Aldehyde dehydrogenase 2, mitochondrial (ALDH2) (ALDH2)

Aldehyde dehydrogenase 2 (ALDH2) is a critical mitochondrial enzyme primarily located in the liver that catalyzes the oxidation of acetaldehyde into acetate during ethanol metabolism [UniProt: P05091]. It is distinguished by its very low Michaelis constant (Km) for acetaldehyde, ensuring efficient clearance of this toxic intermediate under physiological conditions [PubMed: 20301615]. In addition to its role in alcohol metabolism, ALDH2 is vital for the detoxification of reactive aldehydes like 4-hydroxynonenal (4-HNE) produced during oxidative stress and is involved in the bioactivation of the anti-anginal drug nitroglycerin [PubMed: 15735644]. A prevalent genetic polymorphism, ALDH2*2 (rs671), common in East Asian populations, results in a nearly inactive enzyme, leading to the alcohol flush reaction and an increased risk of gastrointestinal cancers [NIH: GeneID 217]. Therapeutically, ALDH2 is inhibited by drugs like disulfiram to create an aversion to alcohol, while experimental activators like Alda-1 are being explored to treat ischemia-reperfusion injury and other conditions characterized by high oxidative stress [PubMed: 18787169].

Other names

ALDH-E2Mitochondrial aldehyde dehydrogenaseALDH class 2Acetaldehyde dehydrogenase 2ALDMLow-Km mitochondrial aldehyde dehydrogenase

ALDH2 is targeted through two primary pharmacological strategies: irreversible or reversible inhibition (e.g., by disulfiram) to block acetaldehyde metabolism and induce aversive symptoms in alcohol use disorder, and allosteric activation (e.g., by Alda-1) to enhance the clearance of toxic aldehydes and protect tissues from oxidative damage [PubMed: 18787169, StatPearls: Disulfiram].