Description
Aldehyde dehydrogenases (ALDHs) represent a group of enzymes that oxidize a wide range of endogenous and exogenous aldehydes to their corresponding carboxylic acids. Endogenous aldehydes are formed during the metabolism of amino acids, carbohydrates, lipids, biogenic amines, vitamins, and steroids. The human ALDH superfamily comprises 19 isozymes that possess important physiological and toxicological functions. The ALDH1A subfamily plays a pivotal role in embryogenesis and development by mediating retinoic acid signaling. The ALDH2 isozyme is predominantly linked with acetaldehyde detoxification in the second step of alcohol metabolism. The amount of acetaldehyde to which cells or tissues are exposed after alcohol ingestion may be of great importance and may, among others, affect carcinogenesis. ALDH1A1 and ALDH3A1 are lens and corneal crystallins, which are essential elements of the cellular defense mechanism against ultraviolet radiation-induced damage in ocular tissue. ALDH1 activity has been shown to be increased in cancer stem cells and has been used to isolate cancer stem cells in different cancers. Recently, pharmacological inhibitors have been developed for three of the 19 ALDH isozymes. These are the enzymes involved in the metabolism of alcohol (ALDH2) and the anticancer oxazaphophorine drugs (ALDH1A1 and ALDH3A1). Increased or suppressed ALDH activity has been implicated in a variety of diseases, including cancer, Type II hyperprolinemia, Sjögren-Larsson Syndrome, Parkinson"s Disease, Cardiac Disease, and hyperammonemia. Therefore, the application of pharmacological inhibitors or activators of ALDHs represents a rational approach for the treatment of these pathological condition