Oxidative metabolism of alcohol occurs mainly in the liver via a major pathway in which the cytosolic enzyme alcohol dehydrogenase (ADH) produces a highly reactive intermediate, acetaldehyde. In addition to ADH, a group of enzymes, known as cytochrome P450 isozymes (including CYP2E1, 1A2, and 3A4), contribute to the oxidation of alcohol to acetaldehyde in the liver. Acetaldehyde is subsequently metabolized by acetaldehyde dehydrogenase (ALDH) to form acetate, which is eliminated from the body. A catalase-mediated reaction in the peroxisomes is considered a minor pathway for alcohol metabolism in the periphery. In the brain, however, alcohol is metabolized primarily through the activity of catalase. Other metabolic pathways, such as mitochondrial cytochrome P450, also produce acetaldehyde locally within the brain following alcohol consumption (Zakhari, 2013). Acetaldehyde formation mediates the behavioral and neurobiological effects of alcohol, but its role is highly dependent on dose and location (e.g. periphery or brain). For instance, studies have reported that intracranial ventricular administration of acetaldehyde increases ethanol consumption and preference in rodents, while peripheral administration of higher doses of acetaldehyde produces a conditioned taste aversion in several rat lines (reviewed by (Quertemont et al., 2005)).
