Aldehyde dehydrogenase 2 (ALDH2) (ALDH2)

Aldehyde dehydrogenase 2 (ALDH2) is a key mitochondrial enzyme primarily responsible for the oxidation of acetaldehyde, a toxic intermediate of ethanol metabolism, into acetic acid (UniProt: P05091). It plays a crucial role in the detoxification of various endogenous and exogenous aldehydes, thereby protecting cells from oxidative stress and DNA damage (PubMed: 28395101). In the context of disease, a common genetic variant (ALDH2*2) leads to enzyme deficiency, resulting in alcohol hypersensitivity and an increased risk of esophageal and head and neck cancers (NIH: Genetic Testing for ALDH2). ALDH2 is the primary therapeutic target of disulfiram, a drug used to treat alcohol use disorder by causing an accumulation of acetaldehyde, which triggers a highly unpleasant physiological response (StatPearls: Disulfiram). Additionally, ALDH2 is involved in the metabolic activation of the anti-anginal drug nitroglycerin and has been investigated for its protective roles in cardiovascular and neurodegenerative conditions (PubMed: 24636455).

Other names

ALDH-E2ALDMAldehyde dehydrogenase, mitochondrialALDH2

Irreversible inhibition of the enzyme's catalytic activity through covalent binding to the active site cysteine residue (Cys302), preventing the oxidation of acetaldehyde to acetate.