Alcoholic Liver Disease

ETHANOL METABOLISM AND PATHOPHYSIOLOGY More than one enzyme system is capable of metabolizing alcohol in the liver. Enzymes that have received the greatest attention include alcohol dehydrogenase, aldehyde dehydrogenase, and the microsomal ethanol-oxidizing system (MEOS) (Fig. 1). The relative importance of each of these pathways is being investigated. When physiologic circumstances are normal and blood levels of alcohol are low, the enzyme of major importance is alcohol dehydrogenase. This enzyme catalyzes the conversion of alcohol to acetaldehyde, and aldehyde dehydrogenase subsequently catalyzes the conversion of acetaldehyde to acetate. Alcohol dehydrogenase catalysis changes the oxidationreduction state in the cell by increasing the ratio of reduced nicotinamide adenine dinucleotide (NADH) to the oxidized form (NAD), which has important implications for other cellular processes, including the generation of free radicals, inhibition of other enzyme systems, and accumulation of fat. Also, an isoform of alcohol dehydrogenase occurs within the gastric mucosa, although the clinical importance of the gastric component of alcohol metabolism is debated.