17beta-Hydroxysteroid dehydrogenase type 9 and other short-chain dehydrogenases/reductases that catalyze retinoid, 17beta- and 3alpha-hydroxysteroid metabolism.
Subgroups of related short-chain dehydrogenase/reductase (SDR) family members serve as retinoid/androgen/estrogen metabolizing enzymes. These include retinol dehydrogenases (RoDHs) 1-3, cis-retinol/androgen dehydrogenase 1 and 2 (CRAD), retSDRs1-4, 9/11-cis-retinol dehydrogenase, and 17beta-hydroxysteroid dehydrogenase (17beta-HSD) types 6 and 9. Interaction with cellular retinol-binding protein (CRBP), the major physiological form of retinol, led to the identification and cDNA cloning of RoDH1. Probes for RoDH1 contributed to cDNA cloning many of the others. Some of these SDRs show specificity with all-trans-retinol (RoDH, retSDR, 17beta-HSD6 and 9) and others with 9 and/or 11-cis-retinol (CRAD, 9/11-cis-retinol dehydrogenase). Many have 3alpha-HSD activities with 3alpha-androstandiol as the most efficiently used substrate, followed by androsterone. In addition to 3alpha-HSD activity, CRAD2 shows relatively weak 17beta-HSD activity with testosterone. Rat 17beta-HSD6 and mouse 17beta-HSD9, which are not interspecies homologs, have efficient 17beta-HSD activities. 17beta-HSD6 has approximately 50% greater 17beta-HSD activity with estradiol than with 3alpha-androstandiol. With 3alpha-androstandiol, 17beta-HSD9 operates equally efficiently as a 17beta-HSD or a 3alpha-HSD. The multi-substrate nature of these SDRs allows for retinoid/steroid interactions. The ability of some these SDRs to access retinol bound with CRBP provides specificity in retinoid metabolism and allows retinoic acid biosynthesis and retinol esterification to continue, as CRBP protects retinol from the general cellular milieu.
Napoli
J L
JL
Department of Nutritional Sciences and Toxicology, 119 Morgan Hall, University of California, Berkeley, CA 94720-3104, USA. jna@uclink4.berkeley.edu
D015067:17-Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D017124:Conserved Sequence; D006801:Humans; D006914:Hydroxysteroids / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D012176:Retinoids / Q000378:metabolism*; D017385:Sequence Homology
D006914:Hydroxysteroids; D007527:Isoenzymes; D012176:Retinoids; D015067:17-Hydroxysteroid Dehydrogenases