Update on the aldehyde dehydrogenase gene (ALDH) superfamily

Abstract

Members of the aldehyde dehydrogenase gene (ALDH) superfamily play an important role in the enzymic detoxification of endogenous and exogenous aldehydes and in the formation of molecules that are important in cellular processes, like retinoic acid, betaine and gamma-aminobutyric acid. ALDHs exhibit additional, non-enzymic functions, including the capacity to bind to some hormones and other small molecules and to diminish the effects of ultraviolet irradiation in the cornea. Mutations in ALDH genes leading to defective aldehyde metabolism are the molecular basis of several diseases, including gamma-hydroxybutyric aciduria, pyridoxine-dependent seizures, Sjögren–Larsson syndrome and type II hyperprolinaemia. Interestingly, several ALDH enzymes appear to be markers for normal and cancer stem cells. The superfamily is evolutionarily ancient and is represented within Archaea, Eubacteria and Eukarya taxa. Recent improvements in DNA and protein sequencing have led to the identification of many new ALDH family members. To date, the human genome contains 19 known ALDH genes, as well as many pseudogenes. Whole-genome sequencing allows for comparison of the entire complement of ALDH family members among organisms. This paper provides an update of ALDH genes in several recently sequenced vertebrates and aims to clarify the associated records found in the National Center for Biotechnology Information (NCBI) gene database. It also highlights where and when likely gene-duplication and gene-loss events have occurred. This information should be useful to future studies that might wish to compare the role of ALDH members among species and how the gene superfamily as a whole has changed throughout evolution.

Glutathione peroxidase 3, a new retinoid target gene, is crucial for human skeletal muscle precursor cell survival

“…Aldehyde dehydrogenases (ALDHs) efficiently oxidize and detoxify aldehydic products of lipid peroxidation (LPO) initially generated by reactive oxygen species (Jackson et al, 2011) and contribute to stem cell self-protection, differentiation and/or selfrenewal (Balber, 2011;Ma and Allan, 2011). Recently, we determined that high aldehyde dehydrogenase activity (ALDH high ) is associated with improved cell viability in human myoblasts (Jean et al, 2011).…”

Diabetes-related adduct formation and retinopathy

“…At least 19 ALDH isozymes have been identified localized to several cellular compartments and displaying Fig. 1 The structures of lipoxidation-derived reactive carbonyl species and the principal advanced lipoxidation adducts formed following their reaction with proteins varying affinities to a wide range of aldehyde substrates [90]. In addition to ALDH, other enzymes with high selectivity towards specific aldehydes have also been shown to play a detoxification role.…”

The Glu504Lys Polymorphism of Aldehyde Dehydrogenase 2 Contributes to Development of Coronary Artery Disease

“…ALDH is an enzyme superfamily in human body that is responsible for the detoxification of biogenic and xenogenic aldehydes, including the alcohol-derived aldehyde, in various organs and cells (Jackson et al 2011). Alcohol in the body is catalyzed by alcohol dehydrogenase into aldehyde, which is then converted to acetic acid by ALDH.…”