Aldehyde Dehydrogenase (ALDH)

Aldehyde Dehydrogenases (ALDHs) are a superfamily of NADP⁺-dependent enzymes that metabolize endogenous and exogenous aldehydes to corresponding carboxylic acids. This superfamily of proteins is comprised of 19 isozymes, with constitutive activity of at least one isozyme observed in a majority of mammalian tissues. The ALDHs play important roles, among other things, in cellular detoxification, the protection against ultraviolet radiation-induced damage, and amino acid metabolism.

The ALDH1A subfamily plays a pivotal role in embryogenesis and development by mediating retinoic acid signaling. ALDH2, as a key enzyme that oxidizes acetaldehyde, is crucial for alcohol metabolism. ALDH1A1 and ALDH3A1 are lens and corneal crystallins, which are essential elements of the cellular defense mechanism against ultraviolet radiation-induced damage in ocular tissues. Many ALDH isozymes are important in oxidizing reactive aldehydes derived from lipid peroxidation and thereby help maintain cellular homeostasis. Increased expression and activity of ALDH isozymes have been reported in various human cancers and are associated with cancer relapse. As a direct consequence of their significant physiological and toxicological roles, inhibitors of the ALDH enzymes have been developed to treat human diseases.