[Ethanol metabolism and pathobiochemistry of organ damage--1992. II. Relation between ethanol metabolism and free radicals, and the metabolism of saccharides and amino acids. Ethanol as a carcinogen. Drug interactions with ethanol].

Ethanol metabolism induces formation of free radicals which are responsible for lipid peroxidation of biological membranes with subsequent aldehyde formation (malondialdehyde,4-hydroxy-nonenal). These aldehydes are competitive or mixed inhibitors of aldehyde dehydrogenase, and they cause an increase in hepatocellular toxicity of aldehydes. The activity of antioxidative systems in human body after chronic as well as acute ethanol intake is being reduced. Interference of ethanol metabolism and gluconeogenesis is caused by inhibition of intake substrates or by decrease NADH/NAD+, ratio in hepatocyte. The blood level of glucose decreases, lactate level increases as well as the ration of lactate, pyruvate and NADH/NAD+ which inhibit cytosole pyruvate carboxykinase. An acute ethanol administration reduces the concentration of most amino acids in plasma by ethanol oxidation impacts on increase of NADH/NAD+ ratio or by mechanism mediated by beta-adrenergic receptors. Chronic alcoholics develop tolerance to decreased plasmatic levels of amino acids. Accumulation of proteins in liver may be explained by larger amount of proteins binding to fatty acids, and also by diminished degradation of proteins with decreasing autophagosome and autolysosome formations. Alcohol is one of carcinogenic factors. Ethanol, acetaldehyde and originating free radicals impaired the DNA repairing enzyme. Binding itself to DNA, acetaldehyde changes DNA properties. Ethanol may also function as a co-carcinogen due to its ability to increase disolution and absorption of carcinogens. Chronic alcoholism induces cytochrome P450 which takes part in the activation and metabolism of carcinogens. Mutual interaction of drugs metabolism and ethanol is connected mainly with cytochrome P450-MEOS. Acute ethanol intake inhibits MEOS, as MEOS gives preference to ethanol as a substrate, however, chronic alcoholism induces MEOS.(ABSTRACT TRUNCATED AT 250 WORDS)