Aldehyde dehydrogenase 2 (mitochondrial) (ALDH2) (ALDH2)

Aldehyde dehydrogenase 2 (ALDH2) is a vital mitochondrial enzyme that catalyzes the second step of ethanol metabolism, converting toxic acetaldehyde into acetate (UniProt: P05091). Beyond its role in alcohol processing, ALDH2 is essential for the detoxification of endogenous reactive aldehydes, such as 4-hydroxynonenal (4-HNE), which are generated during lipid peroxidation and oxidative stress (PubMed: 24603265). A common genetic variant, ALDH2*2, results in a nearly inactive enzyme and is highly prevalent in East Asian populations, leading to the alcohol flushing syndrome and increased risks for esophageal cancer and cardiovascular diseases (NIH: PMC3641551). Pharmacologically, ALDH2 is a well-established target for disulfiram, an inhibitor used to treat alcohol use disorder by inducing aversive symptoms upon alcohol ingestion (StatPearls: NBK459340). Recent therapeutic interest has shifted toward ALDH2 activators, such as Alda-1, which are being explored for their potential to protect against myocardial infarction, stroke, and neurodegeneration by enhancing the clearance of toxic metabolic byproducts (PubMed: 18787169).

Other names

ALDH-E2ALDH class 2Mitochondrial aldehyde dehydrogenaseALDH-2ALDM

Inhibition of ALDH2 leads to the accumulation of acetaldehyde, causing aversive physiological reactions to deter alcohol consumption; activation of ALDH2 enhances the detoxification of reactive aldehydes to reduce oxidative damage in tissues (StatPearls: NBK459340, PubMed: 18787169).