Information on EC 1.1.1.270 - 3beta-hydroxysteroid 3-dehydrogenase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY
1.1.1.270
-
RECOMMENDED NAME
GeneOntology No.
3beta-hydroxysteroid 3-dehydrogenase
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a 3beta-hydroxysteroid + NADP+ = a 3-oxosteroid + NADPH + H+
show the reaction diagram
stereoselectivity : #1,4,5# catalyzes reduction of the 3-keto group to a 3beta-hydroxyl group <5,6,7>
-
a 3beta-hydroxysteroid + NADP+ = a 3-oxosteroid + NADPH + H+
show the reaction diagram
stereoselectivity : #1,4,5# catalyzes reduction of the 3-keto group to a 3beta-hydroxyl group <5,6,7>
-
a 3beta-hydroxysteroid + NADP+ = a 3-oxosteroid + NADPH + H+
show the reaction diagram
also acts on 5alpha-cholest-7-en-3-one
-
-
-
a 3beta-hydroxysteroid + NADP+ = a 3-oxosteroid + NADPH + H+
show the reaction diagram
residues Leu/Val54, Tyr55, His117, Val128, Ile129, His222, and Trp227 are involved in substrate binding, Tyr55, Asp50, Lys84, and His117 form the catalytic tetrad, Tyr55 and His117 together with NADP+ form an oxyanion hole through hydrogen bond networks, molecular docking simulations, detailed overview
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
oxidation of 3beta-hydroxy-steroids poorly catalyzed for a few substrates
-
redox reaction
-
-
-
-
reduction
-
-
ketone reduction
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
cholesterol biosynthesis I
-
-
cholesterol biosynthesis II (via 24,25-dihydrolanosterol)
-
-
cholesterol biosynthesis III (via desmosterol)
-
-
zymosterol biosynthesis
-
-
cholesterol biosynthesis
-
-
Steroid biosynthesis
-
-
Metabolic pathways
-
-
Biosynthesis of antibiotics
-
-
SYSTEMATIC NAME
IUBMB Comments
3beta-hydroxysteroid:NADP+ 3-oxidoreductase
The enzyme acts on multiple 3beta-hydroxysteroids. Participates in the biosynthesis of zemosterol and cholesterol, where it catalyses the reaction in the opposite direction to that shown. The mammalian enzyme is bifunctional and also catalyses EC 1.1.1.62, 17beta-estradiol 17-dehydrogenase [4].
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
17beta-hydroxysteroid dehydrogenase type 7
-
17beta-hydroxysteroid dehydrogenase type 7
-
3-keto reducing enzyme
-
-
-
-
3-keto reductase
-
-
-
-
3-keto-reductase
-
-
3-ketoreductase
-
-
-
-
3-ketosteroid reductase
-
-
-
-
3-ketosteroid reductase
-
-
3-KSR
-
-
-
-
3-oxo steroid reductase
-
-
-
-
3-oxosteroid reductase
-
-
-
-
3beta-HSD
-
-
3beta-HSD1
-
-
3beta-HSD2
-
-
3beta-hydroxysteroid dehydrogenase
-
-
3beta-hydroxysteroid dehydrogenase type 1
-
-
3beta-hydroxysteroid dehydrogenase/Delta 5->4-isomerase type 1
-
-
3beta-hydroxysteroid dehydrogenase/Delta 5->4-isomerase type 2
-
-
3beta-hydroxysteroid dehydrogenase/isomerase
-
-
AKR1Cs
-
-
aldo-keto reductase 1C2
-
-
reductase, 3-oxo steroid
-
-
-
-
reductive 3beta-HSD
-
-
SDR11E1
-
-
SDR11E2
-
-
steroid-3-ketoreductase
-
-
-
-
sterol 3-ketoreductase
-
-
sterone-reducing enzyme
-
-
-
-
type 3 3alpha-hydroxysteroid dehydrogenase
-
-
CAS REGISTRY NUMBER
COMMENTARY
42616-29-5
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene erg27
-
-
Manually annotated by BRENDA team
var. neoformans, B42419, ATCC 32265, pathogenic fungus
-
-
Manually annotated by BRENDA team
3-ketosteroid reductase activity of the human 3(alpha-beta)-hydroxysteroid epimerase; human
-
-
Manually annotated by BRENDA team
isozymes AKR1C1 and AKR1C2
-
-
Manually annotated by BRENDA team
wild-type
-
-
Manually annotated by BRENDA team
isoform type III of 3beta-hydroxysteroid dehydrogenase/DELTA5-DELTA4 isomerase with almost exclusive 3-ketosteroid reductase activity; male rat
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
zebra finch
-
-
Manually annotated by BRENDA team
maize, variety LG11
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
the rabbit aldose reductase-like protein that shars an 86% sequence identity to human aldo-keto reductase (AKR) 1B10 and is assigned as AKR1B19 in the AKR superfamily. It is bifunctional and also acts as a 3-ketoreductase reducing 3-keto-5alpha/beta-dihydro-C19/C21/C24-steroids into the corresponding 3betahydroxysteroids
evolution
-
human 3beta-hydroxysteroid dehydrogenase is a member of the short-chain dehydrogenase/reductase (SDR) family of enzymes, all of which contain the Rossmann-fold domain with a beta-alpha-beta-alpha-beta-alpha-beta-alpha-beta folding pattern that binds cofactor and substrate
malfunction
-
single and double mutations, F303Q, M304S and F303Q/M304S, significantly impair the 3-ketoreductase activity, suggesting that the two residues play critical roles in recognition of the steroidal substrate
malfunction
-
two Botrytis cinerea fenhexamid-resistant phenotypes both result from mutations in the erg27 gene encoding 3-ketoreductase. Erg27 mutations causing amino acid substitutions in or near the transmembrane domain strongly decrease the affinity of fenhexamid for 3-ketoreductase
metabolism
-
the enzyme catalyzes the first step in the conversion of dehydroepiandrosterone to estradiol
metabolism
-
the 3-ketoreductase is involved at C-4 demethylation steps during ergosterol biosynthesis. Steryl compound contents of Botrytis strains with different fenhexamid susceptibilities, overview
physiological function
-
loss of the 3-keto reductase also results in a concomitant loss of activity of the upstream oxidosqualene cyclase. Oxidosqualene cyclase is not required for the 3-ketoreductase activity. In Saccharomyces cerevisiae, the protective relationship between the 3-keto reductase Erg27 and oxidosqualene cyclase Erg7p is not reciprocal
physiological function
in NS0 cells deficient in 17beta-hydroxysteroid dehydrogenase type 7 activity, oxidosqualene cyclase is fully active. The protective role of the 3-ketoreductase in yeasts with respect to oxidosqualene cyclase activity is not conserved in mammals
physiological function
-
the rabbit aldose reductase-like protein, assigned as AKR1B19, is bifunctional, it shows aldose reductase activity for various aldehydes and alpha-dicarbonyl compounds acting as a defense system against cytotoxic carbonyl compounds in rabbit tissues, and it also acts as a 3-ketoreductase reducing 3-keto-5alpha/beta-dihydro-C19/C21/C24-steroids into the corresponding 3beta-hydroxysteroids
physiological function
-
the enzyme promotes tumor growth in placenta, mammary glands, and breasts. In human adrenals, 3beta-HSD2 is required for the production of cortisol and aldosterone
physiological function
Saccharomyces cerevisiae STY2
-
loss of the 3-keto reductase also results in a concomitant loss of activity of the upstream oxidosqualene cyclase. Oxidosqualene cyclase is not required for the 3-ketoreductase activity. In Saccharomyces cerevisiae, the protective relationship between the 3-keto reductase Erg27 and oxidosqualene cyclase Erg7p is not reciprocal
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(3)H-dehydroepiandrosterone + NAD(P)+
?
show the reaction diagram
-
-
-
-
?
16alpha-hydroxy-dehydroepiandrosterone + NADH + H+
?
show the reaction diagram
-
-
-
-
?
16beta-hydroxy-dehydroepiandrosterone + NADH + H+
?
show the reaction diagram
-
-
-
-
?
17alpha-hydroxypregnenolone + NADH + H+
17alpha-hydroxyprogesterone + NAD+
show the reaction diagram
-
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NADPH
5alpha-androstane-3beta,17beta-diol + NADP+
show the reaction diagram
-
5alpha-dihydrotestosterone
androstanediol
?
17beta-hydroxy-5alpha-androstan-3-one + NADPH
5alpha-androstane-3beta,17beta-diol + NADP+
show the reaction diagram
-
5alpha-dihydrotestosterone
androstanediol
ir
17beta-hydroxy-5alpha-androstan-3-one + NADPH
5alpha-androstane-3beta,17beta-diol + NADP+
show the reaction diagram
-
5alpha-dihydrotestosterone
5alpha-androstane-3alpha,17beta-diol or 5alpha-androstane-3beta,17beta-diol
?
17beta-hydroxy-5alpha-androstan-3-one + NADPH
5alpha-androstane-3beta,17beta-diol + NADP+
show the reaction diagram
-
5alpha-dihydrotestosterone
corresponding 3beta-hydroxysteroid
ir
17beta-hydroxy-5alpha-androstan-3-one + NADPH
5alpha-androstane-3beta,17beta-diol + NADP+
show the reaction diagram
-
DHT
androstanediol
?
17beta-hydroxy-5alpha-androstan-3-one + NADPH
5alpha-androstane-3beta,17beta-diol + NADP+
show the reaction diagram
-
DHT
androstanediol
ir
17beta-hydroxy-5alpha-androstan-3-one + NADPH
5alpha-androstane-3beta,17beta-diol + NADP+
show the reaction diagram
-
DHT
5alpha-androstane-3alpha,17beta-diol or 5alpha-androstane-3beta,17beta-diol
?
17beta-hydroxy-5alpha-androstan-3-one + NADPH
5alpha-androstane-3beta,17beta-diol + NADP+
show the reaction diagram
-
DHT
corresponding 3beta-hydroxysteroid
ir
17beta-hydroxy-5alpha-androstan-3-one + NADPH
5alpha-androstane-3beta,17beta-diol + NADP+
show the reaction diagram
-
dihydrotestosterone
androstanediol
?
17beta-hydroxy-5alpha-androstan-3-one + NADPH
5alpha-androstane-3beta,17beta-diol + NADP+
show the reaction diagram
-
dihydrotestosterone
androstanediol
ir
17beta-hydroxy-5alpha-androstan-3-one + NADPH
5alpha-androstane-3beta,17beta-diol + NADP+
show the reaction diagram
-
dihydrotestosterone
5alpha-androstane-3alpha,17beta-diol or 5alpha-androstane-3beta,17beta-diol
?
17beta-hydroxy-5alpha-androstan-3-one + NADPH
5alpha-androstane-3beta,17beta-diol + NADP+
show the reaction diagram
-
dihydrotestosterone
corresponding 3beta-hydroxysteroid
ir
2 17beta-hydroxy-5alpha-androstan-3-one + 2 NADPH + 2 H+
5alpha-androstane-3beta,17beta-diol + 5alpha-androstane-3alpha,17beta-diol + 2 NADP+
show the reaction diagram
-
the rates of 3alpha-diol versus 3beta-diol formation varies significantly among the isoforms. AKR1C1 predominantly catalyzes the formation of 3beta-diol, whereas AKR1C2 and AKR1C4 predominantly catalyze the formation of 3alpha-diol. AKR1C3 shows relatively low reductive activity towards 17beta-hydroxy-5alpha-androstan-3-one, in which 3alpha-diol and 3beta-diol is formed in almost equal amounts
?
2 17beta-hydroxy-5alpha-androstan-3-one + 2 NADPH + 2 H+
5alpha-androstane-3beta,17beta-diol + 5alpha-androstane-3alpha,17beta-diol + 2 NADP+
show the reaction diagram
AKR1cs are a source of beta-tetrahydrosteroids. This is of physiological significance because the formation of 3beta-diol in contrast to 3alpha-diol is virtually irreversible, the 3beta-diol is a pro-apoptotic ligand for estrogen receptor beta, and 3beta-tetrahydrosteroids act as gamma-aminobutyric acid type A receptor antagonists
-
?
24-ethylidenelophenone + NADPH
24-ethylidenelophenol + NADP+
show the reaction diagram
-
oxidation: poor
-
r
24-methylenecycloartanone + NADPH
24-methylenecycloartanol + NADP+
show the reaction diagram
-
7% compared with cholest-7-en-3-one, DELTA7-cholestenone
-
ir
24-methylenelophenone + NADPH
24-methylenelophenol + NADP+
show the reaction diagram
-
35% compared with cholest-7-en-3-one, DELTA7-cholestenone
-
?
24-methylenepollinastanone + NADPH + acetate
24-methylenepollinastanol + NADP+
show the reaction diagram
-
70% compared with cholest-7-en-3-one, DELTA7-cholestenone
-
?
24RS-dihydrocycloeucalenone + NADPH
24RS-dihydrocycloeucalenol + NADP+
show the reaction diagram
-
53% compared with cholest-7-en-3-one, DELTA7-cholestenone
-
?
3-keto-5alpha-androstane steroids + NADPH
3beta-hydroxy-5alpha-androstane steroids + NADP+
show the reaction diagram
-
-
-
ir
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH
show the reaction diagram
-
-
-
?
3alpha-androstanediol + NAD+
? + NADH
show the reaction diagram
AKR1C2 and AKR1C4 act as 3alpha-hydroxysteroid oxidase, AKR1C3 predominantly acts as 17beta-hydroxysteroid oxidase catalyzing the conversion of 3alpha-diol to androsterone, negligible activity with the 3beta-androstanediol
-
?
4,4-gem-dimethyl-5alpha-cholest-7-en-3-one + NADPH
4,4-gem-dimethyl-5alpha-cholest-7-en-3beta-ol + NADP+
show the reaction diagram
-
-
-
?
4,4-gem-dimethyl-5alpha-cholest-7-en-3-one + NADPH
4,4-gem-dimethyl-5alpha-cholest-7-en-3beta-ol + NADP+
show the reaction diagram
-
-
-
?
4alpha-methyl-5alpha-cholest-7-en-3-one + NADPH
4alpha-methyl-5alpha-cholest-7-en-3beta-ol + NADP+
show the reaction diagram
-
best substrate, reduction consistently about two times greater for monosubstituted steroid
-
?
4alpha-methylfecosterone + NADPH + H+
4alpha-methylfecosterol + NADP+
show the reaction diagram
-
-
4alpha-methylfecosterol is further converted to ergosterol
?
4alpha-methylzymosterol + NADP+
3-dehydro-4-methylzymosterol + NADPH + H+
show the reaction diagram
-
-
-
?
4beta-methyl-28-nor-24RS-dihydrocycloeucalenone + NADPH
4beta-methyl-28-nor-24RS-dihydrocycloeucalenol + NADP+
show the reaction diagram
-
27% compared with cholest-7-en-3-one, DELTA7-cholestenone
-
?
5-androstene-3,17-dione + NAD+
dehydroepiandrosterone + NADH + H+
show the reaction diagram
-
-
-
?
5alpha-androstan-3,17-dione + NADPH + H+
5alpha-androstan-3beta-ol-17-one + NADP+
show the reaction diagram
-
-
-
r
5alpha-androstane-3,17-dione + NADPH
epi-androsterone + NADP+
show the reaction diagram
-
A-dione
-
ir
5alpha-androstane-3,17-dione + NADPH
epi-androsterone + NADP+
show the reaction diagram
-
3-ketosteroid reductase activity of the human 3(alpha-beta)-hydroxysteroid epimerase, stereoselective reduction, 5alpha-dione
epi-ADT
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstan-3alpha,17beta-diol + NADP+
show the reaction diagram
-
i.e. DHT, reductive 3alpha-HSD activity of AKR1C1 yielding the 3alpha,17-diol, low activity
-
?
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
show the reaction diagram
-
in prostate cells AKR1C2 acts as a 3-ketosteroid reductase to eliminate 5alpha-dihydrotestosterone and prevents activation of androgen receptor. AKR1C2 does not act as an oxidase due to either potent product inhibition by NADPH or because it cannot surmount the oxidative 17beta-hydroxysteroid dehydrogenase present. AKR1C2 is not a source of 5alpha-dihydrotestosterone in PC-3 cells
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstan-3beta,17beta-diol + NADP+
show the reaction diagram
-
i.e. DHT, reductive 3beta-HSD activity of AKR1C1 yielding the 3beta,17-diol, preferred reaction
-
?
5alpha-dihydrotestosterone + NADPH + H+
3beta,17beta-dihydroxy-5alpha-androstane + NADP+
show the reaction diagram
-
-
-
r
5alpha-pregnan-3,20-dione + NADPH + H+
5alpha-pregnane-3beta-ol-20-one + NADP+
show the reaction diagram
-
-
-
r
5alpha-pregnane-21-ol-3,20-dione + NADPH + H+
5alpha-pregnane-3beta,21-diol-20-one + NADP+
show the reaction diagram
-
-
-
r
5beta-androstan-3,17-dione + NADPH + H+
5beta-androstan-3beta-ol-17-one + NADP+
show the reaction diagram
-
-
-
r
5beta-androstan-3beta-ol-17-one + NADP+
5beta-androstan-3,17-dione + NADPH + H+
show the reaction diagram
-
-
-
r
5beta-androstane-3beta,17beta-diol + NADP+
5beta-androstane-17beta-ol-3-one + NADPH + H+
show the reaction diagram
-
-
-
r
5beta-cholanic acid-3,7-dione + NADPH + H+
5beta-cholanic acid-3beta-ol-7-one + NADP+
show the reaction diagram
-
-
-
r
5beta-dihydrocortisone + NADPH + H+
?
show the reaction diagram
-
-
-
-
r
5beta-dihydrocortisosterone + NADPH + H+
?
show the reaction diagram
-
-
-
-
r
5beta-dihydrotestosterone + NADPH + H+
3beta,17beta-dihydroxy-5beta-androstane + NADP+
show the reaction diagram
-
-
-
r
5beta-hydroxy-5beta cholanic acid + NADP+
3-oxo-5-beta-cholanic acid + NADPH + H+
show the reaction diagram
-
-
-
r
5beta-pregnan-3,20-dione + NADPH + H+
5beta-pregnane-3beta-ol-20-one + NADP+
show the reaction diagram
-
-
-
r
5beta-pregnane-20-ol-3-one + NADPH + H+
5beta-pregnane-3beta,20-diol + NADP+
show the reaction diagram
-
-
-
r
5beta-pregnane-21-ol-3,20-dione + NADPH + H+
5beta-pregnane-3beta,21-diol-20-one + NADP+
show the reaction diagram
-
-
-
r
5beta-pregnane-3beta,20alpha-diol + NADP+
5beta-pregnane-20alpha-ol-3-one + NADPH + H+
show the reaction diagram
-
-
-
r
5beta-pregnane-3beta,20beta-diol + NADP+
5beta-pregnane-20beta-ol-3-one + NADPH + H+
show the reaction diagram
-
-
-
r
5beta-pregnane-3beta,21-diol-20-one + NADP+
5beta-pregnane-21-ol-3,20-dione + NADPH + H+
show the reaction diagram
-
-
-
r
5beta-pregnane-3beta-ol-20-one + NADP+
5beta-pregnan-3,20-dione + NADPH + H+
show the reaction diagram
-
-
-
r
androstenedione + NAD(P)H
?
show the reaction diagram
-
-
-
-
?
avenastenone + NADPH
avenasterol + NADP+
show the reaction diagram
-
more than 72% compared with cholest-7-en-3-one, DELTA7-cholestenone
-
?
cholest-7-en-3-one + NADPH
3beta-hydroxy-cholest-7-ene + NADP+
show the reaction diagram
-
DELTA7-cholestenone, best substrate
DELTA7-cholesterol
ir
cholestanone + NADPH
cholestanol + NADP+
show the reaction diagram
-
57% compared with cholest-7-en-3-one, DELTA7-cholestenone
-
?
cycloartenone + NADPH
cycloartenol + NADP+
show the reaction diagram
-
7% compared with cholest-7-en-3-one, DELTA7-cholestenone
-
ir
cycloeucalenone + NADPH + H+
cycloeucalenol + NADP+
show the reaction diagram
-
putative endogenous substrate for sterone reductase
reverse oxidation: about 35% of forward reductase rate, 17-(4-isopropyl-1-methyl-pent-4-enyl)-4,13,14-trimethyl-tetradecahydro-cyclopropa[9,10]cyclopenta[a]phenanthren-3beta-ol
r
cycloeucalenone + NADPH + H+
cycloeucalenol + NADP+
show the reaction diagram
-
68% compared with cholest-7-en-3-one, DELTA7-cholestenone
reverse oxidation: about 35% of forward reductase rate, 17-(4-isopropyl-1-methyl-pent-4-enyl)-4,13,14-trimethyl-tetradecahydro-cyclopropa[9,10]cyclopenta[a]phenanthren-3beta-ol
r
cyclolaudenone + NADPH
cyclolaudenol + NADP+
show the reaction diagram
-
10% compared with cholest-7-en-3-one, DELTA7-cholestenone
-
?
dehydroepiandrosterone + NADH + H+
5-androstene-3,17-dione + NAD+
show the reaction diagram
-
-
-
?
dehydrolithocholic acid + NADPH + H+
?
show the reaction diagram
-
-
-
-
r
DELTA7-chondrillastenone + NADPH
DELTA7-chondrillasterol + NADP+
show the reaction diagram
-
70% compared with cholest-7-en-3-one, DELTA7-cholestenone, 5alpha,28beta(H)-stigmasta-7,22-dien-3-one
17-(4-ethyl-1,5-dimethyl-hex-2-enyl)-10,13-dimethyl-2,3,4,5,6,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3beta-ol
?
farnesol + NADP+
farnesal + NADPH + H+
show the reaction diagram
-
-
-
?
fecosterone + NADPH + H+
fecosterol + NADP+
show the reaction diagram
-
-
-
?
geranylgeraniol + NADP+
geranylgeranial + NADPH + H+
show the reaction diagram
-
-
-
?
isolithocholic acid + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
r
obtusifolione + NADPH
obtusifoliol + NADP+
show the reaction diagram
-
43% compared with cholest-7-en-3-one, DELTA7-cholestenone, 4,14-dimethyl-ergosta-8,24(28)-dien-3-one
4,14-dimethyl-ergosta-8,24(28)-dien-3-ol
?
obtusifolione + NADPH
obtusifoliol + NADP+
show the reaction diagram
-
4,14-dimethyl-ergosta-8,24(28)-dien-3-one
4,14-dimethyl-ergosta-8,24(28)-dien-3-ol
?
pregnenolone + NADH + H+
progesterone + NAD+
show the reaction diagram
-
-
-
?
progesterone + NADPH
pregn-4-ene-20alpha-ol-3-one + NADP+
show the reaction diagram
-
i.e. pregn-4-ene-3,20-dione
-
?
pyridine-3-aldehyde + NADP+
pyridin-3-ylmethanol + NADPH + H+
show the reaction diagram
-
-
-
?
spinastenone + NADPH
spinasterol + NADP+
show the reaction diagram
-
32% compared with cholest-7-en-3-one, DELTA7-cholestenone
-
?
zymosterone + NADPH
zymosterol + NADP+
show the reaction diagram
-
-
-
?
[7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one + NADPH
[7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-ol + NADP+
show the reaction diagram
-
i.e. tibolone, a synthetic hormone
-
-
[7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one + NADPH
[7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-ol + NADP+
show the reaction diagram
-
i.e. tibolone, a synthetic hormone
reaction product determination and analysis
-
methylglyoxal + NADP+
? + NADPH + H+
show the reaction diagram
-
-
-
?
additional information
?
-
-
substrate specificity
-
-
-
additional information
?
-
-
substrate specificity, coprostanol: not a substrate, 3-keto reducing enzyme is specific for a 5alpha, trans A/B ring junction in the sterone substrate, as found in all sterol biosynthesis intermediates
-
-
-
additional information
?
-
-
catalyzes the conversion of 3-keto-saturated steroids such as 5alpha-dihydrotestosterone, DHT, and 5alpha-androstane-3,17-dione, A-dione, into less active steroids
-
-
-
additional information
?
-
-
NADPH-dependent 3-ketosteroid reductase catalyzes reduction of the 3-keto group to a 3beta-hydroxyl group
-
-
-
additional information
?
-
-
4alpha-methyl-9beta,19-cyclo-C30-sterones and 4-desmethyl-DELTA7-C27-sterones or C30-sterones are preferentially reduced, 4,4-dimethyl-C30-sterones or C31-sterones react poorly. Produces stereoselectively corresponding 3beta-alcohol derivatives, no 3alpha-alcohol product is formed, catalyzes NADPH-dependent C-3 reduction of various sterones to produce stereoselectively the corresponding 3beta-hydroxy derivatives
-
-
-
additional information
?
-
-
sterol substrate specificity with 4alpha-monomethyl- and 4,4-dimethyl-3-ketosteroids, catalyzes NADPH-dependent reduction of 3-ketosteroid intermediates, 4-methyl sterol intermediates, of cholesterol biosynthesis from lanosterol, regenerates 3beta-hydroxy sterol
-
-
-
additional information
?
-
-
3-ketosteroid reductase activity of the human 3(alpha-beta)-hydroxysteroid epimerase catalyzes reduction of 3-ketosteroids to form 3beta-hydroxysteroids
-
-
-
additional information
?
-
-
enzyme of cholesterol biosynthesis
-
-
-
additional information
?
-
-
enzyme of sterol, ergosterol, biosynthesis, enzyme catalyzes last step in demethylation at C-4
-
-
-
additional information
?
-
-
enzyme of mevalonate pathway for biosynthesis of cholesterol from lanosterol
-
-
-
additional information
?
-
-
enzyme might form complexes with other proteins, including possibly DNA-binding proteins, under low ionic strength conditions
-
-
-
additional information
?
-
-
constitutive component of microsomal sterol 4-demethylation complex in photosynthetic organism
-
-
-
additional information
?
-
-
involved in the 10-step oxidative removal of the 4-gem-dimethyl group of sterols
-
-
-
additional information
?
-
-
step of biosynthesis of hormonal steroids
-
-
-
additional information
?
-
-
enzyme of plant sterol biosynthesis, involved in sterol-4 demethylation, invoves the removal of two methyl groups at C4
-
-
-
additional information
?
-
-
HSD17B7 participates in postsqualene cholesterol biosynthesis
-
-
-
additional information
?
-
-
HSD17B7 participates in postsqualene cholesterol biosynthesis, HSD17B7 is a novel candidate for inborn errors of cholesterol metabolism
-
-
-
additional information
?
-
-
the enzyme is also involved in synthesis of estradiol and estrone, neurosteroids paly a role in brain develkopment and in stimulation and control of song function
-
-
-
additional information
?
-
-
tibolone is used to treat climacteric symptoms and prevent osteoporosis, it exerts tissue-selective effects via site-specific metabolism into 3alpha- and 3beta-hydroxymetabolites and a DELTA4-isomer, In Hep-G2 cell cytosol and intact cells tibolone is exclusively reduced to 3beta-hydroxytibolone, tibolone metabolism in human liver is catalyzed by 3alpha/3beta-hydroxysteroid dehydrogenase activities of the four isoforms of the aldo-keto reductase (AKR)1C subfamily, overview
-
-
-
additional information
?
-
-
AKR1C1 is a cytosolic hydroxysteroid dehydrogenase, that reduces 3-ketosteroids and 20-ketosteroids, overview, molecular docking simulations with generation of docking targets, overview
-
-
-
additional information
?
-
-
comparison of substrate specificity and enantioselectivity of AKR1C isozymes, overview
-
-
-
additional information
?
-
-
the enzyme, termed AKR1B19, acts not only as a reductase for reactive carbonyl compounds derived from lipid peroxidation like AR-like proteins of other species, but also as a superior reductive 3beta-HSD for 3-keto-5alpha/beta-dihydro-C19/C21/C24-steroids
-
-
-
additional information
?
-
-
both isoforms of the enzyme catalyze the conversion of 3beta-hydroxy-5-ene-steroids (dehydroepiandrosterone, 17alpha-hydroxypregnenolone, pregnenolone) to 3-oxo-4-ene-steroids (androstenedione, 17alpha-hydroxyprogestrone, progesterone) on a single, dimeric protein containing both enzyme activities
-
-
-
additional information
?
-
-
substrate for 3-ketoreductase in the first sterol C-4 demethylation cycle is 4alpha-methylfecosterone, whereas that for the second C-4 demethylation cycle is fecosterone
-
-
-
additional information
?
-
-
substrate specificity of the bifunctional enzyme, for carbonyl compounds and steroids, overview. No reductase activity is observed for 17- and 20-ketosteroids, DELTA4-3-ketosteroids (testosterone, 4-androstene-3,17-dione and progesterone), and prostaglandins (D2, E2, and A1). In the reverse reaction, the enzyme oxidizes 3beta-hydroxy-5alpha/beta-dihydrosteroids, but shows no significant dehydrogenase activity for DELTA5-3beta-hydroxysteroids (dehydroepiandrosterone, pregnenolone, and 5-pregnene-3beta,20alpha-diol) and 3alpha-hydroxysteroids (5alpha/beta-androstan-3alpha-ol-17-ones, 5alpha/beta-androstane-3alpha,17beta-diols, 5alpha/beta-pregnan-3alpha-ol-20-ones and lithocholic acid). The reactivity towards all-trans-retinal of AKR1B19 is low
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(3)H-dehydroepiandrosterone + NAD(P)+
?
show the reaction diagram
-
-
-
-
?
2 17beta-hydroxy-5alpha-androstan-3-one + 2 NADPH + 2 H+
5alpha-androstane-3beta,17beta-diol + 5alpha-androstane-3alpha,17beta-diol + 2 NADP+
show the reaction diagram
Q04828
AKR1cs are a source of beta-tetrahydrosteroids. This is of physiological significance because the formation of 3beta-diol in contrast to 3alpha-diol is virtually irreversible, the 3beta-diol is a pro-apoptotic ligand for estrogen receptor beta, and 3beta-tetrahydrosteroids act as gamma-aminobutyric acid type A receptor antagonists
-
?
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
show the reaction diagram
-
in prostate cells AKR1C2 acts as a 3-ketosteroid reductase to eliminate 5alpha-dihydrotestosterone and prevents activation of androgen receptor. AKR1C2 does not act as an oxidase due to either potent product inhibition by NADPH or because it cannot surmount the oxidative 17beta-hydroxysteroid dehydrogenase present. AKR1C2 is not a source of 5alpha-dihydrotestosterone in PC-3 cells
-
?
androstenedione + NAD(P)H
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
catalyzes the conversion of 3-keto-saturated steroids such as 5alpha-dihydrotestosterone, DHT, and 5alpha-androstane-3,17-dione, A-dione, into less active steroids
-
-
-
additional information
?
-
-
catalyzes NADPH-dependent reduction of 3-ketosteroid intermediates, 4-methyl sterol intermediates, of cholesterol biosynthesis from lanosterol, regenerates 3beta-hydroxy sterol, enzyme of cholesterol biosynthesis
-
-
-
additional information
?
-
-
enzyme of cholesterol biosynthesis
-
-
-
additional information
?
-
-
enzyme of sterol, ergosterol, biosynthesis, enzyme catalyzes last step in demethylation at C-4
-
-
-
additional information
?
-
-
enzyme of mevalonate pathway for biosynthesis of cholesterol from lanosterol
-
-
-
additional information
?
-
-
enzyme might form complexes with other proteins, including possibly DNA-binding proteins, under low ionic strength conditions
-
-
-
additional information
?
-
-
constitutive component of microsomal sterol 4-demethylation complex in photosynthetic organism
-
-
-
additional information
?
-
-
involved in the 10-step oxidative removal of the 4-gem-dimethyl group of sterols
-
-
-
additional information
?
-
-
step of biosynthesis of hormonal steroids
-
-
-
additional information
?
-
-
enzyme of plant sterol biosynthesis, involved in sterol-4 demethylation, invoves the removal of two methyl groups at C4
-
-
-
additional information
?
-
-
HSD17B7 participates in postsqualene cholesterol biosynthesis
-
-
-
additional information
?
-
-
HSD17B7 participates in postsqualene cholesterol biosynthesis, HSD17B7 is a novel candidate for inborn errors of cholesterol metabolism
-
-
-
additional information
?
-
-
the enzyme is also involved in synthesis of estradiol and estrone, neurosteroids paly a role in brain develkopment and in stimulation and control of song function
-
-
-
additional information
?
-
-
tibolone is used to treat climacteric symptoms and prevent osteoporosis, it exerts tissue-selective effects via site-specific metabolism into 3alpha- and 3beta-hydroxymetabolites and a DELTA4-isomer, In Hep-G2 cell cytosol and intact cells tibolone is exclusively reduced to 3beta-hydroxytibolone, tibolone metabolism in human liver is catalyzed by 3alpha/3beta-hydroxysteroid dehydrogenase activities of the four isoforms of the aldo-keto reductase (AKR)1C subfamily, overview
-
-
-
additional information
?
-
-
the enzyme, termed AKR1B19, acts not only as a reductase for reactive carbonyl compounds derived from lipid peroxidation like AR-like proteins of other species, but also as a superior reductive 3beta-HSD for 3-keto-5alpha/beta-dihydro-C19/C21/C24-steroids
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
-
-
NADH
-
the NADH-linked reductase activity is only 18% of the NADPH-linked activity
NADH
-
-
NADP+
-
oxidation, poorly, only few substrates
NADP+
-
-
NADPH
-
specific for NADPH, NADH is essentially inactive, less than 10%
NADPH
-
specific for NADPH, NADH is essentially inactive, less than 10%
NADPH
-
NADPH-dependent
NADPH
-
NADPH preferred cofactor for 3-ketoreductase activity expressed type III isoform; specific for NADPH, NADH is essentially inactive, less than 10%
NADPH
-
AKR1B19 shows high coenzyme preference to NADPH
additional information
-
essentially inactive with NADH
-
additional information
-
essentially inactive with NADH
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
-
required
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(Z)-2-(4-methoxyphenylimino)-7-hydroxy-N-(pyridin-2-yl)-2H-chromene-3-carboxamide
-
noncompetitive in the reduction reaction, competitive in the oxidation reaction
-
3-(4-hydroxy-2-methoxyphenyl)acrylic acid 3-(3-hydroxyphenyl)propyl ester
-
uncompetitive in the reduction reaction, competitive in the oxidation reaction
-
5beta-cholanic acid-3alpha,7alpha-diol
-
-
acetonitrile
-
-
bisdemethoxycurcumin
-
-
diethylstilbestrol
-
-
dimethyl sulfoxide
-
-
Diphenic acid
-
competitive in the oxidation reaction
Epalrestat
-
-
ethanol
-
-
fenhexamid
-
Erg27 mutations causing amino acid substitutions in or near the transmembrane domain strongly decrease the affinity of fenhexamid for 3-ketoreductase. Sterol 3-ketoreductase sensitivity to fenhexamid in the various fungal strains, overview
Flufenamic acid
-
inhibits 3alpha-diol versus 3beta-diol formation
Flufenamic acid
-
in vitro and in vivo inhibition of AKR1C1
Ionic detergents
-
inactivation by strong solutions of ionic detergents, ethylene glycol minimizes inactivation
-
itraconazole
-
no inhibition
itraconazole
-
triazole antifungal agent, inhibits NADPH-dependent 3-ketosteroid reductase directly or indirectly
NADPH
-
the NAD+:NADPH ratio in cell will determinewhether AKR1C2 makes 5alpha-dihydrotestosterone
NADPH
-
potent inhibition of hydroxysteroid oxidase activity by low micromolar concentrations
oleanolic acid
-
competitive in the oxidation reaction
propan-2-ol
-
-
Tolrestat
-
competitive in the oxidation reaction
trilostane
-
IC50: 0.00023 mM
trilostane
-
competitive for 3beta-HSD1, noncompetitive for 3beta-HSD2
zopolrestat
-
-
minalrestat
-
competitive in the oxidation reaction
additional information
-
no inhibition by greatly increasing detergent concentration, Triton WR-1339, to a final concentration of 0.6%
-
additional information
-
no inhibition by azole inhibitors, 1 mM, pyrifenox, ketoconazole, and itraconazole, no inhibition by phenobarbital and pyrazole. No inhibition by 1 mM cyanide or 1 mM hydrogen peroxide, insensitive to carbon monooxide
-
additional information
-
NADPH-dependent 3-ketosteroid reductase activity is not inhibited by NAD+
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cytosolic Z protein
-
fatty acid-binding protein, membrane-bound enzyme, twofold to threefold activation, stimulatory activity is lost after solubilization of microsomal enzyme. Stimulation reversed by titration of Z-protein with either fatty acids or anti-Z-protein immunoglobulin. Stimulation not restored by incorporating partially purified reductase into an artificial phospholipid membrane
-
additional information
-
no activation by greatly increasing detergent concentration, Triton WR-1339, to a final concentration of 0.6%, no or poor activation by intestinal bile acid sequestrant, cholestyramine, no activation by bovine serum albumin
-
additional information
-
no effect, no activation by cholestyramine
-
additional information
-
no activation by 1 mM hydrogen peroxide
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0043
17beta-hydroxy-5alpha-androstan-3-one
-
pH 7.0, 37C, spectrophotometric analysis, formation of 3beta-androstanediol or 3alpha-androstanediol
0.085
24-methylenecycloartanone
-
-
0.162
24-methylenelophenone
-
-
0.078
4alpha-methyl-5alpha-cholest-7-en-3-one
-
solubilized enzyme
0.236
4alpha-methyl-5alpha-cholest-7-en-3-one
-
microsomal-bound enzyme
0.0035
5beta-dihydrotestosterone
-
pH 7.4, 25C, wild-type enzyme
0.0072
5beta-dihydrotestosterone
-
pH 7.4, 25C, mutant L116F
0.017
5beta-dihydrotestosterone
-
pH 7.4, 25C, mutant F303Q
0.02
5beta-dihydrotestosterone
-
pH 7.4, 25C, mutant M304S
0.039
5beta-dihydrotestosterone
-
pH 7.4, 25C, mutant F303Q/M304S
0.0023
5beta-pregnane-21-ol-3,20-dione
-
pH 7.4, 25C, mutant L116F
0.0024
5beta-pregnane-21-ol-3,20-dione
-
pH 7.4, 25C, wild-type enzyme
0.013
5beta-pregnane-21-ol-3,20-dione
-
pH 7.4, 25C, mutant F303Q
0.023
5beta-pregnane-21-ol-3,20-dione
-
pH 7.4, 25C, mutant M304S
0.05
5beta-pregnane-21-ol-3,20-dione
-
pH 7.4, 25C, mutant F303Q/M304S
0.22
cholestanone
-
-
0.067
cycloartenone
-
-
0.22
cycloeucalenone
-
-
0.1
cyclolaudenone
-
-
0.42
DELTA7-cholestenone
-
-
0.245
DELTA7-chondrillastenone
-
-
-
0.18
methylglyoxal
-
pH 7.4, 25C, mutant L116F
0.209
methylglyoxal
-
pH 7.4, 25C, mutant M304S
0.222
methylglyoxal
-
pH 7.4, 25C, wild-type enzyme
0.25
methylglyoxal
-
pH 7.4, 25C, mutant F303Q/M304S
0.253
methylglyoxal
-
pH 7.4, 25C, mutant F303Q
0.00012
NADPH
-
substrate: 5alpha-dihydrotestosterone, DHT
0.001
NADPH
-
pH 7.4, 25C, wild-type enzyme
0.003
NADPH
-
substrate: DELTA7-chondrillastenone
0.004
NADPH
-
substrate: cycloeucalenone
0.26
obtusifolione
-
-
0.011
Pyridine-3-aldehyde
-
pH 7.4, 25C, wild-type enzyme and mutant F303Q
0.022
Pyridine-3-aldehyde
-
pH 7.4, 25C, mutant L116F
0.039
Pyridine-3-aldehyde
-
pH 7.4, 25C, mutant M304S
0.048
Pyridine-3-aldehyde
-
pH 7.4, 25C, mutant F303Q/M304S
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.003
17beta-hydroxy-5alpha-androstan-3-one
Homo sapiens
-
pH 7.0, 37C, radiometric analysis, formation of 3beta-androstanediol
0.0493
17beta-hydroxy-5alpha-androstan-3-one
Homo sapiens
-
pH 7.0, 37C, radiometric analysis, formation of 3alpha-androstanediol
0.052
17beta-hydroxy-5alpha-androstan-3-one
Homo sapiens
-
pH 7.0, 37C, spectrophotometric analysis, formation of 3beta-androstanediol or 3alpha-androstanediol
0.02
5beta-dihydrotestosterone
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant F303Q/M304S
0.047
5beta-dihydrotestosterone
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant M304S
0.08
5beta-dihydrotestosterone
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant F303Q
0.107
5beta-dihydrotestosterone
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant L116F
0.113
5beta-dihydrotestosterone
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.023
5beta-pregnane-21-ol-3,20-dione
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant F303Q/M304S
0.042
5beta-pregnane-21-ol-3,20-dione
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant M304S
0.062
5beta-pregnane-21-ol-3,20-dione
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant F303Q
0.063
5beta-pregnane-21-ol-3,20-dione
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant L116F
0.092
5beta-pregnane-21-ol-3,20-dione
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.3
methylglyoxal
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.32
methylglyoxal
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant L116F
0.37
methylglyoxal
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant M304S
0.4
methylglyoxal
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant F303Q/M304S
0.58
methylglyoxal
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant F303Q
0.73
NADPH
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.6
Pyridine-3-aldehyde
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant L116F
0.72
Pyridine-3-aldehyde
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.78
Pyridine-3-aldehyde
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant M304S
0.87
Pyridine-3-aldehyde
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant F303Q
1.2
Pyridine-3-aldehyde
Oryctolagus cuniculus
-
pH 7.4, 25C, mutant F303Q/M304S
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0001
trilostane
-
3beta-HSD1 wild-type, pH 7.4, 27C
0.00019
trilostane
-
3beta-HSD2 mutant P195R, pH 7.4, 27C
0.0016
trilostane
-
3beta-HSD2 wild-type, pH 7.4, 27C
0.00256
trilostane
-
3beta-HSD1 mutant R195P, pH 7.4, 27C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000008
(Z)-2-(4-methoxyphenylimino)-7-hydroxy-N-(pyridin-2-yl)-2H-chromene-3-carboxamide
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
-
0.00006
3-(4-hydroxy-2-methoxyphenyl)acrylic acid 3-(3-hydroxyphenyl)propyl ester
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
-
0.0017
AL1567
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.0006
bisdemethoxycurcumin
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.0028
diethylstilbestrol
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.26
Diphenic acid
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.0015
Epalrestat
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.000043
minalrestat
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.0004
oleanolic acid
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.0015
quercetin
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.0053
Sorbinil
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.00086
sulindac
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.00016
Tolrestat
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
0.00023
trilostane
Rattus norvegicus
-
IC50: 0.00023 mM
0.0012
zopolrestat
Oryctolagus cuniculus
-
pH 7.4, 25C, wild-type enzyme
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0014
-
partially purified enzyme
0.0039
-
with substrate 5alpha-dihydrotestosterone, formation of the 3alpha-hydroxysteroid
0.0161
-
with substrate 5alpha-dihydrotestosterone, formation of the 3beta-hydroxysteroid
0.0312
-
with substrate tibolone
0.0432
-
with substrate progesterone
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7
-
assay at
7.4
-
assay at
7.4
-
assay at
7.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
assay at
27
-
assay at
30
-
assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
adult, juvenile, and developing
Manually annotated by BRENDA team
-
selective expression of 3beta-HSD1
Manually annotated by BRENDA team
-
high expression levels in the ganglion of the trigeminal nerve and the dorsal root ganglia
Manually annotated by BRENDA team
-
of the trigeminal nerve, dorsal root ganglia, cranial ganglia
Manually annotated by BRENDA team
-
HepG2 cells which lack 3-ketohydroxysteroid reductase/DELTA5-4ketosteroid isomerase mRNA expression, but express AKR1C1-AKR1C3 are able to convert 17beta-hydroxy-5alpha-androstan-3-one to 3beta-androstanediol and 3alpha-androstanediol
Manually annotated by BRENDA team
-
primary, time-dependent reduction of tibolone into 3beta- and 3alpha-hydroxytibolone was observed again in a 4:1 ratio
Manually annotated by BRENDA team
-
AKR1C2 is not a source of 5alpha-dihydrotestosterone in PC-3 cells
Manually annotated by BRENDA team
-
selective expression of 3beta-HSD1
Manually annotated by BRENDA team
-
in primary cultures of epithelial cells, high levels of AKR1C2 transcripts are detected in prostate cancer, but not in cell from normal prostate. In prostate cells AKR1C2 acts as a 3-ketosteroid reductase to eliminate 5alpha-dihydrotestosterone and prevents activation of androgen receptor
Manually annotated by BRENDA team
-
in primary cultures of epithelial cells, high levels of AKR1C2 transcripts are detected in prostate cancer, but not in cell from normal prostate
Manually annotated by BRENDA team
-
selective expression of 3beta-HSD1
Manually annotated by BRENDA team
additional information
-
specifically expressed in tissues that are involved in the pathogenesis of congenital cholesterol-deficiency disorders
Manually annotated by BRENDA team
additional information
-
no differences in activity and localization between femal and male animals, except for the juvenile female slices which shows increased activity
Manually annotated by BRENDA team
additional information
-
the enzyme expression occurs in all rabbit tissues, although its expression levels in the renal cortex, adrenal gland, small intestine and colon are high
Manually annotated by BRENDA team
additional information
-
isozymes 3beta-HSD1 and 3beta-HSD2 are encoded by two distinct genes which are expressed in a tissue-specific pattern
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
microsomal-bound
-
Manually annotated by BRENDA team
additional information
-
-
-
Manually annotated by BRENDA team
additional information
-
3-keto reductase activity in both microsomal fractions and intact cells
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
35000
-
native enzyme, gel filtration
724124
additional information
-
chromatography on Sepharose 2B column shows ketoreductase activity eluted as high-molecular-weight complex
286472
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
2 h at 25C: 84% of activity remained, 8 h at 25C: 74-76% of activity remained
286475
additional information
-
-
286475
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
enzyme extreme labile
-
enzyme stable in presence of high concentrations of detergents
-
ethylene glycol stabilizes
-
stable against subtilisin VII, no attendent loss of 3-ketoreductase activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant wild-type and mutant enzymes from Sf9 insect cells by ultracentrifugation
-
native enzyme from lungs by ammonium sufate fractionation, gel filtration, and anion exchange chromatography, recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21 (DE3) pLysS by nickel affinity chromatography and ultrafiltration
-
solubilization with Lubrol-WX in the presence of cholic acid, and partial purification
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
3-ketosteroid reductase activity of the human 3(alpha-beta)-hydroxysteroid epimerase, stable expression
-
expression of HSD17B7 and truncated HSD17B7 (shortened by 127 amino acids at the C terminus) as glutathione-S-transferase fusion protein in Escherichia coli. Erg27p-deficient yeast strain complements the 3-ketosteroid reductase deficiency of the cells and restores growth on sterol-deficient medium
-
expression of wild-type and mutant enzymes in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system
-
overexpression in Escherichia coli
-
quantitative expression analysis of AKR1C isozymes
-
expression of HSD17B7 as a glutathione-S-transferase fusion protein in Escherichia coli. Erg27p-deficient yeast strain complements the 3-ketosteroid reductase deficiency of the cells and restores growth on sterol-deficient medium
-
DNA and amino acid sequence determination and analysis, expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21 (DE3) pLysS
-
isoform type III of 3beta-hydroxysteroid dehydrogenase/DELTA5-DELTA4 isomerase with almost exclusive 3-ketosteroid reductase activity, cDNA expression
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D61N
-
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
D61V
-
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
DELTA214-341
-
inactive mutant enzyme
P195R
-
site-directed mutagenesis, mutation in isozyme 3beta-HSD2
R195P
-
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
F303Q
-
site-directed mutagenesis, the enzyme shows reduced 3-ketoreductase activity compared to the wild-type enzyme
F303Q/M304S
-
site-directed mutagenesis, the enzyme shows reduced 3-ketoreductase activity compared to the wild-type enzyme. The double mutation impairs the affinity and catalytic efficiency, although it did not affect the stereospecific reduction of the two 3-ketosteroids into the corresponding 3beta-hydroxysteroids
L116F
-
site-directed mutagenesis
M304S
-
site-directed mutagenesis, the enzyme shows reduced 3-ketoreductase activity compared to the wild-type enzyme. The M304S mutation causes a 4fold increase in the Km value for pyridine-3-aldehyde
additional information
-
erg27 mutation and erg27 polymorphism in different strains and fenhexamid phenotypes, overview
E192A
-
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
additional information
overexpression of 17beta-hydroxysteroid dehydrogenase type 7 in ERG27-deleted yeast cells. Recombinant strains grow more slowly than the control yeast ERG27-overexpressing strain on sterol-deficient media, whereas the growth rate is normal on media supplemented with a 3-ketoreductase substrate. Mammalian steroid-3-ketoreductase expressed in yeast shows full enzymatic functioanlity but is unable to support the functionality of yeast oxidosqualene cyclase as ERG27 does
T8A
-
site-directed mutagenesis, mutation in isozyme 3beta-HSD1
additional information
overexpression of 17beta-hydroxysteroid dehydrogenase type 7 in ERG27-deleted yeast cells. Recombinant strains grow more slowly than the control yeast ERG27-overexpressing strain on sterol-deficient media, whereas the growth rate is normal on media supplemented with a 3-ketoreductase substrate. Mammalian steroid-3-ketoreductase expressed in yeast shows full enzymatic functioanlity but is unable to support the functionality of yeast oxidosqualene cyclase as ERG27 does
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
the selective inhibition of human 3beta-HSD1 in breast tumors represents a potential treatment for hormone-sensitive breast cancer
analysis
-
enzyme can be used for reconstitution of 4-methyl sterol demethylations of cholesterol biosynthesis from lanosterol