in the nucleus but have leader sequences that direct them to cell components called mitochondria, where they exert their functions in the mitochondrial interior (i.e., the matrix) (Jackson et al. 2011). Of the three isoenzymes, ALDH2 seems to carry out most of the oxidation of ethanol-derived acetaldehyde, as demonstrated by the effects of its inhibition by activated forms of the medication disulfiram (Antabuse®) and by the effects of a functional polymorphism commonly found in East Asian populations (ALDH2*2), in which a critical glutamate is substituted by a lysine residue at position 504 of the precursor protein (487 of the mature protein) (ALDH2-Lys504; rs671) (Hurley et al. 2002). With both disulfiram and the ALDH2*2 enzyme, ALDH2 activity is severely compromised, resulting in increased levels of acetaldehyde, which enters the systemic circulation and initiates the commonly observed facial flushing syndrome. In vitro kinetic analyses also are consistent with the key role of ALDH2, demonstrating that the ALDH2 isoenzyme has the highest catalytic efficiency for acetaldehyde oxidation (Hurley et al. 2002). The ALDH2*2 allele is relatively common in East Asia (frequencies of 12 to 41 percent [Li et al. 2009]), where it has a very strong effect on risk for alcoholism. Thus, people
