Alcohols inhibit glucose transporters noncompetitively at a constant membrane concentration according to lipid theory

Various chemicals obey the Meyer-Overton correlation, in which potency increases exponentially with the partition coefficient. However, the principle remains unclear because of controversy between the lipid and protein theories. As the protein theory is based on the competitive inhibition of the non-membrane protein luciferase by alcohols and anesthetics, kinetic analysis was conducted on yeast hexose transporter Hxt2, a membrane protein. n -Alcohols (C ₂ -C ₈ ) inhibited Hxt2 noncompetitively and drug efflux according to the correlation. Thus, the alcohols interacting nonspecifically with membrane affect various membrane targets and inhibit Hxt2 from the lateral membrane-facing side, thereby supporting the lipid theory. The alcohols exerted similar potencies at a constant membrane concentration ( C _m ), regardless of the chain length. Consequently, the principle of the Meyer-Overton correlation is the maintenance of a constant C _m , whereas administered aqueous concentrations ( C _w ) only decrease with their partition coefficients. Intracellular C _m , but not extracellular C _w , provides an accurate measure of chemical potency.