The Metabolism of Alcohol and Its Implications for the Pathogenesis of Disease
The demonstration that alcohol exerts some intrinsic hepatotoxicity independent of nutritional deficiencies led to a broad-based search for the mechanism involved. The hepatocyte contains three main pathways for ethanol metabolism, each located in a different subcellular compartment: the alcohol dehydrogenase (ADH) pathway of the cytosol or the soluble fraction of the cell, the microsomal ethanol oxidizing system (MEOS) located in the endoplasmic reticulum, and catalase located in the peroxisomes. Human ADH is a dimeric zinc metalloenzyme for which five classes have been distinguished. Subunits hybridize within classes but not between classes. The possible pathogenic role of a nonoxidative pathway of alcohol metabolism to form fatty acid ethyl esters was suggested by Laposata and Lange. In the presence of severe alcoholic liver disease this acceleration disappears, and on occasion there may be an actual reduction in blood alcohol clearance. Acetaldehyde is produced from ethanol in both the ADH and MEOS pathways.