Since these initial discoveries, much has been learned about alcohol metabolism. Ethanol metabolism occurs predominantly in the liver in two steps: the oxidation of ethanol to acetaldehyde catalyzed by alcohol dehydrogenases (ADHs), and the oxidation of acetaldehyde to acetate by acetaldhyde dehydrogenases (ALDHs). Several known genetic variants cause amino acid changes in these proteins and alter enzymatic activity. For instance, ADH1B*2, or rs1229984, diminishes ADH1b enzymatic activity several fold, and ALDH2*2, or rs671, results in a nearly inactive enzyme (Edenberg, 2007). These genetic variants reduce the probability of heavy alcohol consumption and the development of alcohol dependence (Edenberg, 2007; Macgregor et al., 2009; Sherva et al., 2009). The mechanism by which variants of these enzymes influence the risk of developing alcohol dependence is hypothesized to be through an elevation of acetaldehyde levels after drinking, leading to facial flushing, nausea, and other adverse reactions.
