Saturable ethanol binding in rat liver mitochondria

The binding of ethanol to rat liver mitochondria is shown to be saturable a t physiologically relevant ethanol concentrations. This effect is reversibl e and is not observed in extracted mitochondrial phospholipids. Brief expos ure of the mitochondria to heat abolishes saturable ethanol binding. Previo usly, saturable ethanol binding was reported in rat liver microsomes. Taken together, the studies indicate that saturable ethanol binding motifs may b e widespread in cellular membranes. The possibility is;raised that incomple te expression of the hydrophobic effect in membrane assembly results in the expression of amphipathic packing defects which display an affinity for an d a sensitivity to ethanol. The presence of saturable binding modalities is reconciled with the long-standing consensus on the biodistribution of etha nol - that ethanol's interactions with tissue are negligible - on the groun ds that the affinities of ethanol and of water for membranes are similar; c onsequently, free ethanol concentrations are insensitive to the presence of tissue despite significant ethanol binding. A fraction of the binding site s possess submillimolar affinities for ethanol consistent with published fu nctional studies, both in vitro and in vivo, that reported submillimolar ef ficacies for ethanol. (C) 2000 Published by Elsevier Science B.V. All right s reserved.