Ethanol and related alcohols can be ingested as part of the diet and are formed by microorganisms in the intestinal tract. Ethanol oxidation to acetate occurs primarily in liver cells in a multistep process first described by Racker (1949). First, in the cytosol, ethanol is oxidized to acetaldehyde, with the formation of NADH. Second, in the mitochondrion, acetaldehyde is oxidized to acetate with the formation of NADH. Finally, acetate in the mitochondrion can be condensed with coenzyme A to form acetyl CoA. Polymorphisms in the enzymes catalyzing the first two steps are associated with variation in the efficiency of alcohol catabolism in human populations (Chen et al. 1999; Lange et al. 1976; Jornvall 1985). The molecular mechanism by which cytosolic acetaldehyde enters the mitochondrial matrix is not known (Lemasters 2007).
Cytosolic enzymes capable of oxidizing acetaldehyde to acetate have also been identified and characterized in vitro (Inoue et al. 1979) so a purely cytosolic pathway for ethanol oxidation to acetate and conversion to acetyl-CoA can be annotated. The role of this pathway in vivo is unclear, though limited attempts to correlate deficiencies in the cytosolic enzyme with alcohol intolerance have yielded suggestive data (Yoshida et al. 1989). Additional peroxisomal and microsomal pathways for the oxidation of ethanol to acetaldehyde have been described; their physiological significance is unclear and they are not annotated here.