title: Differences in susceptibility to inactivation of human aldehyde dehydrogenases by lipid peroxidation byproducts.
abstract: Aldehyde dehydrogenases (ALDHs) are involved in the detoxification of aldehydes generated as byproducts of lipid peroxidation. In this work, it was determined that, among the three most studied human ALDH isoforms, ALDH2 showed the highest catalytic efficiency for oxidation of acrolein, 4-hydroxy-2-nonenal (4-HNE), and malondialdehyde. ALDH1A1 also exhibited significant activity with these substrates, whereas ALDH3A1 only showed activity with 4-HNE. ALDH2 was also the most sensitive isoform to irreversible inactivation by these compounds. Remarkably, ALDH3A1 was insensitive to these aldehydes even at concentrations as high as 20 mM. Formation of adducts of ALDH1A1 and ALDH2 with acrolein increased their K(d) values for NAD(+) by 2- and 3-fold, respectively. NADH exerted a higher protection than propionaldehyde to the inactivation by acrolein, and this protection was additive. These results suggested that both binding sites, those for aldehyde and NAD(+) in ALDH2, are targets for the inactivation by lipid peroxidation products. Thus, with the advantage of being relatively inactivation-insensitive, ALDH1A1 and ALDH3A1 may be actively participating in the detoxification of these aldehydes in the cells.
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, México DF, México.
authors.forename: Belem
authors.initials: B
authors.lastname: Yoval-Sánchez
authors.forename: José S
authors.initials: JS
authors.lastname: Rodríguez-Zavala
mesh_terms: D000171:Acrolein / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000447:Aldehydes / Q000378:metabolism*; D000595:Amino Acid Sequence; D006801:Humans; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism*; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D050697:Retinal Dehydrogenase; D016415:Sequence Alignment
chemical_list: D000447:Aldehydes; D011994:Recombinant Proteins; D008315:Malondialdehyde; D000171:Acrolein; D000080924:Aldehyde Dehydrogenase 1 Family; C096127:ALDH2 protein, human; C480021:ALDH3A1 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; C027576:4-hydroxy-2-nonenal