AB049. Aldehyde dehydrogenases: from cancer stem cells to inborn errors of metabolism

Abstract: The aldehyde dehydrogenase (ALDH) superfamily comprises NADP-dependent enzymes that catalyze the oxidation of aldehydes to their corresponding carboxylic acids. To date, 19 ALDH genes have been identified in the human genome. In addition to aldehyde metabolizing capacity, ALDHs have additional catalytic (e.g., esterase and reductase) and non-catalytic activities. The latter include functioning as structural elements in the eye (crystallins) and as binding molecules to endobioticsand xenobiotics. Mutations in human ALDH genes are the molecular basis of several diseases, including gamma-hydroxybutyricaciduria, type II hyperprolinemia, Sjögren-Larsson syndrome, pyridoxine-dependent epilepsy as well as osteoporosis and gout. ALDH enzymes also play important roles in embryogenesis and development, neurotransmission, oxidative stress and cancer. One of the most exciting recent discoveries regarding ALDHs is their identification as markers of cancer stem cells and their involvement in cancer cell resistance to chemotherapy and radiotherapy. Thus, therapeutic targeting of ALDHs may represent a novel means of more effectively treating patients with cancer or metabolic disease and improving clinical outcomes.

Keywords: Aldehyde dehydrogenase genes (ALDH genes); target therapy; inborn errors of metabolism