The average rate at which alcohol is eliminated from the body is ∼7 g/h, which translates to ∼1 drink/h. Alcohol undergoes first pass gastric metabolism by the enzyme alcohol dehydrogenase (ADH). However, most alcohol oxidation occurs in the liver. Alcohol is metabolized to acetaldehyde primarily by alcohol dehydrogenase (ALD) and the cytochrome P450 2E1 (CYP2E1). This later pathway is particularly relevant following chronic alcohol abuse. Acetaldehyde is converted to acetate in the mitochondria by the enzyme acetaldehyde dehydrogenase (ALDH) type 2. Most of the acetate produced enters the systemic circulation and is activated to acetyl coenzyme A (CoA), a key intermediate metabolite in peripheral tissues. Acetaldehyde can form adducts that can produce injury through activation of immune responses. During the oxidative process, both ADH and ALDH reactions reduce NAD+ to NADH, shifting the cellular redox ratio, thereby affecting several NAD+ requiring enzymes like lactate and pyruvate dehydrogenase and affecting pathways including glycolysis, citric acid cycle, fatty acid oxidation, and gluconeogenesis. In addition, the cytochrome P450 enzymes, particularly CYP2E1, contribute to the oxidation of alcohol to acetaldehyde, particularly at increasing alcohol concentrations as well as following their induction by chronic alcohol abuse. Because CYP2E1 is involved in oxidation of several drugs to their reactive intermediates (e.g., nitrosamines, acetaminophen, and halothane), their toxicity is enhanced in alcoholics. This pathway of alcohol oxidation results in the production of large amounts of reactive oxygen species (ROS) and is thought to be an important mechanism contributing to alcoholic liver injury. ROS are eliminated by antioxidants like glutathione (GSH) under normal conditions. Alcohol depletes cellular GSH stores, thereby further exacerbating ROS-mediated injury. ROS can interact with lipids, producing lipid peroxidation, leading to formation of reactive molecules such as malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE), which can in turn form protein adducts. A minor fraction of alcohol metabolism occurs in peroxisomes through catalase-dependent oxidation. Alcohol can also react with glucuronic acid to form ethyl-glucuronide, a soluble, non-volatile conjugate that is readily excreted and detected in body fluids, tissue, sweat, and hair for an extended time following alcohol consumption. Published in: Patricia E. Molina; Jason D. Gardner; Flavia M. Souza-Smith; Annie M. Whitaker; Physiology  2014, 29, 203-215. Copyright © 2014 The International Union of Physiological Sciences and The American Physiological Society