Structure and function of retinol dehydrogenases of the short chain dehydrogenase/reductase family

Abstract

All-trans-retinol is the common precursor of the active retinoids 11-cis-retinal, all-trans-retinoic acid (atRA) and 9-cis-retinoic acid (9cRA). Genetic and biochemical data supports an important role of the microsomal members of the short chain dehydrogenases/reductases (SDRs) in the first oxidative conversion of retinol into retinal. Several retinol dehydrogenases of this family have been reported in recent years. However, the structural and functional data on these enzymes is limited. The prototypic enzyme RDH5 and the related enzyme CRAD1 have been shown to face the lumen of the endoplasmic reticulum (ER), suggesting a compartmentalized synthesis of retinal. This is a matter of debate as a related enzyme has been proposed to have the opposite membrane topology. Recent data indicates that RDH5, and presumably other members of the SDRs, occur as functional homodimers, and need to interact with other proteins for proper intracellular localization and catalytic activity. Further analyses on the compartmentalization, membrane topology, and functional properties of microsomal retinol dehydrogenases, will give important clues about how retinoids are processed.