ETHANOL-METABOLISM IN THE BRAIN

Acetaldehyde is suspected of being involved in the central mechanism o f central nervous system depression and addiction to ethanol, but in c ontrast to ethanol, it can not penetrate easily from blood into the br ain because of metabolic barriers. Therefore, the possibility of ethan ol metabolism and acetaldehyde formation inside the brain has been one of the crucial questions in biomedical research of alcoholism. This a rticle reviews the recent progress in this area and summarizes the evi dence on the first stage of ethanol oxidation in the brain and the spe cific enzyme systems involved. The brain alcohol dehydrogenase and mic rosomal ethanol oxidizing systems, including cytochrome P450 II E1 and catalase are considered. Their physicochemical properties, the isofor m composition, substrate specificity, the regional and subcellular dis tribution in CNS structures, their contribution to brain ethanol metab olism, induction under ethanol administration and the role in the neur ochemical mechanisms of psychopharmacological and neurotoxic effects o f ethanol are discussed. In addition, the nonoxidative pathway of etha nol metabolism with the formation of fatty acid ethyl esters and phosp hatidylethanol in the brain is described.