Aldehyde dehydrogenase 1 and aldehyde dehydrogenase 2 (ALDH1 and ALDH2)

ALDH1 and ALDH2 are members of the aldehyde dehydrogenase enzyme superfamily responsible for the NAD(P)+-dependent oxidation of a wide range of aldehydes to carboxylic acids, a critical step in detoxification and metabolism[2][3][6]. ALDH2 is mainly localized in mitochondria and has a pivotal role in the metabolism of acetaldehyde, the toxic intermediate of alcohol catabolism; individuals carrying inactivating mutations (notably the ALDH2*2 allele) experience "Asian flush," higher acetaldehyde exposure, and are at increased risk for certain cancers and cardiovascular conditions[2][4]. ALDH1 comprises several isoforms, mainly cytosolic, with major roles in retinoic acid synthesis (crucial for development) and chemoresistance in cancer stem cells[3][4]. Both are tetrameric enzymes with homologous structural folds but differ in active site channel size, conferring substrate specificity: ALDH2 prefers small aldehydes like acetaldehyde, while ALDH1 isoforms can process bulkier substrates like retinaldehyde[1][3][5]. ALDH enzymes also interact with several drugs, including disulfiram and nitroglycerin, and their expression/activity serve as useful disease and stemness biomarkers[2][4][6].

Other names

ALDH1A1 (cytosolic form of ALDH1)ALDH1A2, ALDH1A3 (isoforms of ALDH1)Mitochondrial aldehyde dehydrogenase (ALDH2)Aldehyde dehydrogenase (general, for the enzyme family)

Inhibition of enzyme (Disulfiram and cyanamide inhibit ALDH, causing build-up of acetaldehyde) - Activation or stabilization of mutated or inactive enzyme (Alda-1 restores ALDH2 activity in mutant forms) - Bioactivation of prodrugs (ALDH2 converts nitroglycerin to active metabolites)