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Information on EC 1.1.1.213 - 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific)
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EC Tree
1.1.1.213 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific)IUBMB Comments
The enzyme acts on multiple 3alpha-hydroxysteroids. Re-specific with respect to NAD+ or NADP+ [cf. EC 1.1.1.50, 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific)]. Enzymes whose stereo-specificity with respect to NAD+ or NADP+ is not known are described by EC 1.1.1.357, 3alpha-hydroxysteroid 3-dehydrogenase.
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Word Map
- 1.1.1.213
- androgen
-
aldo-keto
-
5alpha-reductase
-
polycyclic
-
alpha-hydroxysteroids
-
17beta-hydroxysteroid
- 5alpha-dihydrotestosterone
- akr1c2
-
neurosteroids
- dihydrotestosterone
-
trans-dihydrodiols
- 17beta-hsd
- androsterone
-
hydroxysteroids
-
gabaa
- allopregnanolone
-
20alpha-hydroxysteroid
- 20alpha-hsds
-
3alpha-diol
-
5alpha-dht
-
i-babp
- 3alpha-androstanediol
- 5alpha-androstane-3alpha,17beta-diol
-
5alpha-reduced
- o-quinones
- testosteroni
-
1.1.1.50
-
17beta
-
neurosteroidogenic
- 5alpha-dihydroprogesterone
-
alicyclic
-
3alpha,5alpha-thp
-
5alpha-reduction
- diagnostics
- drug development
- medicine
- synthesis
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
17beta-HSD type 5, 17beta-hydroxysteroid dehydrogenase type 5, 3-alpha hydroxysteroid oxidoreductase, 3-alpha-HSO, 3alpha-HSD, 3alpha-HSD type 2, 3alpha-HSD type 3, 3alpha-HSD/CR, 3alpha-HSD3, 3alpha-HSOR, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3alpha-HSD
3alpha-hydroxysteroid dehydrogenase
3alpha-hydroxysteroid dehydrogenase (B-specific)
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-
-
-
3alpha-hydroxysteroid oxidoreductase
-
-
-
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3alpha-hydroxysteroid:NAD(P) oxidoreductase
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-
-
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3alphaHSD
A-specific 3alpha-hydroxysteroid dehydrogenase
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-
-
-
AKR1C2
AKR1C3
AKR1C9
B-specific 3alpha-hydroxysteroid dehydrogenase
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-
-
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type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase
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-
additional information
3alpha-hydroxysteroid dehydrogenase
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-
-
-
additional information
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cf. EC 1.1.1.50, the enzyme belongs to the short chain dehydrogenase/reductase protein superfamily
additional information
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the enzyme belongs to the short-chain dehydrogenase/reductase family
additional information
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cf. EC 1.1.1.239, the enzyme belongs to the AKR1C subfamily
additional information
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cf. EC 1.1.1.50, the enzyme belongs to the aldo-keto reductase subfamily AKR1C
additional information
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cf. EC 1.1.1.50, the enzyme belongs to the aldo-keto reductase, AKR, superfamily
additional information
the enzyme is a member of the aldo-keto reductase family
additional information
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cf. EC 1.1.1.50, the enzyme belongs to the AKR1C family
additional information
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cf. EC 1.1.1.50, the enzyme belongs to the AKR1C family
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additional information
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cf. EC 1.1.1.50, the enzyme belongs to the short-chain dehydrogenase/reductase family
additional information
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cf. EC 1.1.1.50, the enzyme is a member of the aldo-keto reductase superfamily
additional information
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see also EC 1.1.1.50, 3alpha-hydroxysteroid dehydrogenase (B-specific), for enzymes catalyzing the same reaction, but which are B-specific with respect to hydrogen transfer to/from NAD(P)+/NAD(P)H. Enzymes without information of stereospecificity are summarized under EC 1.1.1.50, but may in fact belong to EC 1.1.1.213
additional information
the enzyme belongs to the aldo-keto reductase gene family
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
bi bi mechanism, NADP+ binds to the free enzyme before the hydroxysteroid substrate, the ketosteroid product leaves first, followed by NADPH
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
bi bi mechanism, pyridine nucleotide binds first and leaves last; binding and release or pyridine is rate-limiting
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
bi bi mechanism, pyridine nucleotide binds before substrate
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
ordered and sequential mechanism, nucleotide binds first and leaves last
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
short-chain alcohol/polyol dehydrogenase family
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
aldoketoreductase superfamily; bi bi mechanism, pyridine nucleotide binds before substrate
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
aldoketoreductase superfamily; bi bi mechanism, pyridine nucleotide binds first and leaves last
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
aldoketoreductase superfamily; bi bi mechanism, pyridine nucleotide binds first and leaves last; ordered and sequential mechanism, nucleotide binds first and leaves last
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
ordered bi bi reaction mechanism
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
catalytic triad residues Ser114, Tyr155, and Lys159 have mechanistic roles in the catalytic reaction
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
the reduction reaction is slightly preferred by the wild-type enzyme, which is determined by residue Arg276
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
the enzyme reveals an 'induced-fit' mechanism involving a bound citrate ion and a conserved basic motif involved in the binding of androgen, the enzyme also binds many structurally different molecules such as 4-hydroxynonenal, polycyclic aromatic hydrocarbons, and indanone, modeling of substrate binding
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
the enzyme shows a sequential ordered reaction mechanism, where NAD+ binds to the enzyme first and NADH leaves last
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
bi bi ordered mechanism, kinetic analysis, overview
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
The overall oxidoreductive reaction comprises the deprotonation of tyrosine, proton abstraction by the tyrosinate anion, and hydride transfer from the hydroxysteroid to NAD+, followed by the release of a proton from the hydroxy group of tyrosine to the solution., The proton transfer to the external base, from Tyr155 to Lys159 via 2'-OH of ribose, with a late transition state is the rate-limiting step, mechanism, overview
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
short-chain alcohol/polyol dehydrogenase family
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
bi bi mechanism, pyridine nucleotide binds before substrate; ordered and sequential mechanism, nucleotide binds first and leaves last
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a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
redox reaction
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-
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reduction
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oxidation
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-
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
3alpha-hydroxysteroid:NAD(P)+ 3-oxidoreductase (Re-specific)
The enzyme acts on multiple 3alpha-hydroxysteroids. Re-specific with respect to NAD+ or NADP+ [cf. EC 1.1.1.50, 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific)]. Enzymes whose stereo-specificity with respect to NAD+ or NADP+ is not known are described by EC 1.1.1.357, 3alpha-hydroxysteroid 3-dehydrogenase.
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CAS REGISTRY NUMBER
COMMENTARY
9028-56-2
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(11S,12S)-11,12-dihydrobenzo[g]chrysene-11,12-diol + NADP+
? + NADPH + H+
-
enzyme is stereoselective for benzo[g]chrysene-11S,12S-dihydrodiol
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
the rate of dihydrotestosterone reduction over back-conversion is 2.4 and 5.9 for prostate and epididymis, respectively
-
r
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
17beta-hydroxy-5alpha-androstan-3-one + NADPH
3alpha,17beta-dihydroxy-5alpha-androstan + NADP+
-
-
-
r
2-acetylpyridine + NADPH
1-(2-pyridyl)ethanol + NADP+
-
stereoselective catalysis producing mainly the (S)-alcohols
-
-
?
3-acetylpyridine + NADPH
1-(3-pyridyl)ethanol + NADP+
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low activity, stereoselective catalysis producing mainly the (S)-alcohols
-
-
?
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH + H+
-
steroid reduction direction is preferred
-
-
r
4'-methoxyacetophenone + NADPH + H+
1-(4-methoxyphenyl)ethanol + NADP+
-
-
R,S-enantiomeric product
-
?
4-acetylpyridine + NADPH
1-(4-pyridyl)ethanol + NADP+
-
stereoselective catalysis producing mainly the (S)-alcohols
-
-
?
4-androsten-3alpha-ol-17-one + NADH + H+
4-androsten-3alpha,17beta-diol + NAD+
-
AKR1C17
-
-
r
4-androstene-3,17-dione + NADH + H+
4-androsten-3alpha-ol-17-one + NAD+
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low activity
-
-
r
4-bromoacetophenone + NADPH + H+
1-(4-bromophenyl)ethanol + NADP+
-
-
-
-
?
4-cyanoacetophenone + NADPH + H+
1-(4-cyanophenyl)ethanol + NADP+
-
-
-
-
?
4-methylacetophenone + NADPH + H+
1-(4-methylphenyl)ethanol + NADP+
-
-
R,S-enantiomeric product
-
?
4-nitroacetophenone + NAD(P)H
1-(4-nitrophenyl)ethanol + NAD(P)+
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pH 6.0
-
?
4-nitroacetophenone + NADPH + H+
1-(4-nitrophenyl)ethanol + NADP+
-
-
-
-
?
5alpha-androstan-17beta-ol-3-one + NADPH + H+
5alpha-androstan-3alpha,17beta-diol + NADP+
-
-
-
?
5alpha-androstane-3,17-dione + NADH
5alpha-androstan-3alpha-ol-17-one + NAD+
-
low activity
AKR1C9
-
r
5alpha-androstane-3alpha,17beta-diol + NADP+
5alpha-androstane-17beta-ol-3-one + NADPH
-
-
-
r
5alpha-androstanedione + NADPH + H+
5alpha-androstan-3alpha-ol-17-one + NADP+
-
-
i.e. allopregnanolone
-
?
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnan-3alpha-ol-20-one + NAD(P)+
-
regulation of the amount of allosteric agonists that can bind to the GABA receptor in brain
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r
5alpha-pregnan-3alpha,21-diol-20-one + NADP+
5alpha-pregnan-21-ol-3,20-dione + NADPH
-
-
-
r
5alpha-pregnane-20alpha-ol-3-one + NADH
5alpha-pregnane-3,20alpha-diol + NAD+
-
-
-
-
?
5alpha-pregnane-3,20-dione + NADH
5alpha-pregnan-3alpha-ol-20-one + NAD+
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low activity
-
-
r
5beta-androstan-3alpha-ol-17-one + NAD(P)+
5beta-androstane-3,17-dione + NAD(P)H
-
-
-
-
r
5beta-androstan-3alpha-ol-17-one + NADH
5beta-androstane-3alpha,17beta-diol + NAD+
-
-
-
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r
5beta-androstan-3alpha-ol-17-one + NADP+
5beta-androstan-3,17-dione + NADPH
-
-
-
?
5beta-androstane-3,17-dione + NADH
5beta-androstan-3alpha-ol-17-one + NAD+
-
-
-
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r
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstane-17beta-ol-3-one + NADPH
-
-
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r
5beta-dihydrocortisone + NADPH
3alpha,17alpha,21-trihydroxy-5beta-pregnan-11,20-dione + NADP+
-
-
-
?
5beta-pregnan-3alpha-ol-20-one + NAD(P)+
5beta-pregnane-3,20-dione + NAD(P)H
-
-
-
-
r
5beta-pregnan-3alpha-ol-20-one + NADP+
5beta-pregnane-3,20-dione + NADPH
-
-
-
r
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione + NAD(P)H
5beta-pregnane-3alpha,17alpha,20beta,21-tetraol-11-one + NAD(P)+
5beta-pregnane-20alpha-ol-3-one + NADH + H+
5beta-pregnane-3,20alpha-diol + NAD+
-
-
-
-
?
5beta-pregnane-3,20-dione + NADH + H+
5beta-pregnan-3alpha-ol-20-one + NAD+
-
-
-
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r
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one + NADH
?
-
the enzyme produces both R- and S-form products in a ratio of 2.3 : 1
-
-
?
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NADPH + H+
5beta-cholestane-3alpha,7alpha,12alpha-triol + NADP+
-
-
-
-
?
7alpha-hydroxy-5beta-cholestan-3-one + NADPH + H+
5beta-cholestane-3alpha,7alpha-diol + NADP+
-
-
-
-
?
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADPH
9-[hydroxy(phenyl)methyl]-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADP+
androstan-17beta-ol-3-one + NADH
androstan-3alpha,17beta-diol + NAD+
-
-
-
?
androstan-3,17-dione + NADH
androstan-3alpha-ol-17-one + NAD+
-
-
-
?
androsterone + NAD+
5alpha-androstane-3,17-dione + NADH
-
-
-
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r
benzo[c]phenanthrene-3,4-dihydrodiol + NADP+
? + NADPH + H+
-
enzyme metabolizes both stereoisomers of benzo[c]phenanthrene-3,4-dihydrodiol
-
-
?
etiocholane-3,17-dione + NADH
etiocholan-3alpha-ol-17-one + NAD+
-
-
-
?
glycochenodeoxycholic acid + NADP+
7alpha-hydroxy-3-oxo-5beta-cholanoyl glycine + NADPH
-
-
-
?
glycolithocholic acid + NADP+
3-oxo-5beta-cholanoyl glycine + NADPH
-
-
-
?
pregnane-11beta,17alpha,21-triol-3,20-dione + NADH
pregnane-3alpha,11beta,17alpha,21-tetrol-20-one + NAD+
-
-
-
?
progesterone + NAD(P)H
3alpha-hydroxy-pregn-4-ene-20-one + NAD(P)+
-
-
-
-
r
prostaglandin + NADP+
? + NADPH
-
types A1, A2, B1, B2, D2, E1, E2, F1, F2alpha and 15-keto-prostaglandinE2 and F2alpha
-
-
prostaglandin-F2alpha + NADP+
prostaglandin F2 + prostaglandin B2 + NADPH
-
-
-
?
testosterone + NAD(P)H + H+
4-androsten-3alpha,17beta-diol + NAD(P)+
-
-
-
-
r
1-(4'nitrophenyl)prop-2-en-1-ol + NAD+
1-(4'nitrophenyl)prop-2-en-1-one + NADH
-
-
-
?
1-(4'nitrophenyl)prop-2-en-1-ol + NAD+
1-(4'nitrophenyl)prop-2-en-1-one + NADH
-
-
-
?
1-(4'nitrophenyl)prop-2-yn-1-ol + NAD+
1-(4'nitrophenyl)prop-2-yn-1-one + NADH
-
-
-
?
1-(4'nitrophenyl)prop-2-yn-1-ol + NAD+
1-(4'nitrophenyl)prop-2-yn-1-one + NADH
-
-
-
?
1-acenaphthenol + NAD(P)+
1-acenaphthenone + NAD(P)+
-
pH 9.0
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
termination of androgen action
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
conversion in animal tissues
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
regulation of the amount of androgen in prostate, high levels of substrate are required for normal and abnormal growth of prostate
-
r
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
termination of androgen action
-
?
2 tibolone + 2 NADPH + 2 H+
3alpha-hydroxytibolone + 3beta-hydroxytibolone + 2 NADP+
-
i.e. tibolone, a 3-ketosteroid androgen receptor, conversion to potent estrogen receptor alpha agonists, tibolone induces estrogen receptor alpha-dependent gene promoter activity through cis-acting estrogen response elements, increases the stimulatory effect of TGF-beta on Smad-dependent gene promoter activity, and enhances prostaglandin E2-induced activity of transcription factor Runx2, overview
3alpha-hydroxytibolone is the primary metabolite
-
r
2 tibolone + 2 NADPH + 2 H+
3alpha-hydroxytibolone + 3beta-hydroxytibolone + 2 NADP+
-
i.e. tibolone, a 3-ketosteroid androgen receptor, conversion to potent estrogen receptor alpha agonists, overview
3alpha-hydroxytibolone is the primary metabolite
-
r
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
-
i.e. 3alpha,5alpha-tetrahydroprogesterone or 3alpha,5alpha-THP, the enzyme catalyzes the biosynthesis and oxidation of 3alpha,5alpha-reduced neurosteroids as allopregnanolone, which stimulates GABAA receptors, sciatic nerves-induced analgesia results in increased enzyme levels in neuropathic rats, overview
-
-
r
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
-
i.e. 3alpha,5alpha-tetrahydroprogesterone or 3alpha,5alpha-THP
-
-
r
3alpha-hydroxy-5alpha-androstan-17-one + NAD+
5alpha-androstan-3,17-dione + NADH
-
-
-
r
3alpha-hydroxy-5alpha-androstan-17-one + NAD+
5alpha-androstan-3,17-dione + NADH
-
-
-
r
3alpha-hydroxy-5alpha-androstan-17-one + NAD+
5alpha-androstan-3,17-dione + NADH
-
-
-
r
3alpha-hydroxy-5alpha-androstan-17-one + NAD+
5alpha-androstan-3,17-dione + NADH
-
pH 9.0
-
-
3alpha-hydroxy-5alpha-androstan-17-one + NAD+
5alpha-androstan-3,17-dione + NADH
-
pH 9.0
-
-
3alpha-hydroxy-5alpha-androstan-17-one + NADP+
5alpha-androstan-3,17-dione + NADPH
-
-
-
r
3alpha-hydroxy-5alpha-androstan-17-one + NADP+
5alpha-androstan-3,17-dione + NADPH
-
-
-
r
4-nitrobenzaldehyde + NAD(P)H
(4-nitrophenyl)methanol + NAD(P)+
-
pH 6.0
-
-
4-nitrobenzaldehyde + NAD(P)H
(4-nitrophenyl)methanol + NAD(P)+
-
pH 6.0
-
?
4-nitrobenzaldehyde + NAD(P)H
(4-nitrophenyl)methanol + NAD(P)+
-
NADH as cofactor
-
-
5alpha-androstan-3,17-dione + NAD(P)H
3alpha-hydroxy-5alpha-androstan-17-one + NAD(P)+
-
-
r
5alpha-androstan-3,17-dione + NAD(P)H
3alpha-hydroxy-5alpha-androstan-17-one + NAD(P)+
-
pH 6.0 for reduction, pH 7.0 and 9.0 for androsterone oxidation
-
r
5alpha-androstan-3,17-dione + NAD(P)H
3alpha-hydroxy-5alpha-androstan-17-one + NAD(P)+
-
pH 6.0 for reduction, pH 7.0 and 9.0 for androsterone oxidation
-
r
5alpha-androstan-3alpha-ol-17-one + NADH + H+
5beta-androstan-3alpha,17beta-diol + NAD+
-
-
-
-
-
5alpha-androstan-3alpha-ol-17-one + NADH + H+
5beta-androstan-3alpha,17beta-diol + NAD+
-
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
-
-
-
?
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
-
-
-
?
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
-
inactivation of the potent androgen in human prostate
-
-
r
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
-
inactivation of the potent androgen in human prostate, fluorometric activity measurement in intact cells, overview
-
-
?
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
-
i.e. DHT
-
-
?
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
-
i.e. DHT
-
-
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
androgen-inactivating enzyme
-
-
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
the enzyme is important in inactivation of DHT
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
the enzyme plays a crucial role in the regulation of the intracellular concentrations of testosterone and 5alpha-dihydrotestosterone, two steroids directly linked to the etiology and the progression of many prostate diseases and cancer, overview
-
-
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
i.e. DHT
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
i.e. DHT, substrate and cofactor binding site structure
-
-
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
i.e. DHT, the enzyme prefers the reductive reaction
-
-
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
i.e. DHT
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
-
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
i.e. DHT or 5alpha-androstane-17beta-ol-3-one, the reduction reaction is slightly preferred by the wild-type enzyme, which is determined by residue Arg276
i.e. 5alpha-androstane-3alpha,17beta-diol
-
?
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
-
steroid reduction direction is preferred
-
-
r
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
-
the chemical oxidation step is rate-limiting, W227 is very important for cataylsis, steroid reduction direction is preferred
-
-
r
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione + NAD(P)H
5beta-pregnane-3alpha,17alpha,20beta,21-tetraol-11-one + NAD(P)+
-
-
-
r
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione + NAD(P)H
5beta-pregnane-3alpha,17alpha,20beta,21-tetraol-11-one + NAD(P)+
-
hepatic reduction in animal tissues
-
?
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADPH
9-[hydroxy(phenyl)methyl]-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADP+
-
competitive substrate, fluorometric activity measurement in intact cells, overview
-
-
?
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADPH
9-[hydroxy(phenyl)methyl]-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADP+
-
competitive substrate
-
-
?
androsterone + NAD+
androstanedione + NADH
-
the intramolecular proton transfer is a rate-limiting step, with a concomitant releasing of protons to bulk solvent
-
-
r
benzenedihydrodiol + NAD(P)+
? + NAD(P)+
-
pH 9.0
-
?
cholic acid + NAD(P)+
3-oxocholate + NAD(P)H
-
-
very little activity
?
cholic acid + NAD(P)+
3-oxocholate + NAD(P)H
-
-
very little activity
?
choloyl-CoA + NAD(P)+
3-oxocholoyl-CoA + NAD(P)H + H+
-
-
-
r
deoxycholoyl-CoA + NAD(P)+
3-oxodeoxycholoyl-CoA + NAD(P)H + H+
-
75% activity compared with cholyl-CoA
-
?
deoxycholoyl-CoA + NAD(P)+
3-oxodeoxycholoyl-CoA + NAD(P)H + H+
-
75% activity compared with cholyl-CoA
-
?
tibolone + NADPH
3-hydroxytibolone + NADP+
-
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
-
-
?
tibolone + NADPH
3-hydroxytibolone + NADP+
-
i.e. [7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, stereoselctive reaction to the 3alpha-hydroxytibolone product
-
-
?
additional information
?
-
-
bifunctional enzyme exhibiting 3alpha-hydroxysteroid dehydrogenase activity and carbonyl reductase activity
-
-
-
additional information
?
-
-
no activity with cholate, chenodeoxycholate, deoxycholate, glycocholate, taurocholate, ursodeoxycholate and bile acid
-
-
-
additional information
?
-
-
no activity with cholate, chenodeoxycholate, deoxycholate, glycocholate, taurocholate, ursodeoxycholate and bile acid
-
-
-
additional information
?
-
the enzyme is important in the synthesis of neuroactive 5alpha/beta-pregnan-3alpha-ol-20-ones from their precursors, the enzyme plays a role in development and progression of prostate cancer
-
-
-
additional information
?
-
the RODH like 3alpha/17beta-HSD, EC 1.1.1.239, regulates the transactivation of AKR1C2, overview
-
-
-
additional information
?
-
-
besides 3alpha-hydroxysteroid dehydrogenase activity, the enzyme shows also 17beta-hydroxysteroid dehydrogenase activity towards 5alpha-dihydrotestosterone, EC 1.1.1.239, overview, the enzyme reveals an 'induced-fit' mechanism and a conserved basic motif involved in the binding of androgen, the enzyme also binds many structurally different molecules such as 4-hydroxynonenal, polycyclic aromatic hydrocarbons, and indanone
-
-
-
additional information
?
-
-
AKR1C3 catalyzes androgen, estrogen, and prostaglandin metabolism, AKR1C3 is also involved in cancer development or progression
-
-
-
additional information
?
-
-
an androgen-inactivating enzyme, important in androgen and progesterone metabolism
-
-
-
additional information
?
-
-
the enzyme might play an important role in female physiology, substrate specificity, overview
-
-
-
additional information
?
-
-
metabolizes androgens and glucocorticoids, function as a dihydrodiol dehydrogenase as well as 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase, enzyme catalyzes both oxidation and reduction reaction at physiological pH and is able to reduce aromatic ketones
-
-
-
additional information
?
-
-
the enzyme displays a distinct preference for the reduction of quinones, e.g. 9,10-phenanthrenequinone, and 3-oxo steroids, e.g. androstane, pregnane and cholane, over aromatic aldehydes and ketones, whereas 3alpha-hydroxy steroids are overwhelmingly more efficiently oxidized than are 1-acenaphthenol or benzenedihydrodiol. Ethanol and 3beta-hydroxy steroids no substrates
-
-
-
additional information
?
-
-
oxidation of 3alpha-hydroxysteroids, secondary alcohols and trans-dihydrodiol proximate carcinogens derived from polycyclic aromatic hydrocarbons, reduction of quinones, aromatic aldehydes and ketones, 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase activity of enzyme
-
-
-
additional information
?
-
biosynthesis and inactivation of steroid hormones, physiological role is to inactivate circulating androgens, progestins and glucocorticoids
-
-
-
additional information
?
-
-
inactivating circulating androgens, progestins and glucocorticoids. Regulation of hormone levels in endocrine target tissues and in carcinogen actibation
-
-
-
additional information
?
-
-
AKR1C9 catalyzes androgen, estrogen, and prostaglandin metabolism
-
-
-
additional information
?
-
-
C/EBPdelta regulates the AKR1C9 gene promoter in osteoblasts, overview
-
-
-
additional information
?
-
-
acetophenone derivatives are reduced enantioselectively by rat liver 3alpha-HSD to give (S)-alcohols
-
-
-
additional information
?
-
-
substrate specificty, overview, recombinant AKR1C17 efficiently oxidizes 3alpha-hydroxysteroids and diverse bile acids using NAD+ as the preferred coenzyme, no activity with progesterone, cortisone, and aldosterone. The enzyme also reduces non-steroidal alpha-dicarbonyl compounds such as 9,10-phenanethrenequinone, isatin, 6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one and diacetyl, but does not show significant activities towards 4-nitrobenzaldehyde and 4-nitroacetophenone
-
-
-
additional information
?
-
-
metabolizes androgens and glucocorticoids, function as a dihydrodiol dehydrogenase as well as 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase, enzyme catalyzes both oxidation and reduction reaction at physiological pH and is able to reduce aromatic ketones
-
-
-
additional information
?
-
-
involved in biosynthesis of bile acids
-
-
-
additional information
?
-
-
the enzyme displays a distinct preference for the reduction of quinones, e.g. 9,10-phenanthrenequinone, and 3-oxo steroids, e.g. androstane, pregnane and cholane, over aromatic aldehydes and ketones, whereas 3alpha-hydroxy steroids are overwhelmingly more efficiently oxidized than are 1-acenaphthenol or benzenedihydrodiol. Ethanol and 3beta-hydroxy steroids no substrates
-
-
-
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
2 tibolone + 2 NADPH + 2 H+
3alpha-hydroxytibolone + 3beta-hydroxytibolone + 2 NADP+
-
i.e. tibolone, a 3-ketosteroid androgen receptor, conversion to potent estrogen receptor alpha agonists, tibolone induces estrogen receptor alpha-dependent gene promoter activity through cis-acting estrogen response elements, increases the stimulatory effect of TGF-beta on Smad-dependent gene promoter activity, and enhances prostaglandin E2-induced activity of transcription factor Runx2, overview
3alpha-hydroxytibolone is the primary metabolite
-
r
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
-
i.e. 3alpha,5alpha-tetrahydroprogesterone or 3alpha,5alpha-THP, the enzyme catalyzes the biosynthesis and oxidation of 3alpha,5alpha-reduced neurosteroids as allopregnanolone, which stimulates GABAA receptors, sciatic nerves-induced analgesia results in increased enzyme levels in neuropathic rats, overview
-
-
r
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH + H+
-
steroid reduction direction is preferred
-
-
r
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
-
steroid reduction direction is preferred
-
-
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnan-3alpha-ol-20-one + NAD(P)+
-
regulation of the amount of allosteric agonists that can bind to the GABA receptor in brain
-
r
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione + NAD(P)H
5beta-pregnane-3alpha,17alpha,20beta,21-tetraol-11-one + NAD(P)+
-
hepatic reduction in animal tissues
-
?
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADPH
9-[hydroxy(phenyl)methyl]-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADP+
-
competitive substrate, fluorometric activity measurement in intact cells, overview
-
-
?
tibolone + NADPH
3-hydroxytibolone + NADP+
-
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
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
P23457
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
termination of androgen action
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
conversion in animal tissues
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
regulation of the amount of androgen in prostate, high levels of substrate are required for normal and abnormal growth of prostate
-
r
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
-
termination of androgen action
-
?
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
-
-
-
?
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
-
-
-
?
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
-
inactivation of the potent androgen in human prostate
-
-
r
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
-
inactivation of the potent androgen in human prostate, fluorometric activity measurement in intact cells, overview
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
P52895
androgen-inactivating enzyme
-
-
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
P52895
the enzyme is important in inactivation of DHT
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
the enzyme plays a crucial role in the regulation of the intracellular concentrations of testosterone and 5alpha-dihydrotestosterone, two steroids directly linked to the etiology and the progression of many prostate diseases and cancer, overview
-
-
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
-
-
-
?
additional information
?
-
P52895
the enzyme is important in the synthesis of neuroactive 5alpha/beta-pregnan-3alpha-ol-20-ones from their precursors, the enzyme plays a role in development and progression of prostate cancer
-
-
-
additional information
?
-
P52895
the RODH like 3alpha/17beta-HSD, EC 1.1.1.239, regulates the transactivation of AKR1C2, overview
-
-
-
additional information
?
-
-
AKR1C3 catalyzes androgen, estrogen, and prostaglandin metabolism, AKR1C3 is also involved in cancer development or progression
-
-
-
additional information
?
-
-
an androgen-inactivating enzyme, important in androgen and progesterone metabolism
-
-
-
additional information
?
-
P23457
biosynthesis and inactivation of steroid hormones, physiological role is to inactivate circulating androgens, progestins and glucocorticoids
-
-
-
additional information
?
-
-
inactivating circulating androgens, progestins and glucocorticoids. Regulation of hormone levels in endocrine target tissues and in carcinogen actibation
-
-
-
additional information
?
-
-
AKR1C9 catalyzes androgen, estrogen, and prostaglandin metabolism
-
-
-
additional information
?
-
-
C/EBPdelta regulates the AKR1C9 gene promoter in osteoblasts, overview
-
-
-
additional information
?
-
-
involved in biosynthesis of bile acids
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD+
-
preferred by AKR1C17, dependent on, residues Gln270 and Glu276 are important for cofactor specificity, overview
NADH
-
A-specific, hydride transfer occurs from the 4-pro-R-position of the cofactor to the C-3 position of the steroid
NADP+
-
preferred by AKR1C9, dependent on, residues Gln270 and Glu276 are important for cofactor specificity, overview
NADP+
-
loose association of the NADP(H) is followed by two conformational changes, which increases cofactor affinity by 86fold
NADPH
-
pro-R-hydrogen atom is transferred to the carbonyl substrate, A-specific
NADPH
-
loose association of the NADP(H) is followed by two conformational changes, which increases cofactor affinity by 86fold
additional information
-
dual pyridine nucleotide specificity, cofactor binding-site is located at the NH2 terminus
-
additional information
-
for a number of substrates the reactions are more efficient in the presence of NADPH and NADP+
-
additional information
-
4-pro-R-hydride transfer of the nicotinamide cofactor
-
additional information
-
4-pro-(R) hydrogen is transferred from the A-face of the cofactor to the B-face of the steroid
-
additional information
-
transfer of the 4-pro-R hydrogen from A-face of cofactor to the beta-face of the steroid substrate. Different binding modes for NAD(H) and NADP(H)
-
additional information
-
R276 plays an important role in cofactor binding
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
citrate
-
bound to the steroid-binding cavity via Tyr55 and His117, involved in the induced fit mechanism
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2E)-3-(4-bromophenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
93.3% inhibition at 0.1 mM
(2E)-3-(4-ethylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
89.1% inhibition at 0.1 mM
(2E)-3-(4-methylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
92.7% inhibition at 0.1 mM
(2E)-3-[4-(methylsulfanyl)phenyl]-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
93.5% inhibition at 0.1 mM
1-(4'nitrophenyl)prop-2-en-1-ol
-
inactivation dependent on NAD+ concentration, optimal at 0.5-1.0 mM NAD+, 2-mercaptoethanol prvides a concentration-dependent protection
1-(4'nitrophenyl)prop-2-en-1-one
-
inactivation can be retarded markedly in a concentration-dependent manner by both NADH and NADPH. Competitive inhibitor of NAD+ binding, measured for androsterone oxidation
1-(4'nitrophenyl)prop-2-yn-1-one
-
competitive inhibitor of NAD+ binding, measured for androsterone oxidation
1-(4-[[(2R)-2-methylpiperidin-1-yl]sulfonyl]phenyl)-1,3-dihydro-2H-pyrrol-2-one
-
IC50 value in HCT-116 cells engineered to over-express AKR1C3 is 11 nM
1-(4-[[(2R,6S)-2,6-dimethylpiperidin-1-yl]sulfonyl]phenyl)pyrrolidin-2-one
-
IC50 value in HCT-116 cells engineered to over-express AKR1C3 is 22 nM
1-[4-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)phenyl]pyrrolidin-2-one
-
IC50 value in HCT-116 cells engineered to over-express AKR1C3 is 24 nM
17beta-bromoacetoxy-5alpha-dihydrotestosterone
-
inactivation by modification of steroid-binding site
2'-hydroxyflavanone
-
most potent inhibitor, 0.02 mM inhibits by 98.9% and in an uncompetitive manner
2-(2,4-dioxo-1,3-thiazolidin-5-yl)-N-(2-hydroxyphenyl)acetamide
-
inhibitor is about 1000times more selective for isoform AKR1C3 over AKR1C2, and selectivity is even higher when compared with AKR1C1 and AKR1C4
3-((4-nitronaphthalen-1-yl)amino)benzoic acid
-
inhibitor nanomolar potency and selective inhibition of isoform AKR1C3 but also acts as an androgen receptor antagonist. It inhibits 5alpha-dihydrotestosterone stimulated androgen receptor reporter gene activity with an IC50 value of 4.7 microM and produces a concentration dependent reduction in androgen receptor levels in prostate cancer cells
3-phenoxybenzoic acid
-
inhibitor carboxylic acid binds to the oxyanion site, in which the carboxylate group very closely overlays the acetate molecule found in other AKR1C3 structures and forms hydrogen bonds to the enzyme catalytic residues His117 and Tyr55, as well as to a conserved water network located in and near the SP3 subpocket. The 3-phenoxy ring extends into the SP1 subpocket and makes van der Waals contacts with the aromatic residues Phe306, Phe311 and Tyr319 that line the pocket
3-[(4-nitrophenyl)amino]benzoic acid
-
94fold selectivity for the inhibition of isoform AKR1C3 over AKR1C2
3-[[4-(methoxymethyl)phenyl]amino]benzoic acid
-
360fold selectivity for the inhibition of isoform AKR1C3 over AKR1C2
3a-phenyl-2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one
-
inhibitor shows 17fold and 30fold selectivity against isoforms AKR1C2 and AKR1C1, respectively, and much higher selectivity against AKR1C4
4-androstene-3,17-dione
-
versus substrate, the products, 4-androstene-3,17-dione and NADH, inhibit the activity uncompetitively and competitively, respectively, with respect to NAD+ in the presence of a saturated concentration of 0.004 mM of the substrate
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one
-
competitive
acetylenic ketones
-
inactivation by forming Michael adducts with enzyme nucleophiles
-
celecoxib
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.050 mM in fluorometric assay, in vitro IC50: 0.050 mM in fluorometric assay
Cibacron blue
-
nucleotide analog, competitive with respect to NADP+, noncompetitive to androsterone
NADH
-
the products, 4-androstene-3,17-dione and NADH, inhibit the activity uncompetitively and competitively, respectively, with respect to NAD+ in the presence of a saturated concentration of 0.004 mM of the substrate
naphthalene-1,2-dione
-
naphthalene-1,2-dione leads to the time and concentration dependent irreversible inactivation of AKR1C9 via alkylation
naproxen
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.0094 mM in fluorometric assay, 0.016 mM in radiometric assay, in vitro IC50: 0.0027 mM in fluorometric assay
Phenolphthalein
-
AKR1C4-selective inhibitor, in vitro and in vivo inhibition, IC50: 0.0004 mM
ursodeoxycholate
-
natural inhibitor, in vivo IC50: 0.00024 mM in fluorometric assay, 0.00014 mM in radiometric assay, in vitro IC50: 0.000049 mM in fluorometric assay
3-[[4-(trifluoromethyl)phenyl]amino]benzoic acid
-
250fold selectivity for the inhibition of isoform AKR1C3 over AKR1C2
3-[[4-(trifluoromethyl)phenyl]amino]benzoic acid
-
in complex with AKR1C3. Compound adopts a similar binding orientation as flufenamic acid, however, its phenylamino ring projects deeper into a subpocket and confers selectivity over the other AKR1C isoforms
Flufenamic acid
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.0040 mM in fluorometric assay, in vitro IC50: 0.00031 mM in fluorometric assay
Hexestrol
-
hydroxysteroid analog, uncompetitive versus NADP+, competitive versus androsterone
Ibuprofen
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.017 mM in fluorometric assay, in vitro IC50: 0.009 mM in fluorometric assay
indomethacin
-
non-steroidal anti-inflamatory drug, uncompetitive against NAD+, competitive against androsterone
indomethacin
-
competitive, IC50 for reduction of 9,10-phenanthrenequinone is 0.000735 mM and of androsterone 0.00333 mM
p-chloromercuribenzoate
-
non-competitive with respect to dihydrocortisone 46-100% inhibition at 0.01 mM, preincubation with NADH lowers the inhibitory effect
Prostaglandin
-
A1, B1, E1, F1, F1alpha, A2, B2, E2 and F2alpha, inhibit 9,10-phenanthrenequinone reduction and androsterone oxidation, the order of inhibitory potency is related to their lipophilicity
additional information
-
no inhibition by the bile acid 5beta-cholanic acid-3alpha,7alpha-diol
-
additional information
-
dutasteride alters the expression level of the enzyme in breast cancer cells, the inhibitor affects the 5alpha-progesterone reductase and the progesterone metabolism, overview
-
additional information
-
is not inhibited by 0.02 mM caffeic acid, rutin, 4-hydroxybenzoic acid, cyanin chloride and taxifolin
-
additional information
-
not inhibited by dicoumarol, disulfiram and barbiturates. Inhibitory potency of non-steroidal anti-inflamatory drugs and salicylates falls sharply as the pH is increased from 6 to 9
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-butyl-3-methylimidazolium L-lactate
-
enhanced activity of 3alpha-hydroxysteroid dehydrogenase by addition of the co-solvent to 50 mM Tris-HCl buffer in aqueous phase of biphasic systems for reductive production of steroids. In a coupled-enzyme system comprising HSDH and formate dehydrogenase, a twofold increase in production rate of androsterone is obtained when utilizing 1-butyl-3-methylimidazolium L-lactate with NADH regeneration, overview
1-ethyl-3-methylimidazolium trifluoromethanesulfonate
-
addition of the co-solvent leads to slightly enhanced enzyme activity n an aqueous-organic solvent system with Tris-HCl buffer, overview
additional information
-
poor activation by 1-butyl-3-methylimidazolium trifluoromethanesulfonate and 1-butyl-3-methylimidazolium tetrafluoroborate
-
additional information
-
prostaglandin E2 increases AKR1C9 gene promoter activity and mRNA expression, AKR1C9 promoter activity is also enhanced by overexpression of protein kinase A catalytic subunit or transcription factor C/EBPdelta, whicb is reduced by dominant negative C/EBPdelta competition or C/EBPdelta antisense expression, overview
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma
Expression of dihydrodiol dehydrogenase and resistance to chemotherapy and radiotherapy in adenocarcinoma cells of lung.
Adenocarcinoma
[Gene expression profiling of human ovarian epithelial tumors by digo nucleotide microarray]
Breast Neoplasms
An indomethacin analogue, N-(4-chlorobenzoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3alpha-HSD, type 5 17beta-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone dependent and hormone independent malignancies.
Breast Neoplasms
Dutasteride affects progesterone metabolizing enzyme activity/expression in human breast cell lines resulting in suppression of cell proliferation and detachment.
Breast Neoplasms
Selective loss of AKR1C1 and AKR1C2 in breast cancer and their potential effect on progesterone signaling.
Breast Neoplasms
The role of progesterone metabolites in breast cancer: potential for new diagnostics and therapeutics.
Carcinoma
Dihydrodiol dehydrogenase in drug resistance and sensitivity of human carcinomas.
Carcinoma
Expression and characterization of recombinant type 2 3 alpha-hydroxysteroid dehydrogenase (HSD) from human prostate: demonstration of bifunctional 3 alpha/17 beta-HSD activity and cellular distribution.
Carcinoma
Expression of dihydrodiol dehydrogenase plays important roles in apoptosis- and drug-resistance of A431 squamous cell carcinoma.
Carcinoma
Increased expression of dihydrodiol dehydrogenase induces resistance to cisplatin in human ovarian carcinoma cells.
Carcinoma
Inverse expression of dihydrodiol dehydrogenase and glutathione-S-transferase in patients with esophageal squamous cell carcinoma.
Carcinoma
Sequence of the cDNA of a human dihydrodiol dehydrogenase isoform (AKR1C2) and tissue distribution of its mRNA.
Carcinoma
Ubiquitous induction of resistance to platinum drugs in human ovarian, cervical, germ-cell and lung carcinoma tumor cells overexpressing isoforms 1 and 2 of dihydrodiol dehydrogenase.
Carcinoma
[Gene expression profiling of human ovarian epithelial tumors by digo nucleotide microarray]
Carcinoma, Hepatocellular
Characterization of dihydrodiol dehydrogenase in rat H-4IIe hepatoma cells.
Carcinoma, Hepatocellular
Proteome analysis of rat hepatomas: carcinogen-dependent tumor-associated protein variants.
Carcinoma, Hepatocellular
Reduction of dihydrodiol dehydrogenase expression in resected hepatocellular carcinoma.
Carcinoma, Hepatocellular
The role of aryl hydrocarbon receptor in regulation of enzymes involved in metabolic activation of polycyclic aromatic hydrocarbons in a model of rat liver progenitor cells.
Carcinoma, Non-Small-Cell Lung
Expression of dihydrodiol dehydrogenase in the resected stage I non-small cell lung cancer.
Carcinoma, Non-Small-Cell Lung
Overexpression of dihydrodiol dehydrogenase as a prognostic marker of non-small cell lung cancer.
Carcinoma, Non-Small-Cell Lung
Proteomics-based identification of secreted protein dihydrodiol dehydrogenase as a novel serum markers of non-small cell lung cancer.
Carcinoma, Squamous Cell
Expression of dihydrodiol dehydrogenase plays important roles in apoptosis- and drug-resistance of A431 squamous cell carcinoma.
Colorectal Neoplasms
The long variant of human ileal bile acid-binding protein associated with colorectal cancer exhibits sub-cellular localization and lipid binding behaviour distinct from those of the common isoform.
Dupuytren Contracture
Common Variants of the ALDH2 and DHDH Genes and the Risk of Dupuytren's Disease.
Epilepsy
Characterization of the 5alpha-reductase-3alpha-hydroxysteroid dehydrogenase complex in the human brain.
Epilepsy
Expression of 5alpha-reductase and 3alpha-hydroxisteroid oxidoreductase in the hippocampus of patients with chronic temporal lobe epilepsy.
Epilepsy, Temporal Lobe
Expression of 5alpha-reductase and 3alpha-hydroxisteroid oxidoreductase in the hippocampus of patients with chronic temporal lobe epilepsy.
Esophageal Squamous Cell Carcinoma
Inverse expression of dihydrodiol dehydrogenase and glutathione-S-transferase in patients with esophageal squamous cell carcinoma.
Glaucoma
Altered expression of 3 alpha-hydroxysteroid dehydrogenases in human glaucomatous optic nerve head astrocytes.
Hepatoblastoma
Hepatocyte nuclear factor (HNF)-4 alpha/gamma, HNF-1 alpha, and vHNF-1 regulate the cell-specific expression of the human dihydrodiol dehydrogenase (DD)4/AKR1C4 gene.
Hirsutism
3{alpha}-Hydroxysteroid Dehydrogenase Type III Deficiency: A Novel Mechanism for Hirsutism.
Hypercholesterolemia
Identification of a novel hypocholesterolemic protein, major royal jelly protein 1, derived from royal jelly.
Hyperglycemia
Pathogenesis of diabetic neuropathy--do hyperglycemia and aldose reductase inhibitors affect neuroactive steroid formation in the rat sciatic nerves?
Infections
Infection of human papillomavirus and overexpression of dihydrodiol dehydrogenase in uterine cervical cancer.
Lung Neoplasms
A possible role for dihydrodiol dehydrogenase in the formation of benzo[a]pyrene-DNA adducts in lung cancer cells and tumor tissues.
Lung Neoplasms
Diagnostic value of serum dihydrodiol dehydrogenase 2 levels in patients with non-small-cell lung cancer.
Lung Neoplasms
Expression of dihydrodiol dehydrogenase in the resected stage I non-small cell lung cancer.
Lung Neoplasms
Overexpression of dihydrodiol dehydrogenase as a prognostic marker of non-small cell lung cancer.
Lung Neoplasms
Proteomics-based identification of secreted protein dihydrodiol dehydrogenase as a novel serum markers of non-small cell lung cancer.
Neoplasm Metastasis
Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects.
Neoplasm Metastasis
Hepatocyte growth factor and HER2/neu downregulate expression of apoptosis-inducing factor in non-small cell lung cancer.
Neoplasms
A possible role for dihydrodiol dehydrogenase in the formation of benzo[a]pyrene-DNA adducts in lung cancer cells and tumor tissues.
Neoplasms
An indomethacin analogue, N-(4-chlorobenzoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3alpha-HSD, type 5 17beta-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone dependent and hormone independent malignancies.
Neoplasms
Dihydrodiol dehydrogenases regulate the generation of reactive oxygen species and the development of cisplatin resistance in human ovarian carcinoma cells.
Neoplasms
Evaluation of the prognostic role of a panel of biomarkers in stage IB-IIIA non-small cell lung cancer patients.
Neoplasms
Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects.
Neoplasms
Glutathione-related enzymes contribute to resistance of tumor cells and low toxicity in normal organs to artesunate.
Neoplasms
Hepatocyte growth factor and HER2/neu downregulate expression of apoptosis-inducing factor in non-small cell lung cancer.
Neoplasms
Inhibition of 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) activity of human lung microsomes by genistein, daidzein, coumestrol and C(18)-, C(19)- and C(21)-hydroxysteroids and ketosteroids.
Neoplasms
Temporal and spatial patterns of ovarian gene transcription following an ovulatory dose of gonadotropin in the rat.
Neoplasms
Ubiquitous induction of resistance to platinum drugs in human ovarian, cervical, germ-cell and lung carcinoma tumor cells overexpressing isoforms 1 and 2 of dihydrodiol dehydrogenase.
Neoplasms
[Gene expression profiling of human ovarian epithelial tumors by digo nucleotide microarray]
Neoplasms, Germ Cell and Embryonal
Dihydrodiol dehydrogenases regulate the generation of reactive oxygen species and the development of cisplatin resistance in human ovarian carcinoma cells.
Neuralgia
The biological activity of 3alpha-hydroxysteroid oxido-reductase in the spinal cord regulates thermal and mechanical pain thresholds after sciatic nerve injury.
Optic Nerve Injuries
Altered expression of 3 alpha-hydroxysteroid dehydrogenases in human glaucomatous optic nerve head astrocytes.
Ovarian Neoplasms
Overexpression of dihydrodiol dehydrogenase is associated with cisplatin-based chemotherapy resistance in ovarian cancer patients.
Peripheral Nerve Injuries
Selective regulation of 3 alpha-hydroxysteroid oxido-reductase expression in dorsal root ganglion neurons: a possible mechanism to cope with peripheral nerve injury-induced chronic pain.
Pneumonia
Increased annexin A1 and A2 levels in bronchoalveolar lavage fluid are associated with resistance to respiratory disease in beef calves.
Prostatic Hyperplasia
Expression and characterization of recombinant type 2 3 alpha-hydroxysteroid dehydrogenase (HSD) from human prostate: demonstration of bifunctional 3 alpha/17 beta-HSD activity and cellular distribution.
Prostatic Hyperplasia
Function of human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase in androgen metabolism.
Prostatic Neoplasms
5alpha-androstane-3alpha,17beta-diol selectively activates the canonical PI3K/AKT pathway: a bioinformatics-based evidence for androgen-activated cytoplasmic signaling.
Prostatic Neoplasms
5alpha-androstane-3alpha,17beta-diol supports human prostate cancer cell survival and proliferation through androgen receptor-independent signaling pathways: implication of androgen-independent prostate cancer progression.
Stomach Neoplasms
Identification of genes differentially expressed between gastric cancers and normal gastric mucosa with cDNA microarrays.
Stomach Neoplasms
Overexpression of dihydrodiol dehydrogenase as a prognostic marker in resected gastric cancer patients.
Uterine Cervical Neoplasms
Infection of human papillomavirus and overexpression of dihydrodiol dehydrogenase in uterine cervical cancer.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0027
(5beta,20R)-20-hydroxypregnan-3-one
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.0021
5beta-androstane-3,17-dione
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.0024
5beta-pregnane-3,20-dione
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.023
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.003
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one
-
recombinant enzyme in intact COS-1 cells
0.004
Dehydrolithocholic acid
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.0012
17beta-hydroxy-5alpha-androstan-3-one
-
cloned human liver enzyme type I
0.0192
17beta-hydroxy-5alpha-androstan-3-one
-
cloned human liver enzyme type II
0.046
3alpha-hydroxy-5alpha-androstan-17-one
-
recombinant wild type enzyme
0.038
9,10-phenanthrenequinone
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
additional information
(11S,12S)-11,12-dihydrobenzo[g]chrysene-11,12-diol
-
racemic benzo[g]chrysene-11,12-dihydrodiol derived from the fjord-region parent hydrocarbon benzo[g]chrysene is oxidized with a kcat/Km of 1520 min/mM, which is more than 100 times greater than that observed with benzo[a]pyrene-7,8-dihydrodiol
additional information
benzo[a]pyrene-7,8-dihydrodiol
-
kcat/Km of 39 min/mM
additional information
additional information
-
transient-state and steady-state kinetics
-
additional information
additional information
-
steady-state kinetics
-
additional information
additional information
-
transient single and multiple turnover kinetics, stopped flow kinetics, isotope kinetics, ligand binding analysis, kinetics with deuterium-substituted cofactor and binary complex of enzyme and cofactor, overview
-
additional information
additional information
-
stereoselectivity, kinetics
-
additional information
additional information
-
equilibrium kinetics of wild-type and mutant enzymes
-
additional information
additional information
-
kinetics in absence and presence of co-solvents, overview
-
additional information
additional information
-
cofactor kinetics of wild-type and mutant enzymes, overview
-
additional information
additional information
-
steady-state, transient state kinetics, and kinetic isotope effects, kinetic analysis and mechanism, ordered bi-bi mechanism, detailed overview
-
additional information
additional information
-
kinetics of wild-type and mutant enzymes in presence or absence of CAPS and methylamine, overview
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00063 - 0.85
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
0.115
(5beta,20R)-20-hydroxypregnan-3-one
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.047
5beta-androstane-3,17-dione
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.105
5beta-pregnane-3,20-dione
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.1
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.00063
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
-
cofactor NADP+, pH 7.0, 25°C, steroid oxidation, recombinant mutant W227A
0.37
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
-
cofactor NADP+, pH 7.0, 25°C, steroid oxidation, recombinant wild-type enzyme
0.8
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
-
cofactor NADP+, pH 7.0, 25°C, steroid oxidation, recombinant mutant R276M
0.85
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
-
cofactor NAD+, pH 7.0, 25°C, steroid oxidation, recombinant wild-type enzyme
0.037
5alpha-dihydroprogesterone
-
cofactor NADPH, pH 7.0, 25°C, steroid reduction, recombinant mutant W227A
0.3
5alpha-dihydroprogesterone
-
cofactor NADPH, pH 7.0, 25°C, steroid reduction, recombinant wild-type enzyme
0.4
5alpha-dihydroprogesterone
-
cofactor NADPH, pH 7.0, 25°C, steroid reduction, recombinant mutant R276M
0.43
5alpha-dihydroprogesterone
-
cofactor NADH, pH 7.0, 25°C, steroid reduction, recombinant wild-type enzyme
0.183
9,10-phenanthrenequinone
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.83
androsterone
-
steady-state, pH 8.0, 25°C, recombinant wild-type enzyme
0.022
Dehydrolithocholic acid
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
additional information
additional information
-
single turnover, and multiple burst and steady-state in turnover, kinetic isotope effects with 4-pro-R-[2H]-NADPH on recombinant wild-type and mutant enzymes
-
additional information
additional information
-
kcat in steady-state, single turnover, burst in multiple turnover, steady-state in multiple turnover
-
additional information
additional information
-
cofactor kinetics of wild-type and mutant enzymes, overview
-
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000107
2-(2,4-dioxo-1,3-thiazolidin-5-yl)-N-(2-hydroxyphenyl)acetamide
-
pH 7.0, temperature not specified in the publication
0.00273
3a-phenyl-2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one
-
pH 7.0, temperature not specified in the publication
additional information
additional information
-
more Ki values given for different inhibitors of androsterone oxidation, 9,10-phenanthrenequinone- and 5alpha-androstane-3,17-dione reduction
-
0.00001
Cibacron blue
-
slope effect, 0.025 mM androsterone, varying NADP+ concentrations
0.0002
Cibacron blue
-
slope effect, 0.25 mM NADP+, varying androsterone concentrations
0.0005
Cibacron blue
-
intercept effect, 0.25 mM NADP+, varying androsterone concentrations
0.0029
Hexestrol
-
slope effect, 0.25 mM NADP+, varying androsterone concentrations
0.0031
Hexestrol
-
intercept effect, 0.025 mM androsterone, varying NADP+ concentrations
0.0002
indomethacin
-
competitive, for 9,10-phenanthrenequinone and 5alpha-androstane-3,17-dione reduction at pH 6.0
0.000835
indomethacin
-
competitive for androstene oxidation at pH 7.0. IC50 is 0.003 mM at H 7.0, 0.045 at pH 9.0
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0136
(2E)-3-(4-bromophenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.0136
(2E)-3-(4-ethylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.0134
(2E)-3-(4-methylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.0058
(2E)-3-[4-(methylsulfanyl)phenyl]-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000094
1-(4-[[(2R)-2-methylpiperidin-1-yl]sulfonyl]phenyl)-1,3-dihydro-2H-pyrrol-2-one
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000056
1-(4-[[(2R,6S)-2,6-dimethylpiperidin-1-yl]sulfonyl]phenyl)pyrrolidin-2-one
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000052
1-[4-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)phenyl]pyrrolidin-2-one
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000213
2-(2,4-dioxo-1,3-thiazolidin-5-yl)-N-(2-hydroxyphenyl)acetamide
Homo sapiens
-
pH 7.0, temperature not specified in the publication
0.0052
2-[[(3-hydroxyphenyl)carbonyl]amino]-4,5-dimethoxybenzoic acid
Homo sapiens
-
pH 7.0, temperature not specified in the publication
0.00084
2-[[(3-hydroxyphenyl)carbonyl]amino]-5-nitrobenzoic acid
Homo sapiens
-
pH 7.0, temperature not specified in the publication
0.08
3-((4-nitronaphthalen-1-yl)amino)benzoic acid
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000036
3-[(4-nitrophenyl)amino]benzoic acid
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000054
3-[[4-(methoxymethyl)phenyl]amino]benzoic acid
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.000062
3-[[4-(trifluoromethyl)phenyl]amino]benzoic acid
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.00546
3a-phenyl-2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one
Homo sapiens
-
pH 7.0, temperature not specified in the publication
0.0019
5-bromo-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
Homo sapiens
-
pH 7.0, temperature not specified in the publication
0.0022
5-chloro-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
Homo sapiens
-
pH 7.0, temperature not specified in the publication
0.05
celecoxib
Homo sapiens
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.050 mM in fluorometric assay, in vitro IC50: 0.050 mM in fluorometric assay
0.009
Ibuprofen
Homo sapiens
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.017 mM in fluorometric assay, in vitro IC50: 0.009 mM in fluorometric assay
0.0027
naproxen
Homo sapiens
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.0094 mM in fluorometric assay, 0.016 mM in radiometric assay, in vitro IC50: 0.0027 mM in fluorometric assay
0.0004
Phenolphthalein
Homo sapiens
-
AKR1C4-selective inhibitor, in vitro and in vivo inhibition, IC50: 0.0004 mM
0.000049
ursodeoxycholate
Homo sapiens
-
natural inhibitor, in vivo IC50: 0.00024 mM in fluorometric assay, 0.00014 mM in radiometric assay, in vitro IC50: 0.000049 mM in fluorometric assay
0.00031
Flufenamic acid
Homo sapiens
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.0040 mM in fluorometric assay, in vitro IC50: 0.00031 mM in fluorometric assay
0.000735
indomethacin
Rattus norvegicus
-
competitive, IC50 for reduction of 9,10-phenanthrenequinone by NADPH at pH6.0 is 0.000735 mM
0.00333
indomethacin
Rattus norvegicus
-
competitive, IC50 for oxidation of androsterone by NAD+ at pH 7.0 0.00333 mM
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0005 - 0.0053
-
for prostaglandins A1, A2, B1, B2, D2, E1, E2, F1, F2alpha at concentrations of 0.06 mM
0.0007 - 0.0012
-
for 15-keto-prostaglandins E2 and F2alpha at concentrations of 0.06 mM
0.008 - 4
-
determined for several substrates,with best activities for 9,10-phenanthrenequinone, 4-nitrobezaldehyde and androsterone
0.07
-
recombinant AKR1C17 in cell extract, substrate 4-androsten-3alpha-ol-17-one
0.08
0.1
0.23
-
purified recombinant AKR1C17, substrate 4-androsten-3alpha-ol-17-one
1.6
additional information
additional information
-
enzyme contains conserved catalytic tetrad of Asp50, Tyr55, Lys84 and His117
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5 - 11
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
brenda
-
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
the enzyme expression is positively correlated to adiposity in woman
brenda
-
high expression and activity in astrocytes of glaucomatous optic nerve head
brenda
-
uniform, diffuse, and strong expression of isoform AKR1C3 in normal endometrial epithelium but not in endometrial stromal cells. The expression of AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium
brenda
-
uniform, diffuse, and strong expression of isoform AKR1C3 in normal endometrial epithelium but not in endometrial stromal cells. The expression of AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium
brenda
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
brenda
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
brenda
-
strong isoform AKR1C3 immunoreactivity in columnar epithelium but only weak immunoreactivity in squamous epithelium of the gastrointestinal junction
brenda
-
primary, high expression and activity in healthy hepatocytes
brenda
-
strong isoform AKR1C3 immunoreactivity in bronchial epithelium but not in bronchial glands or alveolar pneumocytes
brenda
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
brenda
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
brenda
-
6fold higher expression level in female than in male pituitary
brenda
-
lumbar, of naive, sham-operated and neuropathic rats, enzyme expression analysis and cellular distribution in neurons and glial cells, immunohistochemic analysis, overview
brenda
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
brenda
additional information
-
the urothelial epithelium lining the renal pelvis is strongly immunoreactive, but stromal cells in the underlying supporting connective tissue are negative
brenda
-
only a small number of epithelial cells are immunoreactive with both nuclear and cytoplasmic reactivity
brenda
-
no activity in the stromal cells or endothelial cells, but weak immunoreactivity in the epididymal epithelial cells
brenda
-
in renal cortex, endothelial cells of the glomeruli lack immunoreactivity for AKR1C3, but the Bowman’s capsule and mesangial cells are strongly reactive, as well as larger epithelial cells of the medulla, overview
brenda
-
specific expression of AKR1C17, two enzymes are expressed more highly in renal cortex than in the medulla
brenda
-
-
347979, 347980, 347981, 347982, 347985, 347988, 347989, 347990, 673101, 673349, 685529, 687635, 697310, 722157
brenda
in primary prostate stromal cells, co-localization with RODH like 3alpha/17beta-HSD, EC 1.1.1.239
brenda
-
epithelial cells, but not the stromal cells or endothelial cells
brenda
-
in Leydig cells, but no or poor activity in germ cells and Sertoli cells
brenda
additional information
-
tissue distribution of AKR1C3, immunohistochemic analysis, overview
brenda
additional information
-
no isoform AKR1C3 immunoreactivity in bronchial glands or alveolar pneumocytes and small cell carcinoma of the lung, only weak immunoreactivity in squamous epithelium of the gastrointestinal junction
brenda
additional information
-
the androgen-inactivating enzyme is selectively expressed in female tissue, while it is mostly absent in male tissue, tissue distribution, overview
brenda
additional information
-
indomethacin-sensitive 3alpha-hydroxysteroid dehydrogenase widely distributed in prostate, spleen, heart, testis, small intestine, stomach, lung and brain
brenda
additional information
-
low activities found in dog and rabbit liver, no significant activities are detected in extracts of beef, hog, guinea pig, mouse and human liver
brenda
additional information
-
tissue distribution of AKR1C9, immunohistochemic analysis, overview
brenda
additional information
-
indomethacin-sensitive 3alpha-hydroxysteroid dehydrogenase widely distributed in prostate, spleen, heart, testis, small intestine, stomach, lung and brain
-
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
additional information
-
tissue-dependent subcellular localization, overview
-
brenda
additional information
-
subcellular localization of isozymes, overview
-
brenda
additional information
-
tissue-dependent subcellular localization, overview
-
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
comparison of a common non-synonymous polymorphism, AKR1C3-2 in the gene encoding the enzyme 3alpha-HSD2/17beta-HSD5 and a synonymous SNP, rs248793, in SRD5A1, which encodes 5alpha-reductase: for caucasian males, carriers of the alcohol dependence-protective AK1C3-2 G-allele have higher levels of 5alpha-androstane-3alpha1beta-diol relative to the precursor 3alpha,5alpha-androsterone than C-allele homozygotes. AKR1C3-2 G-allele carriers exhibit greater increases in heart rate and stimulant and sedative effects of alcohol than C-allele homozygotes
physiological function
physiological function
-
exposure of HCT-15 cells to cisplatin results in aquisition of cisplatin resistance and concomitant induction of isoform AKR1C3 and aldo-keto reductase AKR1C1 expression. The resistance lowers the sensitivity toward cellular damages evoked by oxidative stress-derived aldehydes, 4-hydroxy-2-nonenal and 4-oxo-2-nonenal that are detoxified by AKR1C1 and AKR1C3. Overexpression of AKR1C1 or AKR1C3 in the parental HCT15 cells mitigates the cytotoxicity of the aldehydes and cisplatin. Knockdown of both AKR1C1 and AKR1C3 in the resistant cells or treatment of the cells with specific inhibitors of the aldo-keto reductases increases the sensitivity to ciplatin toxicity
physiological function
-
in LNCaP and LNCaP-AKR1C3 cells overexpressing isoform AKR1C3, metabolism proceeds via 5alpha-reduction to form 5alpha-androstane-3,17-dione and then (epi)androsterone-3-glucuronide. LNCaP-AKR1C3 cells make significantly higher amounts of testosterone-17beta-glucuronide. When 5alpha-reductase is inhibited by finasteride, the production of testosterone-17beta-glucuronide is further elevated in LNCaP-AKR1C3 cells. When AKR1C3 activity is inhibited with indomethacin the production of testosterone-17beta-glucuronide is significantly decreased. 4-Androstene-3,17-dione treatment stimulates cell proliferation in both cell lines. LNCaP-AKR1C3 cells are resistant to the growth inhibitory properties of finasteride, consistent with the diversion of 4-androstene-3,17-dione metabolism from 5alpha-reduced androgens to increased formation of testosterone
physiological function
-
the enzyme 3alpha-hydroxysteroid dehydrogenase is involved in neuroactive steroid biosynthesis. Genetic variation in a region of chromosome 10 containing the genes AKR1C1, AKR1C3 and AKR1C4, which encode 3 isoforms of 3alpha-HSD, is associated with variation in subjective alcohol response. Enzyme mutant variant H5Q is associated with reduced risk of both alcohol dependence and bladder cancer, moderates the stimulant or sedative effects of alcohol
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
Sequence
A0A0H3KPN5_BURM1
Burkholderia multivorans (strain ATCC 17616 / 249)
268
0
28987
TrEMBL
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
32000
-
x * 32000, about, recombinant His-tagged wild-type and mutant enzymes, SDS-PAGE
33000
34000
37000
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
monomer
tetramer
additional information
?
-
x * 32000, about, recombinant His-tagged wild-type and mutant enzymes, SDS-PAGE
dimer
-
the dimerization takes place via an interface axis. The formation of a tetramer is blocked in 3alpha-HSD/CR by the presence of a predominantly alpha-helical subdomain which is missing in all other SDRs of known structure, overview
monomer
-
1 * 33000 gel filtration; 1 * 34000 SDS-PAGE; 1 * 34000 SDS-PAGE
-
additional information
-
domain structure, the enzyme possessses a 28 amino acids insertion into the classical Rossmann-fold motif between strand betaE and helix alphaF, preventing the formation of a four helix bundle and enables the dimerization via a P-axis interface, structure homology modelling and simulation, structure comparison, overview
additional information
-
comparison of the folding topologies found in the crystal structures of the holo-enzyme and the apo-enzyme, structural changes in solution, overview
additional information
-
comparison of the folding topologies found in the crystal structures of the holo-enzyme and the apo-enzyme, structural changes in solution, overview
-
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CRYSTALLIZATION/commentary
ORGANISM
UNIPROT
LITERATURE
10 ns molecular dynamics simulations of inhibitor bound to isofrom AKR1C3. Binding could induce conformational changes to both inhibitor and enzyme. The compound presumably assumes a stable, energetically favored, planar conformation, with an estimated free energy of binding of -5 kcal/mol
-
docking of inhibitors (2E)-3-(4-methylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid, (2E)-3-(4-ethylphenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid, (2E)-3-(4-bromophenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid and (2E)-3-[4-(methylsulfanyl)phenyl]-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid to crystal structure. Compounds occupy a similar position of the active site as the co-crystallized indomethacin, with the Aryl1 overlapping with the p-chlorobenzoyl moiety of the indomethacin and the Aryl2 overlapping with an indole part of the indomethacin
-
in complex with 3-phenoxybenzoic acid, to 1.68 A resolution, space group P212121
-
in complex with inhibitor 1-(4-[[(2R)-2-methylpiperidin-1-yl]sulfonyl]phenyl)-1,3-dihydro-2H-pyrrol-2-one. The 2-pyrrolidinone does not interact directly with residues in the oxyanion hole
-
in complex with inhibitor 3-[[4-(trifluoromethyl)phenyl]amino]benzoic acid. Compound adopts a similar binding orientation as flufenamic acid, however, its phenylamino ring projects deeper into a subpocket and confers selectivity over the other AKR1C isoforms
-
purified recombinant wild-type enzyme, hanging drop vapour diffusion method, 4°C, mixing of equal volumes of 14 mg/ml protein solution and mother liquor containing 0.1 M sodium citrate, pH 6.5, 0.1 M ammonium acetate, and 24-30% PEG 4000, cryoprotection of crystals in 20% ethylene glycol in mother liquor, X-ray diffraction structure determination and analysis at 1.9 A resolution, molecular replacement study
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purified enzyme with NADH, hanging drop vapour diffusion method, 4°C, in presence of 1.4 M ammonium sulfate, 0.14 M NaCl, and 0.1 M Tris, pH 9.0, rod cluster crystals appear within 1 week, X-ray diffraction structure determination and analysis at 1.8 A resolution, modeling
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K159A
K159M
-
site-directed mutagenesis, the mutation changes the rate-limiting step to the hydride transfer, proton transfer is blocked in the mutant but can be rescued using exogenous proton acceptors, such as buffers, small primary amines, and azide, overview
S114A
-
site-directed mutagenesis, altered kinetics in comparison to the wild-type enzyme
S114A/Y155F
-
site-directed mutagenesis, altered kinetics in comparison to the wild-type enzyme
Y155F
-
site-directed mutagenesis, altered kinetics in comparison to the wild-type enzyme
Y155F/K159A
-
site-directed mutagenesis, altered kinetics in comparison to the wild-type enzyme