ETHANOL EFFECTS ON MEMBRANE-BOUND ENZYMES

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It has been hypothesized that the actions of ethanol result from its ability to perturb the structure of neuronal membrane lipids. Changes in the activities of membrane-bound enzymes, which are modulated by the properties of surrounding lipids, may indicate specific sites of action of ethanol within the neuronal membrane, and may persist beyond the time that ethanol is present in tissues, therefore serving as objective measures of alcohol consumption. It has also been suggested that certain enzymes, in particular monoamine oxidase (MAO), may be markers of a genetic predisposition to alcoholism. We previously found that ethanol in vitro inhibits the B-form of MAO in brain and platelet tissue, and that receptor- coupled adenylate cyclase (AC) activity in brain is altered by chronic ethanol ingestion. These enzyme activities were evaluated in platelets of alcoholics and controls. There was no significant difference in MAO activity per se between the two groups, but inhibition of MAO activity by ethanol in vitro was significantly greater, while stimulation of AC activity by fluoride and other agents was significantly lower, in platelets of alcoholics than controls. This latter finding has been replicated in three independent groups of alcoholics and controls. The differences in enzyme properties were long-lasting, and could be used in discriminant analysis to correctly classify 73% of controls and 75% of alcoholics. More work is needed to determine whether the differences are a consequence of alcohol consumption or may reflect a predisposition to alcoholism. Studies of the effects of ethanol in vivo on enzymes of neurotransmitter metabolism made use of an irreversible inhibitor of DOPA decarboxylase, monofluoromethyl DOPA. During ethanol withdrawal, dopamine turnover was reduced in most brain areas. while norepinephrine turnover was increased. particularly in brainstem. These studies further elucidate ethanol effects on neuronal activity, and suggest pharmacological therapies that may be developed to counteract specific symptoms of ethanol withdrawal.