Families of retinoid dehydrogenases regulating vitamin A function
Production of visual pigment and retinoic acid
Article first published online: 25 DEC 2001
European Journal of Biochemistry
Volume 267, Issue 14, pages 4315–4324, July 2000
How to Cite
Duester, G. (2000), Families of retinoid dehydrogenases regulating vitamin A function. European Journal of Biochemistry, 267: 4315–4324. doi: 10.1046/j.1432-1327.2000.01497.x
- Issue published online: 25 DEC 2001
- Article first published online: 25 DEC 2001
- (Received 28 February 2000, revised 25 April 2000, accepted 22 May 2000)
- retinoid metabolism;
- retinoic acid;
- alcohol dehydrogenase;
- aldehyde dehydrogenase;
- short-chain dehydrogenase/reductase.
Vitamin A (retinol) and provitamin A (β-carotene) are metabolized to specific retinoid derivatives which function in either vision or growth and development. 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 receptors that regulate gene expression only in chordate animals. Investigation of retinoid metabolic pathways has resulted in the identification of numerous retinoid dehydrogenases that potentially contribute to metabolism of various retinoid isomers to produce active forms. These enzymes fall into three major families. Dehydrogenases catalyzing the reversible oxidation/reduction of retinol and retinal are members of either the alcohol dehydrogenase (ADH) or short-chain dehydrogenase/reductase (SDR) enzyme families, whereas dehydrogenases catalyzing the oxidation of retinal to retinoic acid are members of the aldehyde dehydrogenase (ALDH) family. Compilation of the known retinoid dehydrogenases indicates the existence of 17 nonorthologous forms: five ADHs, eight SDRs, and four ALDHs, eight of which are conserved in both mouse and human. Genetic studies indicate in vivo roles for two ADHs (ADH1 and ADH4), one SDR (RDH5), and two ALDHs (ALDH1 and RALDH2) all of which are conserved between humans and rodents. For several SDRs (RoDH1, RoDH4, CRAD1, and CRAD2) androgens rather than retinoids are the predominant substrates suggesting a function in androgen metabolism as well as retinoid metabolism.