Aldehyde dehydrogenase (ALDH) (ALDH)

Aldehyde dehydrogenases (ALDHs) are a superfamily of enzymes that catalyze the NAD(P)+-dependent oxidation of aldehydes to their corresponding carboxylic acids (UniProt: P00352, P05091). They play a critical role in the detoxification of endogenous and exogenous aldehydes, including those derived from ethanol metabolism and lipid peroxidation (PubMed: 23101303). In humans, the ALDH superfamily consists of 19 functional genes, with ALDH1 and ALDH2 being the most extensively studied due to their roles in ethanol metabolism and retinoic acid signaling (StatPearls: NBK545240). ALDH2 is particularly notable for its role in the mitochondrial oxidation of acetaldehyde; a common genetic polymorphism (ALDH2*2) leads to reduced enzyme activity and the "Asian flushing syndrome" (PubMed: 11592817). Beyond metabolism, ALDHs serve as markers for cancer stem cells and are involved in drug resistance, as they can detoxify certain chemotherapeutic agents like cyclophosphamide (PubMed: 19047085). Therapeutic strategies targeting ALDH include inhibitors like disulfiram for alcohol use disorder and potential activators for cardiovascular protection (PubMed: 18787169).

Other names

ALDH superfamilyAldehyde:NAD+ oxidoreductaseAldehyde dehydrogenase family

Drugs targeting ALDH enzymes primarily act through irreversible inhibition to cause the accumulation of toxic acetaldehyde (e.g., disulfiram) (StatPearls: NBK459340), or through activation to enhance the clearance of reactive aldehydes like 4-hydroxynonenal (e.g., Alda-1) (PubMed: 18787169). Additionally, ALDH2 acts as a prodrug activator for nitroglycerin, converting it into nitric oxide (PubMed: 12050675).