INDUCTION OF LIPID-PROTEIN MISMATCH BY XENOBIOTICS WITH GENERAL MEMBRANE TARGETS

Many membrane-active xenobiotics, such as organic solvents or general anesthetics, are without specific target sites. A common, but as yet ill-defined physical mechanism of action is usually assumed. Displacement of 'boundary' lipid activators from functional membrane proteins by the induction of lipid/protein mismatch is now established as a candidate common physical mechanism. Multiple binding site kinetics demonstrate that xenobiotics can be strongly inhibitory at realistic membrane concentrations of below 4 mol%. A general equation for inhibition is derived.