CYP2E1-catalyzed alcohol metabolism: role of oxidant generation in interferon signaling, antigen presentation and autophagy.

Cytochrome P450 2E1 (CYP2E1) is one of two major enzymes that catalyze ethanol oxidation in the liver. CYP2E1 is also unique because it is inducible, as its hepatic content rises after continuous (chronic) ethanol administration, thereby accelerating the rate of ethanol metabolism and affording greater tolerance to heavy alcohol consumption. However, the broad substrate specificity of CYP2E1 and its capacity to generate free radicals from alcohol and other hepatotoxins, places CYP2E1 as a central focus of not only liver toxicity, but also as an enzyme that regulates cytokine signaling, antigen presentation, and macromolecular degradation, all of which are crucial to liver cell function and viability. Here, we describe our own and other published work relevant to the importance of CYP2E1-catalyzed ethanol oxidation and how this catalysis affects the aforementioned cellular processes to produce liver injury.