Dehydration: A new alcohol theory

doi:10.1016/0741-8329(90)90060-P

Alcohol

Volume 7, Issue 1, January–February 1990, Pages 49-59

https://doi.org/10.1016/0741-8329(90)90060-P Get rights and content

Abstract

A central belief about ethanol is that it acts mainly by partitioning into the lipid bilayer of membranes. Newer ideas focus on the neuronal synapse and suggest that ethanol can allosterically change protein conformation, as is suggested by studies on GABA-receptor-mediated chloride uptake and on (Na⁺-K⁺)-ATPase. Several studies from my laboratory suggest that ethanol enhances enzymatic cleavage of sialic acid (SA) from gangliosides, and perhaps also glycoproteins, but does so without stimulating enzyme activity, suggesting conformational changes that affect accessibility. I propose a new model for the cell membrane in the synaptic region, which features gangliosides surrounding membrane proteins, with an interspersed film of water creating hydrogen bonds that anchor SA moieties to membrane protein. I believe that we should consider the possibility that an important action of ethanol, and polar anesthetics, is due to hydrophilic, not hydrophobic, properties and the ability to dehydrate the cell-surface microdomain. Our laboratory has recently advanced the theory that ethanol dehydrates a “solvent regulatory site” of membrane (Na⁺-K⁺)-ATPase. This principle might be extended to other enzymes and receptor proteins, as well as to the accessibility of sialoglycoconjugates to sialidase (neuraminidase). Hydrogen bonding between SA and polar regions of receptor protein, and the conformation on both imposed by it, would surely be changed by minor degrees of dehydration and substitution of alcohol molecules for water. Ethanol, unlike water, can only hydrogen bond “at one end”. Displacement of water by ethanol would not only “free” the SA groups and make them more vulnerable to enzymatic cleavage but also could simultaneously change the conformation of receptor protein. Similarly, ethanol may displace water that links the polar heads of phospholipids to polar portions of receptor proteins. Ethanol may have an even more important and direct effect of substituting for hydrogen-bonded water within protein itself.

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Dehydration: A new alcohol theory

Abstract

Biochim. Biophys. Acta.

Biochim. Biophys. Acta

Arch. Biochem. Biophys.

Alcohol

Trends Physiol. Sci.

J. Electrostatics

Neuroscience

Biochim. Biophys. Acta.

Life Sci.

Alcohol

Biochem. Biophys. Res. Commun.

Methods Enzymol.

Lancet

Pharmacol. Biochem. Behav.

Alcohol

Biochim. Biophys. Acta.

Neurochem. Int.

Biochem. Pharmacol.

Drug Alcohol Depend.

Biochim. Biophys. Acta

Biochem. Biophys. Res. Commun.

Brain Res.

Brain Res.

Biochim. Biophys. Acta

J. Magn. Reson.

Effect of short-chain primary alcohols on fluidity and activity of sarcoplasmic reticulum membranes

Biochemistry

Behavioral manifestations of ethanol intoxication and physical dependence

Nuclear magnetic resonance observations in alcoholic cerebral disorder and the role of vasopressin

Lancet

Synaptosomal sialyltransferase glycosylates surface proteins that are inaccessible to the action of membranebound sialidase

J. Neurochem.

Gangliosides as receptor modulators

Mechanism of anesthesia: the potency of four derivatives of octane corresponds to their hydrogen bonding capacity

Lipids

Effect of single and repeated injections of ethanol on lipid and protein-bound sialic acid in mice of different ages

Alcohol.: Clin. Exp. Res.

Ethanol-induced hydrolysis of brain sialoglycoconjugates in the rat: effect of sialic acid in antagonizing ethanol intoxication

Alcohol.: Clin. Exp. Res.

Integral membrane glycoproteins in cell-cell and cell-substratum adhesion

Factors affecting the distribution and measurement of ethanol in the body

Water structure-dependent charge transport in protein

Biomembranes. Molecular structure and function

Pharmacology of alcohol

Alcohol and biological membranes

The binding of alcohol to brain membranes

Ganglioside receptors: a brief overview and introductory remarks

Does a “moderate” alcohol intake damage the brain?

J. Neurol. Neurosurg. Psychiatry

Ethanol-induced changes in neuronal membrane order. An NMR study

Biochim. Biophys. Acta

Neurochemical actions of anesthetic drugs on the gamma-aminobutyric acid receptor-chloride channel complex

J. Pharmacol. Exp. Ther.

Alcohol and biological membranes

On the relationship between alcohol narcosis and membrane fluidity

Subst. Alcohol Actions Misuse

Role of glycoproteins during early mammalian embryogenesis