Update on the aldehyde dehydrogenase gene (ALDH) superfamily

The aldehyde dehydrogenase gene (ALDH) superfamily is represented in all three taxonomic domains (Archaea, Eubacteria and Eukarya), suggesting a vital role throughout evolutionary history. Our understanding of the biological roles of this superfamily continues to expand in ways that are often unexpected and, perhaps, unprecedented for an enzyme family. As implied by their name, members of this superfamily serve to metabolise both physiologically and pathophysiologically relevant aldehydes. This capacity prevents the accumulation of toxic aldehydes derived from endogenous production and/or exogenous exposures, which, if left unchecked, adversely affect cellular homeostasis and organismal functions [1].ALDH activity is also required for the synthesis of vital biomolecules through the metabolism of aldehyde intermediates, such as retinoic acid, folate and betaine, to name a few [2-4]. Whereas the ability of the ALDH family members to metabolise reactive aldehydes represents a major underlying cytoprotective mechanism, it is important to recognise that ALDHs demonstrate functions that extend beyond detoxification. Accumulating evidence supports roles for ALDHs in the modulation of cell proliferation, differentiation and survival, especially through participation in retinoic acid synthesis [2]. Members of this superfamily also exhibit functions that appear to be independent of their enzyme activity, including absorption of ultraviolet (UV) irradiation in the cornea by acting as a crystallin and binding to hormones and other small molecules, including androgens, cholesterol, thyroid hormone and acetaminophen [2,5,6].Sequencing of the human genome and subsequent identification of mutations in ALDH genes associated with loss of ALDH enzyme activity have led to the identification of many disease associations, such as cataracts (ALDH1A1, ALDH3A1, ALDH18A1), seizures (ALDH7A1), hyperprolinaemia (ALDH4A1), heart disease (ALDH2), alcohol sensitivity (ALDH1A1, ALDH1B1, ALDH2), ce