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J Biol Chem. 2002 Nov 22;277(47):45537-45546. doi: 10.1074/jbc.M208882200. Epub 2002 Sep 10.

Dual-substrate specificity short chain retinol dehydrogenases from the vertebrate retina.

Author information

Department of Ophthalmology, University of Washington, Seattle, Washington 98195.
Department of Biochemistry, University of Nijmegen, 6500 HB Nijmegen, The Netherlands.
The Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.
Department of Pharmacology, University of Washington, Seattle, Washington 98195.
Department of Chemistry, University of Washington, Seattle, Washington 98195.
Contributed equally


Retinoids are chromophores involved in vision, transcriptional regulation, and cellular differentiation. Members of the short chain alcohol dehydrogenase/reductase superfamily catalyze the transformation of retinol to retinal. Here, we describe the identification and properties of three enzymes from a novel subfamily of four retinol dehydrogenases (RDH11-14) that display dual-substrate specificity, uniquely metabolizing all-trans- and cis-retinols with C(15) pro-R specificity. RDH11-14 could be involved in the first step of all-trans- and 9-cis-retinoic acid production in many tissues. RDH11-14 fill the gap in our understanding of 11-cis-retinal and all-trans-retinal transformations in photoreceptor (RDH12) and retinal pigment epithelial cells (RDH11). The dual-substrate specificity of RDH11 explains the minor phenotype associated with mutations in 11-cis-retinol dehydrogenase (RDH5) causing fundus albipunctatus in humans and engineered mice lacking RDH5. Furthermore, photoreceptor RDH12 could be involved in the production of 11-cis-retinal from 11-cis-retinol during regeneration of the cone visual pigments. These newly identified enzymes add new elements to important retinoid metabolic pathways that have not been explained by previous genetic and biochemical studies.

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