The major metabolic consequence of ethanol metabolism is the production of the highly reactive molecule acetaldehyde, which can form adducts on proteins in the liver, causing damage and inflammation that can ultimately lead to necrosis (7). As the efficiency of ALDH to oxidize acetaldehyde to acetate is greater than the efficiency of ADH to produce acetaldehyde, the levels of acetaldehyde in the liver and circulating in the blood are generally kept low. With chronic alcohol consumption, however, the efficiency of ALDH is impaired and aldehyde oxidation is decreased, leading to higher levels of circulating acetaldehyde and thus an increase in acetaldehyde adducts. This build-up of acetaldehyde adducts with thiol and amino groups in proteins can inhibit the function of these proteins as well as cause an inflammatory immune response. Accumulated acetaldehyde also acts as an inhibitor of ADH, which will impede the effective elimination of alcohol from the body (3).
There are 19 isozymes of aldehyde dehydrogenase, with ALDH2 specific to acetaldehyde oxidation. The catalytic reaction occurs in five steps: first Cys-302 is activated by a water-mediated proton abstraction by Glu-268, then the thiolate group of Cys-302 attacks the electrophilic aldehyde which forms a tetrahedral thiohemiacetal intermediate and a hydride transfer to the NAD+ ring, resulting in a thioester intermediate which is hydrolyzed, followed by the dissociation of NADH and regeneration of the enzyme due to NAD+ binding (11).