In addition to ADH, a group of enzymes known as the cytochrome P450 isozymes, including CYP2E1, 1A2, and 3A4, also contribute to ethanol oxidation to acetaldehyde in the liver. These enzymes, which are present predominantly in a cell component called the endoplasmic reticulum (ER), become involved particularly after chronic ethanol intake. CYP2E1 is induced by chronic ethanol consumption and assumes an important role in metabolizing ethanol to acetaldehyde at elevated alcohol concentrations.3 Alcohol metabolism by CYP2E1 also produces highly reactive ROS, including hydroxyethyl, superoxide anions, and hydroxyl radicals. Finally, another enzyme called catalase, which is located in cell components called peroxisomes, also can oxidize ethanol (figure 4); however, quantitatively this is considered a minor pathway of ethanol oxidation. All of these oxidative pathways generate acetaldehyde, which then is rapidly metabolized further. This is done mainly by mitochondrial aldehyde dehydrogenase (ALDH2) to form acetate and NADH. Mitochondrial NADH is oxidized by the electron transport chain.
