Ethanol is absorbed from the gastrointestinal tract, primarily in the small intestine, then travels to the liver, and from there is distributed throughout the body water (Hurley et al., 2002). The first step in the major pathway of its metabolism is oxidation to acetaldehyde by alcohol dehydrogenases (ADHs) (Figure 1). Metabolism by cytochrome P450s and catalase make only minor contributions (Hurley et al., 2002). Acetaldehyde binds readily to proteins, RNA and DNA, and can be aversive and toxic (Zakhari, 2006). Acetaldehyde is rapidly oxidized to acetate by aldehyde dehydrogenases (ALDHs). First pass metabolism (metabolism before the ethanol reaches the general circulation) occurs in the digestive tract and on its first pass from there through the liver. From then on, most metabolism occurs in the liver, catalyzed by ADH and ALDH enzymes1. Levels of ethanol can get high: the blood alcohol concentration that is defined as legal intoxication in the US (0.08%) corresponds to 17 mM ethanol. The oxidation of acetaldehyde is extremely efficient, such that circulating levels of acetaldehyde are usually more than 1000-fold less; they are generally barely detectable,
