Ethanol metabolism in zinc deficiency
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Description
Zinc plays a major role in ethanol metabolism and a deficiency of this metal is a consistent finding in chronic alcohol abusers. The mechanism by which zinc deficiency would impart its deleterious effects was the thesis of this research In vivo ethanol metabolic rate is significantly decreased in zinc deficient animals. An adaptive increase in ethanol metabolic rate is observed in rats on chronic alcohol consumption; however, decreased ethanol metabolic rate is observed in zinc deficient alcoholic rats. This decrease in ethanol clearance is due to a decrease in the activity of a zinc metalloenzyme, hepatic alcohol dehydrogenase. Alcohol dehydrogenase (ADH) reversibly catalyzes the oxidation of ethanol to acetaldehyde. The optimum activity of the low Km mitochondrial aldehyde dehydrogenase is dependent on mitochondrial membrane integrity. Loss of membranous structure results in decreased acetaldehyde metabolism. Mitochondrial enzyme studies do indicate that mitochondrial structure may be compromised in zinc deficient alcoholic rats resulting in decreased in vivo aldehyde dehydrogenase activity. Impaired acetaldehyde metabolism would result in increased intracellular levels of acetaldehyde which in turn would inhibit ADH. Since ADH reversibly catalyzes oxidation of alcohol to acetaldehyde, an increase in in vivo acetaldehyde concentrations would also have an inhibitory effect on the enzyme's activity and contribute towards decreased alcohol metabolism The deleterious effects of alcohol abuse are believed to be due to lipid peroxidation mediated by free radicals. Mitochondrial and microsomal lipid peroxidation was not increased in zinc deficiency or chronic ethanol consumption but was significantly increased if the two factors were combined, i.e. in zinc deficient alcoholic rats. Activity of enzymes associated with mitochondrial and microsomal membranes were also decreased in zinc deficient alcoholic animals. This suggests that the membrane integrity of these subcellular fractions is impaired. An imbalance in free radical metabolism has been postulated as the underlying mechanism of lipid peroxidation. Microsomal mixed function oxidases are increased and antioxidant enzyme activities are decreased suggesting that there may be an increase in the free radicals, resulting in increased lipid peroxidation. Secondly, acetaldehyde is being increasingly suggested as a hepatotoxin. Increased concentrations of acetaldehyde in vivo in alcohol consuming zinc deficient animals may also contribute to ethanol induced toxicity by reacting with functional groups of various enzymes and rendering them inactive. (Abstract shortened with permission of author.)