiometries of lipid an d xenobiotic, and microscopic binding constants of anesthetics and organic solvents are derived from two independent assay systems for the enhancement of agonist binding to the nicotinic acetylcholine receptor. These constant s lead to the first available free! energy estimate (-6.4 kcal/mol) for the binding of membrane lipid to an integral membrane protein.