Ethanol Metabolism in the Liver, the Induction of Oxidant Stress, and the Antioxidant Defense System

The liver metabolizes ethanol through three enzymatic pathways: alcohol dehydrogenase (ADH), cytochrome p450 (also called MEOS), and catalase. Alcohol dehydrogenase class I (ADH1) is considered the most important enzyme for the metabolism of ethanol, MEOS and catalase (CAT) are considered minor alternative pathways. However, contradicting experiments suggest that the non-ADH1 pathway may have a greater relevance for the metabolism of ethanol than previously thought. In some conditions, ethanol is predominately metabolized to acetaldehyde via cytochrome P450 family 2 (CYP2E1), which is involved in the generation of reactive oxygen species (ROS), mainly through electron leakage to oxygen to form the superoxide (O-2(center dot-)) radical or in catalyzed lipid peroxidation. The CAT activity can also participate in the ethanol metabolism that produces ROS via ethanol directly reacting with the CAT-H2O2 complex, producing acetaldehyde and water and depending on the H2O2 availability, which is the rate-limiting component in ethanol peroxidation. We have shown that CAT actively participates in lactate-stimulated liver ethanol oxidation, where the addition of lactate generates H2O2, which is used by CAT to oxidize ethanol to acetaldehyde. Therefore, besides its known role as a catalytic antioxidant component, the primary role of CAT could be to function in the metabolism of xenobiotics in the liver.

Automated summary

The liver metabolizes ethanol through three enzymatic pathways, with alcohol dehydrogenase considered the most important enzyme. Contradicting experiments suggest that non-alcohol dehydrogenase pathways may be more relevant for ethanol metabolism than previously thought. Ethanol can be metabolized to acetaldehyde mainly through cytochrome P450, which generates reactive oxygen species. Catalase can also participate in ethanol metabolism by reacting with ethanol to produce acetaldehyde. Besides its role as an antioxidant, catalase may have a primary role in xenobiotic metabolism in the liver.