title: Alcohol and aldehyde dehydrogenases: retinoid metabolic effects in mouse knockout models.
abstract: Retinoic acid (RA) is the active metabolite of vitamin A (retinol) that controls growth and development. The first step of RA synthesis is controlled by enzymes of the alcohol dehydrogenase (ADH) and retinol dehydrogenase (RDH) families that catalyze oxidation of retinol to retinaldehyde. The second step of RA synthesis is controlled by members of the aldehyde dehydrogenase (ALDH) family also known as retinaldehyde dehydrogenase (RALDH) that further oxidize retinaldehyde to produce RA. RA functions as a ligand for DNA-binding RA receptors that directly regulate transcription of specific target genes. Elucidation of the vitamin A metabolic pathway and investigation of the endogenous function of vitamin A metabolites has been greatly improved by development of mouse ADH, RDH, and RALDH loss-of-function models. ADH knockouts have demonstrated a postnatal role for this enzyme family in clearance of excess retinol to prevent vitamin A toxicity and in generation of RA for postnatal survival during vitamin A deficiency. A point mutation in Rdh10 generated by ethylnitrosourea has demonstrated that RDH10 generates much of the retinaldehyde needed for RA synthesis during embryonic development. Raldh1, Raldh2, and Raldh3 knockouts have demonstrated that RALDH1, RALDH2, and RALDH3 generate most of the RA needed during embryogenesis. These mouse models serve as instrumental tools for providing new insight into retinoid function. This article is part of a Special Issue entitled: Retinoid and Lipid Metabolism.
authors.affiliation: Sanford-Burnham Medical Research Institute, Development and Aging Program, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Sandell
authors.forename: Paul A
authors.initials: PA
authors.lastname: Trainor
authors.forename: Frank
authors.initials: F
authors.lastname: Koentgen
authors.forename: Gregg
authors.initials: G
authors.lastname: Duester
mesh_terms: D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D014212:Tretinoin; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase