Metabolic and nutritional aspects of the effects of ethanol.

Unlike many pharmacologically active compounds that act by interfering more-or-less specifically with a single enzyme, receptor or transport system, the effects of ethanol may be less specific, involving interference with many different cellular processes. These. diffuse. effects have hindered attempts to understand the biochemical bases of ethanol-induced tolerance, dependence and tissue damage. The biochemical effects of ethanol include changes in receptor sensitivity (see, e.g., Kuriyama et al., 1981; Tabakoff et al., 1980), energy metabolism (Kalant et al., 1978), cellular Ca2+ concentrations (Ross, 1976), neurotransmitter concentrations and metabolism (for a review see Bardsley & Tipton, 1980), cell permeability (Lieber & De Carli, 1977), the activities of a number of enzymes, particularly those associated with the endoplasmic reticulum (see, e.g., Ishii et al., 1973) and protein turnover (see, e.g. Mrarland & Bessensen, 1977; Tewari & Noble, 1979). It may be that many of these diverse effects result from the changes in cellular redox state that accompany ethanol metabolism (see Cederbaum et al., 1977; Lieber, 1973) and the direct effects of ethanol on cell membranes (see, e.g., Littleton, 1980; Goldstein et al., 1982), but such simple aetiologies have not been firmly established, and other primary effects, including direct or indirect effects of the metabolite acetaldehyde (see Truitt & Walsh, 1971; Davis et al., 1980; Melchior, 1981), could be important. The actions of ethanol can be further complicated by secondary effects. An increased sensitivity to some toxic compounds, and a related insensitivity to the effects of certain drugs, can result from the ethanol-induced proliferation of the endoplasmic reticulum (see Strubelt, 1980). Nutritional insufficiencies are frequently associated with chronic ethanol consumption, and the effects of these will also complicate the symptoms seen in many alcoholics.