Families of retinoid dehydrogenases regulating vitamin A function - Production of visual pigment and retinoic acid

Vitamin A (retinol) and provitamin A (beta-carotene) are metabolized to spe cific retinoid derivatives which function in either vision or growth and de velopment. The metabolite 11-cis-retinal functions in light absorption for vision in chordate and nonchordate animals, whereas all-trans-retinoic acid and 9-cis-retinoic acid function as ligands for nuclear retinoic acid rece ptors that regulate gene expression only in chordate animals. Investigation of retinoid metabolic pathways has resulted in the identification of numer ous retinoid dehydrogenases that potentially contribute to metabolism of va rious retinoid isomers to produce active forms. These enzymes fall into thr ee major families. Dehydrogenases catalyzing the reversible oxidation/reduc tion of retinol and retinal are members of either the alcohol dehydrogenase (ADH) or short-chain dehydrogenase/reductase (SDR) enzyme families, wherea s dehydrogenases catalyzing the oxidation of retinal to retinoic acid are m embers of the aldehyde dehydrogenase (ALDH) family. Compilation of the know n retinoid dehydrogenases indicates the existence of 17 nonorthologous form s: five ADHs, eight SDRs, and four ALDHs, eight of which are conserved in b oth mouse and human. Genetic studies indicate in vivo roles for two ADHs (A DH1 and ADH4), one SDR (RDH5), and two ALDHs (ALDH1 and RALDH2) all of whic h are conserved between humans and rodents. For several SDRs (RoDH1, RoDH4, CRAD1, and CRAD2) androgens rather than retinoids are the predominant subs trates suggesting a function in androgen metabolism as well as retinoid met abolism.