hydroxysteroid 17-beta dehydrogenase 6 (17-beta-HSD6, oxidative 3-alpha hydroxysteroid dehydrogenase, 3-alpha->beta-hydroxysteroid epimerase, 3-alpha->beta-HSE, HSD17B6, RODH)
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Function
- NAD-dependent oxidoreductase with broad substrate specificity
- shows both oxidative & reductive activity (in vitro)
- has 17-beta-hydroxysteroid dehydrogenase activity towards various steroids (in vitro)
- converts 5-alpha-androstan-3-alpha,17-beta-diol to androsterone & estradiol to estrone (in vitro)
- 3-alpha-hydroxysteroid dehydrogenase activity towards androsterone (in vitro)
- has retinol dehydrogenase activity towards all-trans-retinol (in vitro)
- can convert androsterone to epi-androsterone
- androsterone is first oxidized to 5-alpha-androstane-3,17-dione & then reduced to epi-andosterone
- can act on both C-19 & C-21 3-alpha-hydroxysteroids
estradiol-17-beta + NAD+/NADP+ <--> estrone + NADH/NADPH
testosterone + NAD+ <--> androst-4-ene-3,17-dione + NADH
retinol + NAD+ <--> retinal + NADH
- KM=0.19 uM for NAD
- KM=0.18 uM for NADH
- KM=54 uM for NADPH
- KM=940 uM for NADP
- KM=3.2 uM for all-trans-retinol
- KM=0.24 uM for allopregnanolone
- KM=0.13 uM for 3-alpha-androstanediol
- KM=0.23 uM for androsterone
- KM=0.13 uM for dehydroepiandrosterone
- Vmax=1.2 nmol/min/mg enzyme with all-trans-retinol
- Vmax=14.7 nmol/min/mg enzyme with allopregnanolone
- Vmax=16.5 nmol/min/mg enzyme with 3-alpha-androstanediol
- Vmax=35 nmol/min/mg enzyme with androsterone
- Vmax=0.90 nmol/min/mg enzyme with dehydroepiandrosterone
Structure
- belongs to the short-chain dehydrogenases/reductases (SDR) family
Compartment
Expression
- detected in liver & prostate (at protein level)
- detected in adult liver, lung, brain, placenta, prostate, adrenal gland, testis, mammary gland, spleen, spinal cord & uterus.
- detected in caudate nucleus, & at lower levels in amygdala, corpus callosum, hippocampus, substantia nigra & thalamus
- detected in fetal lung, liver & brain
Notes
- kinetic parameters determined using microsomes from transfected cells