Saturable ethanol binding in rat liver mitochondria.
The binding of ethanol to rat liver mitochondria is shown to be saturable at physiologically relevant ethanol concentrations. This effect is reversible and is not observed in extracted mitochondrial phospholipids. Brief exposure of the mitochondria to heat abolishes saturable ethanol binding. Previously, saturable ethanol binding was reported in rat liver microsomes. Taken together, the studies indicate that saturable ethanol binding motifs may be widespread in cellular membranes. The possibility is raised that incomplete expression of the hydrophobic effect in membrane assembly results in the expression of amphipathic packing defects which display an affinity for and a sensitivity to ethanol. The presence of saturable binding modalities is reconciled with the long-standing consensus on the biodistribution of ethanol - that ethanol's interactions with tissue are negligible - on the grounds that the affinities of ethanol and of water for membranes are similar; consequently, free ethanol concentrations are insensitive to the presence of tissue despite significant ethanol binding. A fraction of the binding sites possess submillimolar affinities for ethanol consistent with published functional studies, both in vitro and in vivo, that reported submillimolar efficacies for ethanol.
Channareddy
S
S
Department of Pathology, Anatomy, and Cell Biology, Medical College of Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
Nguyen
N T
NT
Janes
N
N
D000818:Animals; D001665:Binding Sites; D002250:Carbon Radioisotopes; D000431:Ethanol / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D007700:Kinetics; D008563:Membrane Lipids / Q000302:isolation & purification / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D010743:Phospholipids / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000378:metabolism; D014867:Water / Q000378:metabolism
D002250:Carbon Radioisotopes; D008563:Membrane Lipids; D010743:Phospholipids; D014867:Water; D000431:Ethanol; D013395:Sucrose