Alcohol primarily is metabolized to acetaldehyde in an oxidation reaction that is mediated (i.e., catalyzed) by enzymes known as alcohol dehydrogenases (ADHs). Other pathways of alcohol oxidation to acetaldehyde involve the enzyme catalase and the microsomal ethanol-oxidizing system (MEOS), whose key component is cytochrome P4502E1 (CYP2E1) (see Agarwal 2001). The acetaldehyde produced in all these reactions is, in turn, metabolized to acetate in a reaction catalyzed by the aldehyde dehydrogenase (ALDH) enzymes. Many of the enzymes involved in alcohol metabolism—several ADHs, CYP2E1, and ALDHs—exist in different, genetically determined forms (i.e., isoforms) that differ in their level of activity. Each person’s rate of alcohol metabolism is determined by the isoforms he or she carries. For example, in a person carrying a less active ADH or CYP2E1 isoform, alcohol is broken down at a relatively slow rate. Conversely, in a person carrying more active isoforms of ADH or CYP2E1, alcohol is broken down at a faster rate, leading to an increased formation of acetaldehyde. Finally, the presence of a less active form of ALDH results in slow acetaldehyde oxidation and the buildup of acetaldehyde in the body following alcohol consumption.
