Figure 1.

Scheme for alcohol metabolism in the liver. In the liver, alcohol is metabolized by the oxidative and non-oxidative pathway. In the oxidative pathway, the major pathway of alcohol digestion, alcohol is oxidized to acetaldehyde by various enzymes including alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP2E1), and catalase. Then, acetaldehyde is broken down into acetate, which is excreted out of the liver. Especially when excessive alcohol is consumed, CYP2E1 is activated and promotes formation of reactive oxygen species (ROS). The non-oxidative pathway accounts for a small amount of alcohol metabolism. Various enzymes nonoxidatively conjugates alcohol with different endogenous metabolites, producing fatty acid ethyl ester (FAEE), phosphatidylethanol (PEth), ethyl glucuronide (EtG), and ethyl sulfate (EtS). The byproducts generated during alcohol metabolism injure the liver by increasing lipid accumulation, inflammation, and fibrosis. Especially, acetaldehyde, the first metabolite of alcohol metabolism, is well known for toxic compounds. ROS, which are generated by activation of CYP2E1, are also considered as one of the major contributors of liver damage. In addition, acetate and non-oxidative metabolites are known to damage the liver.