ALDH2

Mitochondrial aldehyde dehydrogenase with broad substrate specificity which participates in the detoxification of ethanol-derived acetaldehyde and endogenous aldehydes, including those arising from lipid peroxidation. The reaction mechanism involves a nucleophilic attack on the aldehyde substrate, resulting in formation of a thiohemiacetal intermediate. Subsequent hydride transfer to NAD+, yields a thioester intermediate which is hydrolyzed to the carboxylic acid product through activation of a water molecule by the catalytic glutamate. In vivo, ALDH2 is required for the clearance of formaldehyde, a cytotoxic and carcinogenic endogenous metabolite that induces DNA damage. It also catalyzes the oxidation of 3,4-dihydroxyphenylacetaldehyde (DOPAL), a reactive intermediate of dopamine catabolism, to 3,4-dihydroxyphenylacetate (DOPAC). ALDH2 may also catalyze the oxidation of 4-aminobutanal (gamma-aminobutyraldehyde) to 4-aminobutanoate (GABA), representing an alternative route for GABA biosynthesis from polyamine catabolism (By similarity). In vitro, ALDH2 catalyzes the oxidation of acrolein, malondialdehyde, and 4-hydroxynonenal (4-HNE). It also exhibits esterase activity that is enhanced by NAD+ but does not require it, although the physiological relevance of this activity remains unclear..

Function from UniProtKB (P05091), read 2026-09-23. CC BY 4.0.