Aldehyde dehydrogenase 1 family member A1 and Aldehyde dehydrogenase 2 (ALDH1A1 / ALDH2)

Aldehyde dehydrogenase 1A1 (ALDH1A1) and Aldehyde dehydrogenase 2 (ALDH2) are key enzymes in the aldehyde dehydrogenase superfamily that catalyze the NAD(P)+-dependent oxidation of aldehydes into carboxylic acids. ALDH1A1 is a cytosolic enzyme primarily known for its role in converting retinaldehyde to retinoic acid, a critical signaling molecule for cell differentiation and the maintenance of cancer stem cells. ALDH2 is a mitochondrial enzyme and the primary catalyst for the detoxification of acetaldehyde, the toxic intermediate of ethanol metabolism, and it also protects against oxidative stress by metabolizing reactive lipid peroxidation products like 4-hydroxynonenal. These enzymes are significant therapeutic targets; ALDH2 inhibition is a classic strategy for treating alcohol use disorder by inducing a sensitivity to alcohol, while ALDH2 activation is being investigated for cardioprotection during ischemia-reperfusion injury. In oncology, ALDH1A1 is targeted to eliminate chemoresistant cancer stem cell populations and sensitize tumors to traditional therapies like cyclophosphamide.

Other names

Retinaldehyde dehydrogenase 1RALDH1Mitochondrial aldehyde dehydrogenaseALDH-MALDH-E1ALDCPUMB13-deoxyglucosone dehydrogenaseLiver cytosolic aldehyde dehydrogenase

Irreversible inhibition, reversible inhibition, allosteric activation, and competitive inhibition