CYP2E1 is part of the Microsomal Ethanol Oxidizing System (MEOS) accounting for up to 10% of ethanol oxidation in the liver (Tanaka et al., 2000). Once the ADH pathway becomes saturated due to high ethanol concentrations, the MEOS pathway activity increases (Lieber, 1997). By the MEOS pathway, CYP2E1 metabolizes ethanol and other substrates into toxic metabolites creating free radicals in the form of reactive oxygen (O2) intermediates creating oxidative stress leading to liver damage. CYP2E1 uses O2 to oxidize ethanol to aldehyde and NADPH to NADP+. While generally used biosynthetically, NADPH can be regenerated from NADP+ with the conversion of NADH to NAD+. In the absence of NADPH, oxidation of ethanol to aldehyde by CYP2E1 results in superoxides (Zakhari, 2006). An excess of reduced NADH in addition to the increased activity of hydrogen shuttles in mitochondria, results in an increased intake of electrons leading to an increase of superoxide anions (Seitz and Stickel, 2007). The increased creation of Reactive Oxygen Species, or ROS, as a result from the shift in cellular redox state, coupled with the reduced ability to clear
