Stereospecificity of Retinol Saturase: Absolute Configuration, Synthesis, and Biological Evaluation of Dihydroretinoids

摘要

Mouse RetSat catalyzes the saturation of the C13-C14 double bond of all-frans-retinol to produce all-trarcs-13,14-dihydroretinol 8 (Figure 1). A related enzyme in zebrafish catalyzes the saturation of the C7-C8 double bond in addition to the C13-C14 double bond of all-fraras-retinol to produce both 8 and all-trans-7,8-dihydroretinol. Further oxidation of 8 and of all-frans-7,8-dihydroretinol by retinol dehydrogenases and then by retinaldehyde dehydrogenase enzymes leads to formation of all-tran.y-13,14-dihydroretinoic acid 9 and all-tran.s-7,8-dihydroretinoic acid, compounds whose levels are exquisitely controlled in vivo by the enzymes that catalyze their synthesis and breakdown.