Biological water and its role in the effects of alcohol.
Alcohol and water compete with each other on target membrane molecules, specifically, lipids and proteins near the membrane surface. The basis for this competition is the hydrogen bonding capability of both compounds. But alcohol's amphiphilic properties give it the capability to be attracted simultaneously to both hydrophobic and hydrophilic targets. Thus, alcohol could bind certain targets preferentially and displace water, leading to conformational consequences. This article reviews the clustering and organized character of biological water, which modulates the conformation of membrane surface molecules, particularly receptor protein. Any alcohol-induced displacement of biological water on or inside of membrane proteins creates the opportunity for allosteric change in membrane receptors. This interaction may also prevail in organelles, such as the Golgi apparatus, which have relatively low concentrations of bulk water. Target molecules of particular interest in neuronal membrane are zwitteronic phospholipids, gangliosides, and membrane proteins, including glycoproteins. FTIR and NMR spectroscopic evidence from model membrane systems shows that alcohol has a nonstereospecific binding capability for membrane surface molecules and that such binding occurs at sites that are otherwise occupied by hydrogen-bonded water. The significance of these effects seems to lie in the need to learn more about biological water as an active participant in biochemical actions. Proposed herein is a new working hypothesis that the molecular targets of ethanol action most deserving of study are those where water is trapped and there is little bulk water. Proteins (enzymes and receptors) certainly differ in this regard, as do organelles.
Klemm
W R
WR
Department Veterinary Anatomy & Public Health, Texas A&M University, College Station 77843, USA.
D000818:Animals; D001667:Binding, Competitive; D001834:Body Water / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004361:Drug Tolerance; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding
D000431:Ethanol