Information on EC 1.1.1.213 - 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific)

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY
1.1.1.213
-
RECOMMENDED NAME
GeneOntology No.
3alpha-hydroxysteroid 3-dehydrogenase (Re-specific)
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
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+
show the reaction diagram
bi bi mechanism, pyridine nucleotide binds first and leaves last; binding and release or pyridine is rate-limiting
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
bi bi mechanism, pyridine nucleotide binds before substrate
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
ordered and sequential mechanism, nucleotide binds first and leaves last
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
short-chain alcohol/polyol dehydrogenase family
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
aldoketoreductase superfamily; bi bi mechanism, pyridine nucleotide binds before substrate
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
aldoketoreductase superfamily; bi bi mechanism, pyridine nucleotide binds first and leaves last
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
aldoketoreductase superfamily; bi bi mechanism, pyridine nucleotide binds first and leaves last; ordered and sequential mechanism, nucleotide binds first and leaves last
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
ordered bi bi reaction mechanism
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
catalytic triad residues Ser114, Tyr155, and Lys159 have mechanistic roles in the catalytic reaction
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
the reduction reaction is slightly preferred by the wild-type enzyme, which is determined by residue Arg276
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
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
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
the enzyme shows a sequential ordered reaction mechanism, where NAD+ binds to the enzyme first and NADH leaves last
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
bi bi ordered mechanism, kinetic analysis, overview
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
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
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
short-chain alcohol/polyol dehydrogenase family
Eubacterium sp. VPI 12708
-
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
bi bi mechanism, pyridine nucleotide binds before substrate; ordered and sequential mechanism, nucleotide binds first and leaves last
Rattus norvegicus Sprangue-Dawley
-
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
oxidation
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
bile acid biosynthesis, neutral pathway
-
Steroid hormone biosynthesis
-
testosterone and androsterone degradation to androstendione
-
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.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
17beta-hydroxysteroid dehydrogenase type 5
-
-
3-alpha hydroxysteroid oxidoreductase
-
-
3-alpha-HSO
-
-
3alpha-HSD
P52895
-
3alpha-HSD type 3
P52895
-
3alpha-HSD3
-
-
3alpha-HSOR
-
-
3alpha-hydroxysteroid dehydrogenase
-
-
-
-
3alpha-hydroxysteroid dehydrogenase
-
-
3alpha-hydroxysteroid dehydrogenase
P52895
-
3alpha-hydroxysteroid dehydrogenase
-
-
3alpha-hydroxysteroid dehydrogenase
-
-
3alpha-hydroxysteroid dehydrogenase
-
-
-
3alpha-hydroxysteroid dehydrogenase
-
-
3alpha-hydroxysteroid dehydrogenase (B-specific)
-
-
-
-
3alpha-hydroxysteroid dehydrogenase type 2
-
-
3alpha-hydroxysteroid dehydrogenase/carbonyl reductase
-
-
3alpha-hydroxysteroid oxido-reductase
-
-
3alpha-hydroxysteroid oxidoreductase
-
-
-
-
3alpha-hydroxysteroid:NAD(P) oxidoreductase
-
-
-
-
3alphaHSD
-
-
3alphaHSD
-
-
-
3alphaHSD
-
-
A-specific 3alpha-hydroxysteroid dehydrogenase
-
-
-
-
AKR1C2
P52895
-
AKR1C4
-
-
AKR1C9
P23457
-
alpha-HSD/CR
-
-
B-specific 3alpha-hydroxysteroid dehydrogenase
-
-
-
-
bile acid-binding protein
P52895
-
DD2
P52895
-
dihydrodiol dehydrogenase
P23457
-
NAD+-dependent 3alpha-HSD
-
-
NADP(H)-dependent 3alpha-HSD
-
-
type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase
-
-
type 3 3-alpha-hydroxysteroid dehydrogenase
P52895
-
type 3 3alpha-HSD
P52895
-
type 3 3alpha-hydroxysteroid dehydrogenase
-
-
type 5 beta-hydroxysteroid dehydrogenase
P42330
-
additional information
-
cf. EC 1.1.1.50
additional information
-
cf. EC 1.1.1.50, the enzyme belongs to the short chain dehydrogenase/reductase protein superfamily
additional information
-
the enzyme belongs to the short-chain dehydrogenase/reductase family
additional information
-
cf. EC 1.1.1.239, the enzyme belongs to the AKR1C subfamily
additional information
-
cf. EC 1.1.1.50
additional information
-
cf. EC 1.1.1.50, the enzyme belongs to the aldo-keto reductase subfamily AKR1C
additional information
-
cf. EC 1.1.1.50, the enzyme belongs to the aldo-keto reductase, AKR, superfamily
additional information
P52895
the enzyme is a member of the aldo-keto reductase family
additional information
-
cf. EC 1.1.1.50, the enzyme belongs to the AKR1C family
additional information
-
cf. EC 1.1.1.50, the enzyme belongs to the AKR1C family
-
additional information
-
cf. EC 1.1.1.50
additional information
-
cf. EC 1.1.1.50, the enzyme belongs to the short-chain dehydrogenase/reductase family
additional information
-
cf. EC 1.1.1.50, the enzyme is a member of the aldo-keto reductase superfamily
additional information
-
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
P23457
the enzyme belongs to the aldo-keto reductase gene family
CAS REGISTRY NUMBER
COMMENTARY
9028-56-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
strain VPI 12708
-
-
Manually annotated by BRENDA team
Eubacterium sp. VPI 12708
strain VPI 12708
-
-
Manually annotated by BRENDA team
gene AKR1C2 or DDH2
SwissProt
Manually annotated by BRENDA team
golden hamster, adult, male
-
-
Manually annotated by BRENDA team
strain B-0831
-
-
Manually annotated by BRENDA team
strain B-0831
-
-
Manually annotated by BRENDA team
female Wistar rats
-
-
Manually annotated by BRENDA team
isozyme AKR1C9
-
-
Manually annotated by BRENDA team
male sprague-dawley rats
-
-
Manually annotated by BRENDA team
male Wistar rats
-
-
Manually annotated by BRENDA team
male, adult; Sprangue-Dawley
-
-
Manually annotated by BRENDA team
male; Sprangue-Dawley
-
-
Manually annotated by BRENDA team
Sprangue-Dawley
-
-
Manually annotated by BRENDA team
Wistar, 7-13 weeks old
-
-
Manually annotated by BRENDA team
Rattus norvegicus Sprangue-Dawley
Sprangue-Dawley
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
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
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(11S,12S)-11,12-dihydrobenzo[g]chrysene-11,12-diol + NADP+
? + NADPH + H+
show the reaction diagram
-
enzyme is stereoselective for benzo[g]chrysene-11S,12S-dihydrodiol
-
-
?
(S)-alpha-tetralol + NADP+
alpha-tetralone + NADPH + H+ [View the structure]
show the reaction diagram
-
-
-
-
?
(S)-tetralol + NADP+
? + NADPH
show the reaction diagram
-
-
-
-
?
1-(4'nitrophenyl)prop-2-en-1-ol + NAD+
1-(4'nitrophenyl)prop-2-en-1-one + NADH
show the reaction diagram
Rattus norvegicus, Rattus norvegicus Sprangue-Dawley
-
-
-
?
1-(4'nitrophenyl)prop-2-yn-1-ol + NAD+
1-(4'nitrophenyl)prop-2-yn-1-one + NADH
show the reaction diagram
Rattus norvegicus, Rattus norvegicus Sprangue-Dawley
-
-
-
?
1-acenaphthenol + NAD(P)+
1-acenaphthenone + NAD(P)+
show the reaction diagram
Rattus norvegicus, Rattus norvegicus Sprangue-Dawley
-
pH 9.0
-
?
1-acenaphthenol + NADPH
?
show the reaction diagram
-
-
-
-
?
1-acetophenone + NADPH
1-phenylethanol + NADP+
show the reaction diagram
-
-
-
-
?
1-indanone + NADPH
?
show the reaction diagram
-
-
-
-
?
10-oxonortriptyline + NADPH
?
show the reaction diagram
P52895
-, a drug acting as substrate
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
-
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)+
show the reaction diagram
-
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
P23457
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
-
termination of androgen action
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
-
conversion in animal tissues
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
-
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)+
show the reaction diagram
Rattus norvegicus Sprangue-Dawley
-
termination of androgen action
-
?
17beta-hydroxy-5alpha-androstan-3-one + NADPH
3alpha,17beta-dihydroxy-5alpha-androstan + NADP+
show the reaction diagram
-
-
-
r
2 tibolone + 2 NADPH + 2 H+
3alpha-hydroxytibolone + 3beta-hydroxytibolone + 2 NADP+
show the reaction diagram
-
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+
show the reaction diagram
-
i.e. tibolone, a 3-ketosteroid androgen receptor, conversion to potent estrogen receptor alpha agonists, overview
3alpha-hydroxytibolone is the primary metabolite
-
r
2-acetylpyridine + NADPH
1-(2-pyridyl)ethanol + NADP+
show the reaction diagram
-
stereoselective catalysis producing mainly the (S)-alcohols
-
-
?
2-decalone + NADH
? + NAD+
show the reaction diagram
-
pH 6.0
-
?
3-acetylpyridine + NADPH
1-(3-pyridyl)ethanol + NADP+
show the reaction diagram
-
low activity, stereoselective catalysis producing mainly the (S)-alcohols
-
-
?
3-ketosteroids + NADPH
3-hydroxysteroids + NADP+
show the reaction diagram
P52895
-
-
-
?
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
show the reaction diagram
-
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, i.e. 3alpha,5alpha-tetrahydroprogesterone or 3alpha,5alpha-THP
-
-
r
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH + H+
show the reaction diagram
-
steroid reduction direction is preferred
-
-
r
3alpha-hydroxy-5alpha-androstan-17-one + NAD+
5alpha-androstan-3,17-dione + NADH
show the reaction diagram
-
-
-
r
3alpha-hydroxy-5alpha-androstan-17-one + NAD+
5alpha-androstan-3,17-dione + NADH
show the reaction diagram
-
-
-
r
3alpha-hydroxy-5alpha-androstan-17-one + NAD+
5alpha-androstan-3,17-dione + NADH
show the reaction diagram
-
-
-
r
3alpha-hydroxy-5alpha-androstan-17-one + NAD+
5alpha-androstan-3,17-dione + NADH
show the reaction diagram
Rattus norvegicus, Rattus norvegicus Sprangue-Dawley
-
pH 9.0
-
-
3alpha-hydroxy-5alpha-androstan-17-one + NADP+
5alpha-androstan-3,17-dione + NADPH
show the reaction diagram
-
-
-
r
3alpha-hydroxy-5alpha-androstan-17-one + NADP+
5alpha-androstan-3,17-dione + NADPH
show the reaction diagram
-
-
-
r
4'-methoxyacetophenone + NADPH + H+
1-(4-methoxyphenyl)ethanol + NADP+
show the reaction diagram
-
-
-, R,S-enantiomeric product
-
?
4-acetylpyridine + NADPH
(S)-1-(4-pyridyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
4-acetylpyridine + NADPH
1-(4-pyridyl)ethanol + NADP+
show the reaction diagram
-
stereoselective catalysis producing mainly the (S)-alcohols
-
-
?
4-androsten-3alpha-ol-17-one + NADH + H+
4-androsten-3alpha,17beta-diol + NAD+
show the reaction diagram
-
AKR1C17
-
-
r
4-androstene-3,17-dione + NADH + H+
4-androsten-3alpha-ol-17-one + NAD+
show the reaction diagram
-
low activity
-
-
r
4-bromoacetophenone + NADPH + H+
1-(4-bromophenyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
4-cyanoacetophenone + NADPH + H+
1-(4-cyanophenyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
4-hydroxynonenal + NADPH
?
show the reaction diagram
-
-
-
-
?
4-methylacetophenone + NADPH + H+
1-(4-methylphenyl)ethanol + NADP+
show the reaction diagram
-
-
R,S-enantiomeric product
-
?
4-nitroacetophenone + NAD(P)H
1-(4-nitrophenyl)ethanol + NAD(P)+
show the reaction diagram
-
pH 6.0
-
?
4-nitroacetophenone + NADPH + H+
1-(4-nitrophenyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
4-nitrobenzaldehyde + NAD(P)H
(4-nitrophenyl)methanol + NAD(P)+
show the reaction diagram
-
pH 6.0
-
-
4-nitrobenzaldehyde + NAD(P)H
(4-nitrophenyl)methanol + NAD(P)+
show the reaction diagram
-
pH 6.0
-
?
4-nitrobenzaldehyde + NAD(P)H
(4-nitrophenyl)methanol + NAD(P)+
show the reaction diagram
-
NADH as cofactor
-
-
4-oxo-2-nonenal + NADPH + H+
4-hydroxynonenal + NADP+
show the reaction diagram
-
-
-
-
?
5alpha-androstan-17beta-ol-3-one + NADPH + H+
5alpha-androstan-3alpha,17beta-diol + NADP+
show the reaction diagram
-
-
-
?
5alpha-androstan-3,17-dione + NAD(P)H
3alpha-hydroxy-5alpha-androstan-17-one + NAD(P)+
show the reaction diagram
P23457
-
-
r
5alpha-androstan-3,17-dione + NAD(P)H
3alpha-hydroxy-5alpha-androstan-17-one + NAD(P)+
show the reaction diagram
Rattus norvegicus, Rattus norvegicus Sprangue-Dawley
-
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+
show the reaction diagram
-
-
-
-
r
5alpha-androstan-3alpha-ol-17-one + NADH + H+
5beta-androstan-3alpha,17beta-diol + NAD+
show the reaction diagram
-
-
-
-
-
5alpha-androstane-3,17-dione + NADH
5alpha-androstan-3alpha-ol-17-one + NAD+
show the reaction diagram
-
low activity
AKR1C9
-
r
5alpha-androstane-3alpha,17beta-diol + NADP+
5alpha-androstane-17beta-ol-3-one + NADPH
show the reaction diagram
-
-
-
r
5alpha-androstanedione + NADPH
5alpha-pregnan-3alpha-ol-20-one + NADP+
show the reaction diagram
-
-
i.e. allopregnanolone
-
?
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
-
-
-
-
?
5alpha-dihydrotestosterone + NADH
?
show the reaction diagram
-
low activity
-
-
?
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
show the reaction diagram
-
inactivation of the potent androgen in human prostate
-
-
r
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
show the reaction diagram
-
inactivation of the potent androgen in human prostate, fluorometric activity measurement in intact cells, overview, i.e. DHT
-
-
?
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
show the reaction diagram
-
i.e. DHT
-
-
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
-
-
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
P52895
androgen-inactivating enzyme
-
-
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
P52895
the enzyme is important in inactivation of DHT
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
-
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+
show the reaction diagram
-
i.e. DHT
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
P52895
i.e. DHT
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
-
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
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
-
i.e. DHT, substrate and cofactor binding site structure
-
-
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
P52895
i.e. DHT, the enzyme prefers the reductive reaction
-
-
r
5alpha-dihydrotestosterone + NADPH + H+
3alpha-androstanediol + NADP+
show the reaction diagram
-
steroid reduction direction is preferred, the chemical oxidation step is rate-limiting, W227 is very important for cataylsis, steroid reduction direction is preferred
-
-
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnan-3alpha-ol-20-one + NAD(P)+
show the reaction diagram
-
regulation of the amount of allosteric agonists that can bind to the GABA receptor in brain
-
r
5alpha-pregnan-3alpha,21-diol-20-one + NADP+
5alpha-pregnan-21-ol-3,20-dione + NADPH
show the reaction diagram
-
-
-
r
5alpha-pregnane-20alpha-ol-3-one + NADH
5alpha-pregnane-3,20alpha-diol + NAD+
show the reaction diagram
-
-
-
-
?
5alpha-pregnane-3,20-dione + NADH
5alpha-pregnan-3alpha-ol-20-one + NAD+
show the reaction diagram
-
low activity
-
-
r
5beta-androstan-3alpha-ol-17-one + NAD(P)+
5beta-androstane-3,17-dione + NAD(P)H
show the reaction diagram
-
-
-
-
r
5beta-androstan-3alpha-ol-17-one + NADH
5beta-androstane-3alpha,17beta-diol + NAD+
show the reaction diagram
-
-
-
-
r
5beta-androstan-3alpha-ol-17-one + NADP+
5beta-androstan-3,17-dione + NADPH
show the reaction diagram
-
-
-
?
5beta-androstane-3,17-dione + NADH
5beta-androstan-3alpha-ol-17-one + NAD+
show the reaction diagram
-
-
-
-
r
5beta-androstane-3alpha,17beta-diol + NADP+
5beta-androstane-17beta-ol-3-one + NADPH
show the reaction diagram
-
-
-
r
5beta-cholestane-3alpha,7alpha,12alpha-triol + NADP+
7alpha,12alpha-dihydroxy-5beta-cholestan-3-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
5beta-cholestane-3alpha,7alpha-diol + NADP+
7alpha-hydroxy-5beta-cholestan-3-one + NADPH + H+
show the reaction diagram
-
-
-
-
?
5beta-dihydrocortisone + NADPH
3alpha,17alpha,21-trihydroxy-5beta-pregnan-11,20-dione + NADP+
show the reaction diagram
-
-
-
?
5beta-pregnan-3alpha-ol-20-one + NAD(P)+
5beta-pregnane-3,20-dione + NAD(P)H
show the reaction diagram
-
-
-
-
r
5beta-pregnan-3alpha-ol-20-one + NADP+
5beta-pregnane-3,20-dione + NADPH
show the reaction diagram
-
-
-
r
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione + NAD(P)H
5beta-pregnane-3alpha,17alpha,20beta,21-tetraal-11-one + NAD(P)+
show the reaction diagram
-
-
-
r
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione + NAD(P)H
5beta-pregnane-3alpha,17alpha,20beta,21-tetraal-11-one + NAD(P)+
show the reaction diagram
-
hepatic reduction in animal tissues
-
?
5beta-pregnane-20alpha-ol-3-one + NADH + H+
5beta-pregnane-3,20alpha-diol + NAD+
show the reaction diagram
-
-
-
-
?
5beta-pregnane-3,20-dione + NADH + H+
5beta-pregnan-3alpha-ol-20-one + NAD+
show the reaction diagram
-
-
-
-
r
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one + NADH
?
show the reaction diagram
-
the enzyme produces both R- and S-form products in a ratio of 2.3 : 1
-
-
?
9,10-phenanthrenequinone + NAD(P)H
? + NAD(P)+
show the reaction diagram
-
NADPH
-
?
9,10-phenanthrenequinone + NAD(P)H
? + NAD(P)+
show the reaction diagram
-
pH 6.0
-
?
9,10-phenanthrenequinone + NAD(P)H
? + NAD(P)+
show the reaction diagram
-
pH 6.0
-
?
9,10-phenanthrenequinone + NADH
?
show the reaction diagram
-
-
-
-
?
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+
show the reaction diagram
-
competitive substrate, fluorometric activity measurement in intact cells, overview, competitive substrate
-
-
?
acetohexamide + NADPH
?
show the reaction diagram
P52895
-, a drug acting as substrate
-
-
?
acetophenone + NADPH
1-phenylethanol + NADP+
show the reaction diagram
-
-
-
-
?
androstan-17beta-ol-3-one + NADH
androstan-3alpha,17beta-diol + NAD+
show the reaction diagram
-
-
-
?
androstan-3,17-dione + NADH
androstan-3alpha-ol-17-one + NAD+
show the reaction diagram
-
-
-
?
androsterone + NAD(P)+
5alpha-androstane-3,17-dione + NAD(P)H
show the reaction diagram
-
-
-
-
r
androsterone + NAD+
androstanedione + NADH
show the reaction diagram
-
-
-
-
r
androsterone + NAD+
androstanedione + NADH
show the reaction diagram
-
the intramolecular proton transfer is a rate-limiting step, with a concomitant releasing of protons to bulk solvent
-
-
r
androsterone + NAD+
5alpha-androstane-3,17-dione + NADH
show the reaction diagram
-
-
-
-
r
androsterone + NADP+
5alpha-androstane-3,17-dione + NADPH
show the reaction diagram
-
-
-
-
r
befunolol + NADPH
?
show the reaction diagram
P52895
-, a drug acting as substrate
-
-
?
benzenedihydrodiol + NAD(P)+
? + NAD(P)+
show the reaction diagram
-
-
-
?
benzenedihydrodiol + NAD(P)+
? + NAD(P)+
show the reaction diagram
Rattus norvegicus, Rattus norvegicus Sprangue-Dawley
-
pH 9.0
-
?
benzo[c]phenanthrene-3,4-dihydrodiol + NADP+
? + NADPH + H+
show the reaction diagram
-
enzyme metabolizes both stereoisomers of benzo[c]phenanthrene-3,4-dihydrodiol
-
-
?
beta-muricholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
chenodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
cholic acid + NAD(P)+
3-oxocholate + NAD(P)H
show the reaction diagram
Eubacterium sp., Eubacterium sp. VPI 12708
-
-
very little activity
?
cholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
choloyl-CoA + NAD(P)+
3-oxocholoyl-CoA + NAD(P)H + H+
show the reaction diagram
Eubacterium sp., Eubacterium sp. VPI 12708
-
-
-
r
daunorubicin + NADPH
?
show the reaction diagram
P52895
-, a drug acting as substrate
-
-
?
dehydrolithocholic acid + NADH + H+
?
show the reaction diagram
-
-
-
-
?
deoxycholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
deoxycholoyl-CoA + NAD(P)+
3-oxodeoxycholoyl-CoA + NAD(P)H + H+
show the reaction diagram
Eubacterium sp., Eubacterium sp. VPI 12708
-
75% activity compared with cholyl-CoA
-
?
diacetyl + NADH
?
show the reaction diagram
-
-
-
-
?
dihydroprogesterone + NADPH
androsterone + NADP+
show the reaction diagram
-
-
-
-
?
dolasetron + NADPH
?
show the reaction diagram
P52895
-, a drug acting as substrate
-
-
?
etiocholane-3,17-dione + NADH
etiocholan-3alpha-ol-17-one + NAD+
show the reaction diagram
-
-
-
?
glycochenodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
glycochenodeoxycholic acid + NADP+
7alpha-hydroxy-3-oxo-5beta-cholanoyl glycine + NADPH
show the reaction diagram
-
-
-
?
glycolithocholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
glycolithocholic acid + NADP+
3-oxo-5beta-cholanoyl glycine + NADPH
show the reaction diagram
-
-
-
?
glycoursodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
haloperidol + NADPH
?
show the reaction diagram
P52895
-, a drug acting as substrate
-
-
?
hyodeoxycholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
isatin + NADH
?
show the reaction diagram
-
-
-
-
?
ketoprofen + NADPH
?
show the reaction diagram
P52895
-, a drug acting as substrate
-
-
?
ketotifen + NADPH
?
show the reaction diagram
P52895
-, a drug acting as substrate
-
-
?
lithocholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
lithocholic acid + NADP+
dehydrolithocholic acid + NADPH
show the reaction diagram
-
-
-
r
murocholic acid + NADH
?
show the reaction diagram
-
low activity
-
-
?
Naloxone + NADPH
?
show the reaction diagram
P52895
-, a drug acting as substrate
-
-
?
Naltrexone + NADPH
?
show the reaction diagram
P52895
-, a drug acting as substrate
-
-
?
oracin + NADPH
?
show the reaction diagram
P52895
-, a drug acting as substrate
-
-
?
oracin + NADPH
? + NADP+
show the reaction diagram
-
-
-
-
?
oxycodone + NADPH
?
show the reaction diagram
P52895
-, a drug acting as substrate
-
-
?
pregnane-11beta,17alpha,21-triol-3,20-dione + NADH
pregnane-3alpha,11beta,17alpha,21-tetrol-20-one + NAD+
show the reaction diagram
-
-
-
?
progesterone + NAD(P)H
3alpha-hydroxy-pregn-4-ene-20-one + NAD(P)+
show the reaction diagram
-
-
-
-
r
prostaglandin + NADP+
? + NADPH
show the reaction diagram
-
types A1, A2, B1, B2, D2, E1, E2, F1, F2alpha and 15-keto-prostaglandinE2 and F2alpha
-
-
prostaglandin-F2alpha + NADP+
prostaglandin F2 + prostaglandin B2 + NADPH
show the reaction diagram
-
-
-
?
taurolithocholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
tauroursodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
testosterone + NAD(P)H + H+
4-androsten-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
-
-
-
-
r
testosterone + NADH
?
show the reaction diagram
-
low activity
-
-
?
tibolone + NADPH
3-hydroxytibolone + NADP+
show the reaction diagram
-
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, i.e. [7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, stereoselctive reaction to the 3alpha-hydroxytibolone product
-
-
?
ursodeoxycholic acid + NADH
?
show the reaction diagram
-
-
-
-
?
loxoprofen + NADPH
?
show the reaction diagram
P52895
-, a drug acting as substrate
-
-
?
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
?
-
-
no activity with cholate, chenodeoxycholate, deoxycholate, glycocholate, taurocholate, ursodeoxycholate and bile acid
-
-
-
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
?
-
P23457
biosynthesis and inactivation of steroid hormones, physiological role is to inactivate circulating androgens, progestins and glucocorticoids
-
-
-
additional information
?
-
-
involved in biosynthesis of bile acids
-
-
-
additional information
?
-
-
inactivating circulating androgens, progestins and glucocorticoids. Regulation of hormone levels in endocrine target tissues and in carcinogen actibation
-
-
-
additional information
?
-
-
bifunctional enzyme exhibiting 3alpha-hydroxysteroid dehydrogenase activity and carbonyl reductase activity
-
-
-
additional information
?
-
-
an androgen-inactivating enzyme, important in androgen and progesterone metabolism
-
-
-
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
?
-
-
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
?
-
-
no activity with acetylpyrroles
-
-
-
additional information
?
-
-
the enzyme might play an important role in female physiology, substrate specificity, overview
-
-
-
additional information
?
-
-
AKR1C3 catalyzes androgen, estrogen, and prostaglandin metabolism, AKR1C3 is also involved in cancer development or progression
-
-
-
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
?
-
Eubacterium sp. VPI 12708
-
no activity with cholate, chenodeoxycholate, deoxycholate, glycocholate, taurocholate, ursodeoxycholate and bile acid
-
-
-
additional information
?
-
Rattus norvegicus Sprangue-Dawley
-
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, involved in biosynthesis of bile acids
-
-
-
additional information
?
-
Rattus norvegicus Sprangue-Dawley
-
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
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
10-oxonortriptyline + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
-
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
P23457
-
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
-
termination of androgen action
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
-
conversion in animal tissues
-
?
17beta-hydroxy-5alpha-androstan-3-one + NAD(P)H + H+
3alpha,17beta-dihydroxy-5alpha-androstan + NAD(P)+
show the reaction diagram
-
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)+
show the reaction diagram
Rattus norvegicus Sprangue-Dawley
-
termination of androgen action
-
?
2 tibolone + 2 NADPH + 2 H+
3alpha-hydroxytibolone + 3beta-hydroxytibolone + 2 NADP+
show the reaction diagram
-
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
3-ketosteroids + NADPH
3-hydroxysteroids + NADP+
show the reaction diagram
P52895
-
-
-
?
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
show the reaction diagram
-
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+
show the reaction diagram
-
steroid reduction direction is preferred
-
-
r
4-acetylpyridine + NADPH
(S)-1-(4-pyridyl)ethanol + NADP+
show the reaction diagram
-
-
-
-
?
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
show the reaction diagram
-
-
-
-
?
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
show the reaction diagram
-
inactivation of the potent androgen in human prostate
-
-
r
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
show the reaction diagram
-
inactivation of the potent androgen in human prostate, fluorometric activity measurement in intact cells, overview
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
-
-
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
P52895
androgen-inactivating enzyme
-
-
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
P52895
the enzyme is important in inactivation of DHT
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
show the reaction diagram
-
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 + H+
3alpha-androstanediol + NADP+
show the reaction diagram
-
steroid reduction direction is preferred
-
-
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnan-3alpha-ol-20-one + NAD(P)+
show the reaction diagram
-
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-tetraal-11-one + NAD(P)+
show the reaction diagram
-
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+
show the reaction diagram
-
competitive substrate, fluorometric activity measurement in intact cells, overview
-
-
?
acetohexamide + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
acetophenone + NADPH
1-phenylethanol + NADP+
show the reaction diagram
-
-
-
-
?
androsterone + NAD+
androstanedione + NADH
show the reaction diagram
-
-
-
-
r
androsterone + NAD+
5alpha-androstane-3,17-dione + NADH
show the reaction diagram
-
-
-
-
r
androsterone + NADP+
5alpha-androstane-3,17-dione + NADPH
show the reaction diagram
-
-
-
-
r
befunolol + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
daunorubicin + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
dolasetron + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
haloperidol + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
ketoprofen + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
ketotifen + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
Naloxone + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
Naltrexone + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
oracin + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
oxycodone + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
tibolone + NADPH
3-hydroxytibolone + NADP+
show the reaction diagram
-
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
-
-
?
loxoprofen + NADPH
?
show the reaction diagram
P52895
a drug acting as substrate
-
-
?
additional information
?
-
P23457
biosynthesis and inactivation of steroid hormones, physiological role is to inactivate circulating androgens, progestins and glucocorticoids
-
-
-
additional information
?
-
-
involved in biosynthesis of bile acids
-
-
-
additional information
?
-
-
inactivating circulating androgens, progestins and glucocorticoids. Regulation of hormone levels in endocrine target tissues and in carcinogen actibation
-
-
-
additional information
?
-
-
an androgen-inactivating enzyme, important in androgen and progesterone metabolism
-
-
-
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
?
-
-
AKR1C9 catalyzes androgen, estrogen, and prostaglandin metabolism
-
-
-
additional information
?
-
-
C/EBPdelta regulates the AKR1C9 gene promoter in osteoblasts, overview
-
-
-
additional information
?
-
Rattus norvegicus Sprangue-Dawley
-
involved in biosynthesis of bile acids
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
NAD(P)+
-
A-specific
NAD(P)H
-
A-specific
NAD(P)H
-
1000fold lower activity with NADH compared to NADPH
NAD(P)H
-
cofactor binding structure, overview
NAD+
-
higher activity
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
NADH
-
higher activity
NADH
-
A-specific
NADP+
-
A-specific
NADP+
-
lower activity
NADP+
-
A-specific
NADP+
-
cofactor binding site structure
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
-
lower activity
NADPH
-
preferred
NADPH
-
A-specific
NADPH
-
comparison of NADPH with deuterium-substituted NADPD, overview
NADPH
-
cofactor binding site structure
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
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
citrate
-
bound to the steroid-binding cavity via Tyr55 and His117, involved in the induced fit mechanism
additional information
-
non-metallo enzyme
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
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
(E/Z)-sulfindac
-
wild-type, W86Y and W227Y
1,10-phenanthroline
-
wild-type, W86Y and W227Y
1,7-phenanthroline
-
wild-type, W86Y and W227Y
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
2-[[(3-hydroxyphenyl)carbonyl]amino]-4,5-dimethoxybenzoic acid
-
-
2-[[(3-hydroxyphenyl)carbonyl]amino]-5-nitrobenzoic acid
-
-
21-hydroxypregn-4-ene-3,20-dione
-
-
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-hydroxyflavone
-
-
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
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
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'-hydroxyflavanone
-
-
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
5-bromo-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
-
-
5-chloro-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
-
-
5-hydroxyflavone
-
-
5beta-Pregnan-3beta-ol-20-one
-
-
6alpha-Methylprednisolone
-
-
7-hydroxyflavone
-
very potent inhibitor, 0.02 mM inhibits by 82.5%
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one
-
competitive
acetaminophen
-
non-competitive, only androsterone oxidation, pH 7.0
acetylenic ketones
-
inactivation by forming Michael adducts with enzyme nucleophiles
-
apigenin
-
0.02 mM inhibits by ca. 50%
arachidonic acid
-
-
aspirin
-
salicylate, non-competitive, only androsterone oxidation, pH 7.0
Betamethasone
-
non-competitive
celecoxib
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.050 mM in fluorometric assay, in vitro IC50: 0.050 mM in fluorometric assay
chlorogenic acid
-
-
Cibacron blue
-
nucleotide analog, competitive with respect to NADP+, noncompetitive to androsterone
cortisol
-
competitive
cortisone
-
competitive
Cu2+
-
100% inhibition at 0.1 mM
D-glucose 6-phosphate
-
-
dexamethasone
-
non-competitive
DMSO
-
33% inhibition
epigallocatechin gallate
-
-
Flufenamic acid
-
wild-type, W86Y and W227Y
Flufenamic acid
-
a nonsteroidalanti-inflammatory drug, IC50: 1.084 mM
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
-
competitive
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
-
-
Indomethacin
-
competitive, IC50 for reduction of 9,10-phenanthrenequinone is 0.000735 mM and of androsterone 0.00333 mM
Indomethacin
-
wild-type, W86Y and W227Y
iodoacetate
-
50% inhibition at 0.1 mM
isovitexin
-
-
Ketamine
-
specific inhibitor for AKR1C17, but no inhibition of AKR1C9
luteolin
-
0.02 mM inhibits by ca. 50%
Meclofenamic acid
-
competitive
Meclofenamic acid
-
wild-type, W86Y and W227Y
Medroxyprogesterone acetate
-
-
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
Naringenin
-
very potent inhibitor, 0.02 mM inhibits by 71.9%
non-steroidal anti-inflamatory drug
-
competitive
-
non-steroidal anti-inflamatory drug
-
-
-
Oxyphenybutazone
-
competitive
p-chloromercuribenzenesulfonate
-
-
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
non-competitive with respect to dihydrocortisone 46-100% inhibition at 0.01 mM, preincubation with NADH lowers the inhibitory effect
Phenolphthalein
-
AKR1C4-selective inhibitor, in vitro and in vivo inhibition, IC50: 0.0004 mM
Ponalrestat
-
wild-type, W86Y and W227Y, weak inhibitor
Prednisolone
-
competitive
Prednisone
-
competitive
progesterone
-
competitive to testosterone
Prostaglandin
-
A2alpha
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
Prostaglandin A1
-
-
prostaglandin A2alpha
-
-
Prostaglandin B1
-
-
prostaglandin E1
-
-
prostaglandin F1alpha
-
-
pyrazole
-
10% at 0.4 mM
quercetin
-
0.02 mM inhibits by ca. 50%
salicylate
-
non-competitive
silibinin
-
0.02 mM inhibits by ca. 50%
testosterone
-
competitive inhibitor of androsterone binding
testosterone
-
competitive to progesterone
Tolmetin
-
competitive, only androsterone oxidation, pH 7.0
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
Zomepirac
-
competitive, only androsterone oxidation, pH 7.0
zopolrestat
-
wild-type, W86Y and W227Y, weak inhibitor
Mefenamic acid
-
wild-type, W86Y and W227Y
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
-
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
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
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
-
bile acid-incucible baiA gene family
-
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
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0027
-
(5beta,20R)-20-hydroxypregnan-3-one
-
pH 7.4, 25C, 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
0.505
-
17beta-hydroxy-5alpha-androstan-3-one
-
NAD(H), prostate
0.614
-
17beta-hydroxy-5alpha-androstan-3-one
-
NADP(H), prostate
0.645
-
17beta-hydroxy-5alpha-androstan-3-one
-
NADP(H), epididymis
0.726
-
17beta-hydroxy-5alpha-androstan-3-one
-
NAD(H), epididymis
3.54
33.7
2-decalone
-
-
0.0031
-
3alpha-androstanediol
-
pH 7.0, 25C, recombinant enzyme
0.0013
0.0441
3alpha-hydroxy-5alpha-androstan-17-one
-
NAD+
0.0041
0.024
3alpha-hydroxy-5alpha-androstan-17-one
-
NADP+
0.0094
-
3alpha-hydroxy-5alpha-androstan-17-one
-
-
0.029
-
3alpha-hydroxy-5alpha-androstan-17-one
-
Y205F
0.042
0.408
3alpha-hydroxy-5alpha-androstan-17-one
-
-
0.046
-
3alpha-hydroxy-5alpha-androstan-17-one
-
recombinant wild type enzyme
0.047
-
3alpha-hydroxy-5alpha-androstan-17-one
-
-
0.163
0.211
4-nitrobenzyldehyde
-
-
-
0.0031
-
4-oxo-2-nonenal
-
pH 7.4, 25C
-
0.0011
0.0039
5alpha-Androstan-3,17-dione
-
NADPH
0.0017
-
5alpha-Androstan-3,17-dione
-
-
0.0039
0.0304
5alpha-Androstan-3,17-dione
-
NADH
0.0041
-
5alpha-Androstan-3,17-dione
-
recombinant wild type enzyme
0.0042
-
5alpha-Androstan-3,17-dione
-
Y205F
8e-05
-
5alpha-androstane-3,17-dione
-
-
0.00065
-
5alpha-androstane-3,17-dione
-
pH 7.0, 25, reduction reaction
0.781
-
5alpha-androstane-3alpha,17beta-diol
-
NAD(H), prostate
1.09
-
5alpha-androstane-3alpha,17beta-diol
-
NADP(H), prostate
3.042
-
5alpha-androstane-3alpha,17beta-diol
-
NAD(H), epididymis
7.331
-
5alpha-androstane-3alpha,17beta-diol
-
NADP(H), epididymis
0.0013
-
5alpha-dihydrotestosterone
-
recombinant enzyme in intact COS-1 cells
0.0029
-
5alpha-dihydrotestosterone
-
pH 7.0, 25C, recombinant enzyme
0.0057
-
5alpha-dihydrotestosterone
-
pH 7.5, recombinant wild-type enzyme
0.0059
-
5alpha-dihydrotestosterone
-
pH 7.5, recombinant mutant R301L
0.012
-
5alpha-dihydrotestosterone
-
pH 7.5, recombinant mutant R304L
0.0021
-
5beta-androstane-3,17-dione
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.01
-
5beta-pregnane-17alpha,20beta,21-triol-3,11-dione
-
-
0.0024
-
5beta-pregnane-3,20-dione
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.023
-
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.00122
0.0051
9,10-phenanthrenequinone
-
-
0.038
-
9,10-phenanthrenequinone
-
pH 7.4, 25C, 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
0.00044
-
androsterone
-
pH 9.0, 25C, recombinant mutant S114A/Y155F
0.0041
-
androsterone
-
pH 7.0, 25, oxidation reaction
0.0051
-
androsterone
-
pH 10.4, 25C, recombinant wild-type enzyme
0.0055
-
androsterone
-
pH 9.0, 25C, recombinant wild-type enzyme
0.007
-
androsterone
-
pH 9.0, 25C, recombinant mutant S114A
0.033
-
androsterone
-
pH 10.4, 25C, recombinant mutant K159A
0.065
-
androsterone
-
pH 9.0, 25C, recombinant mutant K159A
0.074
-
androsterone
-
pH 9.0, 25C, recombinant mutant Y155F
0.004
-
Dehydrolithocholic acid
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.42
-
Diacetyl
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.004
0.821
NAD+
-
-
0.83
-
NAD+
-
Y205F
0.94
-
NAD+
-
recombinant wild type enzyme
0.0057
0.0312
NADH
-
-
0.015
-
NADH
-
-
0.027
-
NADH
-
recombinant wild type enzyme
0.03
-
NADH
-
Y205F
0.033
-
NADH
-
-
0.0026
-
NADP+
-
-
0.0052
0.1515
NADP+
-
-
0.04
-
NADP+
-
-
0.00016
-
NADPH
-
-
0.0022
0.0081
NADPH
-
-
0.0001
-
Prostaglandin
-
-
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
0.1
-
androsterone
-
pH 9.0, 25C, recombinant mutant Y155F/K159A
additional information
-
benzo[a]pyrene-7,8-dihydrodiol
-
kcat/Km of 39 min/mM
0.022
-
isatin
-
pH 7.4, 25C, recombinant wild-type AKR1C17
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
-
kinetics
-
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
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.115
-
(5beta,20R)-20-hydroxypregnan-3-one
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.008
-
3alpha-androstanediol
-
pH 7.0, 25C, recombinant enzyme
1.13
-
3alpha-hydroxy-5alpha-androstan-17-one
-
Y205F
1.25
-
3alpha-hydroxy-5alpha-androstan-17-one
-
recombinant wild type enzyme
0.148
-
4-oxo-2-nonenal
-
pH 7.4, 25C
-
0.35
-
5alpha-androstan-17beta-ol-3-one
-
-
0.267
-
5alpha-Androstan-3,17-dione
-
Y205F
0.283
-
5alpha-Androstan-3,17-dione
-
recombinant wild type enzyme
0.567
-
5alpha-Androstan-3,17-dione
-
-
1.33
-
5alpha-androstan-3alpha,17beta-diol
-
-
2.72
-
5alpha-Androstan-3alpha-ol-17-one
-
-
0.42
-
5alpha-androstane-3,17-dione
-
pH 7.0, 25, reduction reaction
0.037
-
5alpha-dihydroprogesterone
-
cofactor NADPH, pH 7.0, 25C, steroid reduction, recombinant mutant W227A
0.3
-
5alpha-dihydroprogesterone
-
cofactor NADPH, pH 7.0, 25C, steroid reduction, recombinant wild-type enzyme
0.4
-
5alpha-dihydroprogesterone
-
cofactor NADPH, pH 7.0, 25C, steroid reduction, recombinant mutant R276M
0.43
-
5alpha-dihydroprogesterone
-
cofactor NADH, pH 7.0, 25C, steroid reduction, recombinant wild-type enzyme
0.033
-
5alpha-dihydrotestosterone
-
pH 7.0, 25C, recombinant enzyme
5.9
-
5alpha-dihydrotestosterone
-
pH 7.5, recombinant mutant R304L
22.1
-
5alpha-dihydrotestosterone
-
pH 7.5, recombinant mutant R301L
1339
-
5alpha-dihydrotestosterone
-
pH 7.5, recombinant wild-type enzyme
0.767
-
5alpha-pregnan-21-ol-3,20-one
-
-
0.233
-
5alpha-Pregnan-3alpha,21-diol-20-one
-
-
0.45
-
5beta-androstan-3,17-dione
-
-
1.2
-
5beta-Androstan-3alpha,17beta-diol
-
-
1.33
-
5beta-Androstan-3alpha-ol-17-one
-
-
0.047
-
5beta-androstane-3,17-dione
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.433
-
5beta-Dihydrocortisone
-
-
0.417
-
5beta-pregnan-3,20-dione
-
-
0.633
-
5beta-Pregnan-3alpha,21-diol-20-one
-
-
0.767
-
5beta-Pregnan-3alpha-ol-20-one
-
-
0.105
-
5beta-pregnane-3,20-dione
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.1
-
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.183
-
9,10-phenanthrenequinone
-
pH 7.4, 25C, recombinant wild-type AKR1C17
1.17
3.93
9,10-phenanthrenequinone
-
-
0.0028
-
androsterone
-
pH 9.0, 25C, recombinant mutant S114A/Y155F
0.003
-
androsterone
-
pH 9.0, 25C, recombinant mutant Y155F/K159A
0.0053
-
androsterone
-
steady-state, pH 8.0, 25C, recombinant mutant W227A
0.0083
-
androsterone
-
steady-state, pH 8.0, 25C, recombinant mutant F118A
0.12
-
androsterone
-
pH 9.0, 25C, recombinant mutant S114A
0.57
-
androsterone
-
steady-state, pH 8.0, 25C, recombinant mutant T226A
0.82
-
androsterone
-
pH 7.0, 25, oxidation reaction
0.83
-
androsterone
-
steady-state, pH 8.0, 25C, recombinant wild-type enzyme
1.5
-
androsterone
-
pH 9.0, 25C, recombinant mutant Y155F
18.9
-
androsterone
-
pH 9.0, 25C, recombinant mutant K159A
318
-
androsterone
-
pH 9.0, 25C, recombinant wild-type enzyme
0.022
-
Dehydrolithocholic acid
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.733
-
Dehydrolithocholic acid
-
-
0.167
-
Diacetyl
-
pH 7.4, 25C, recombinant wild-type AKR1C17
0.2
-
glycochenodeoxycholic acid
-
-
0.233
-
glycolithocholic acid
-
-
0.283
-
isatin
-
pH 7.4, 25C, recombinant wild-type AKR1C17
1.13
-
NAD+
-
recombinant wild type enzyme
1.43
-
NAD+
-
Y205F
0.283
-
NADH
-
recombinant wild type enzyme
0.367
-
NADH
-
Y205F
0.217
-
lithocholic acid
-
-
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
-
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
47.8
-
4-oxo-2-nonenal
-
pH 7.4, 25C
0
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
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
0.0022
-
4-androstene-3,17-dione
-
-
0.018
-
4-androstene-3,17-dione
-
-
0.0075
-
6alpha-Methylprednisolone
-
androsterone oxidation
0.006
-
arachidonic acid
-
-
0.006
-
arachidonic acid
-
androsterone oxidation
0.65
-
aspirin
-
for androsterone oxidation
0.0045
-
Betamethasone
-
androsterone oxidation
1e-05
-
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
0.19
-
cortisol
-
androsterone oxidation
0.285
-
cortisone
-
androsterone oxidation
0.01
-
dexamethasone
-
androsterone oxidation
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
0.00057
-
Indomethacin
-
-
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
0.017
-
NADH
-
-
0.0175
-
Prednisolone
-
androsterone oxidation
0.0175
-
Prednisone
-
androsterone oxidation
0.0031
-
Prostaglandin A1
-
androsterone oxidation
0.003
-
prostaglandin A2alpha
-
-
0.0008
-
Prostaglandin B1
-
androsterone oxidation
0.0075
-
prostaglandin E1
-
androsterone oxidation
0.012
-
prostaglandin F1alpha
-
androsterone oxidation
0.115
0.75
salicylate
-
-
0.001
-
Indomethacin
-
-
additional information
-
additional information
-
more Ki values given for different inhibitors of androsterone oxidation, 9,10-phenanthrenequinone- and 5alpha-androstane-3,17-dione reduction
-
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0136
-
(2E)-3-(4-bromophenyl)-2-[4-(methylsulfonyl)phenyl]prop-2-enoic acid
-
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
-
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
-
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
-
pH not specified in the publication, temperature not specified in the publication
9.4e-05
-
1-(4-[[(2R)-2-methylpiperidin-1-yl]sulfonyl]phenyl)-1,3-dihydro-2H-pyrrol-2-one
-
pH not specified in the publication, temperature not specified in the publication
5.6e-05
-
1-(4-[[(2R,6S)-2,6-dimethylpiperidin-1-yl]sulfonyl]phenyl)pyrrolidin-2-one
-
pH not specified in the publication, temperature not specified in the publication
5.2e-05
-
1-[4-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)phenyl]pyrrolidin-2-one
-
pH not specified in the publication, temperature not specified in the publication
0.0003
-
2'-hydroxyflavanone
-
-
0.000213
-
2-(2,4-dioxo-1,3-thiazolidin-5-yl)-N-(2-hydroxyphenyl)acetamide
-
pH 7.0, temperature not specified in the publication
0.0052
-
2-[[(3-hydroxyphenyl)carbonyl]amino]-4,5-dimethoxybenzoic acid
-
pH 7.0, temperature not specified in the publication
0.00084
-
2-[[(3-hydroxyphenyl)carbonyl]amino]-5-nitrobenzoic acid
-
pH 7.0, temperature not specified in the publication
0.08
-
3-((4-nitronaphthalen-1-yl)amino)benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
3.6e-05
-
3-[(4-nitrophenyl)amino]benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
5.4e-05
-
3-[[4-(methoxymethyl)phenyl]amino]benzoic acid
-
pH not specified in the publication, temperature not specified in the publication
6.2e-05
-
3-[[4-(trifluoromethyl)phenyl]amino]benzoic acid
-
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
-
pH 7.0, temperature not specified in the publication
0.0019
-
5-bromo-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
-
pH 7.0, temperature not specified in the publication
0.0022
-
5-chloro-2-[[(3-hydroxyphenyl)carbonyl]amino]benzoic acid
-
pH 7.0, temperature not specified in the publication
0.0049
-
7-hydroxyflavone
-
-
0.0218
-
apigenin
-
-
0.05
-
celecoxib
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.050 mM in fluorometric assay, in vitro IC50: 0.050 mM in fluorometric assay
0.00031
-
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
1.084
-
Flufenamic acid
-
a nonsteroidalanti-inflammatory drug, IC50: 1.084 mM
0.009
-
Ibuprofen
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.017 mM in fluorometric assay, in vitro IC50: 0.009 mM in fluorometric assay
0.000735
-
Indomethacin
-
competitive, IC50 for reduction of 9,10-phenanthrenequinone by NADPH at pH6.0 is 0.000735 mM
0.00333
-
Indomethacin
-
competitive, IC50 for oxidation of androsterone by NAD+ at pH 7.0 0.00333 mM
0.0374
-
luteolin
-
-
0.0027
-
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
0.0024
-
Naringenin
-
-
0.0004
-
Phenolphthalein
-
AKR1C4-selective inhibitor, in vitro and in vivo inhibition, IC50: 0.0004 mM
0.0188
-
quercetin
-
-
0.0062
-
silibinin
-
-
4.9e-05
-
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
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
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
0.006
-
-
purified recombinant mutant W227A, substrate androsterone
0.008
4
-
determined for several substrates,with best activities for 9,10-phenanthrenequinone, 4-nitrobezaldehyde and androsterone
0.01
-
-
purified recombinant mutant F118A, substrate androsterone
0.03
-
-
purified recombinant mutant F129A, substrate androsterone
0.059
-
-
W86Y mutant
0.07
-
-
recombinant AKR1C17 in cell extract, substrate 4-androsten-3alpha-ol-17-one
0.08
-
-
W227Y mutant
0.08
-
-
Q190A mutant, androsterone oxidation with NAD+
0.08
-
-
purified recombinant mutant L54A, substrate androsterone
0.09
-
-
purified recombinant mutant N306A, substrate androsterone
0.1
-
-
S166A mutant, androsterone oxidation with NAD+
0.1
-
-
purified recombinant mutant Y310A, substrate androsterone
0.23
-
-
purified recombinant AKR1C17, substrate 4-androsten-3alpha-ol-17-one
0.674
-
-
W148Y mutant
0.71
-
-
NADP+ dependent
0.81
-
-
Y216S mutant, androsterone oxidation with NADP+
0.86
-
-
purified recombinant mutant T24A, substrate androsterone
0.96
-
-
purified recombinant mutant T226A, substrate androsterone
1.5
-
-
native enzyme
1.55
-
-
recombinant wild type enzyme, androsterone oxidation with NAD+
1.6
-
-
purified recombinant wild-type enzyme, substrate androsterone
1.6
-
-
wild type homogeneous recombinant AKR1C9, at 25C
2
-
-
for androsterone
4.2
-
-
NAD+ dependent
6.2
-
-
testis
9.8
-
-
kidney
26.8
375
-
liver
9540
-
-
purified enzyme
additional information
-
-
enzyme contains conserved catalytic tetrad of Asp50, Tyr55, Lys84 and His117
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
-
-
assay at
7
-
-
bile acid determination assay at
7
-
-
assay at
7
-
-
assay at
7.4
9.5
-
recombinant enzyme
7.4
-
-
assay at
7.5
-
-
assay at
9
-
-
assay at
10.4
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
11
-
pH profile
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
assay at
25
-
-
assay at
25
-
-
assay at
25
-
-
assay at
25
-
-
assay at
25
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
the enzyme expression is positively correlated to adiposity in woman
Manually annotated by BRENDA team
-
high expression and activity in astrocytes of glaucomatous optic nerve head
Manually annotated by BRENDA team
-
the urothelial epithelium lining the renal pelvis is strongly immunoreactive, but stromal cells in the underlying supporting connective tissue are negative
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
only a small number of epithelial cells are immunoreactive with both nuclear and cytoplasmic reactivity
Manually annotated by BRENDA team
-
no activity in the stromal cells or endothelial cells, but weak immunoreactivity in the epididymal epithelial cells
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
-
strong isoform AKR1C3 immunoreactivity in columnar epithelium but only weak immunoreactivity in squamous epithelium of the gastrointestinal junction
Manually annotated by BRENDA team
-
primary, high expression and activity in healthy hepatocytes
Manually annotated by BRENDA team
-
specific expression of AKR1C17, two enzymes are expressed more highly in renal cortex than in the medulla
Manually annotated by BRENDA team
-
in renal cortex, endothelial cells of the glomeruli lack immunoreactivity for AKR1C3, but the Bowmans capsule and mesangial cells are strongly reactive, as well as larger epithelial cells of the medulla, overview
Manually annotated by BRENDA team
-
also present in kidney and testis
Manually annotated by BRENDA team
-
isozyme AKR1C9
Manually annotated by BRENDA team
-
high expression and activity in female and male liver
Manually annotated by BRENDA team
-
same expression level in female and male livers
Manually annotated by BRENDA team
Rattus norvegicus Sprangue-Dawley
-
-
-
Manually annotated by BRENDA team
-
strong isoform AKR1C3 immunoreactivity in bronchial epithelium but not in bronchial glands or alveolar pneumocytes
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
-
6fold higher expression level in female than in male pituitary
Manually annotated by BRENDA team
P52895
in primary prostate stromal cells, co-localization with RODH like 3alpha/17beta-HSD, EC 1.1.1.239
Manually annotated by BRENDA team
-
epithelial cells, but not the stromal cells or endothelial cells
Manually annotated by BRENDA team
-
lumbar, of naive, sham-operated and neuropathic rats, enzyme expression analysis and cellular distribution in neurons and glial cells, immunohistochemic analysis, overview
Manually annotated by BRENDA team
-
abundant enzyme expression
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
-
in Leydig cells, but no or poor activity in germ cells and Sertoli cells
Manually annotated by BRENDA team
-
positive AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction
Manually annotated by BRENDA team
additional information
-
indomethacin-sensitive 3alpha-hydroxysteroid dehydrogenase widely distributed in prostate, spleen, heart, testis, small intestine, stomach, lung and brain
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
additional information
-
wide tissue distribution
Manually annotated by BRENDA team
additional information
-
no activity in the hepatoma cell line Hep-G2
Manually annotated by BRENDA team
additional information
-
the androgen-inactivating enzyme is selectively expressed in female tissue, while it is mostly absent in male tissue, tissue distribution, overview
Manually annotated by BRENDA team
additional information
-
tissue distribution of isozymes, overview
Manually annotated by BRENDA team
additional information
-
tissue distribution of AKR1C3, immunohistochemic analysis, overview
Manually annotated by BRENDA team
additional information
-
tissue distribution of AKR1C9, immunohistochemic analysis, overview
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
additional information
Rattus norvegicus Sprangue-Dawley
-
indomethacin-sensitive 3alpha-hydroxysteroid dehydrogenase widely distributed in prostate, spleen, heart, testis, small intestine, stomach, lung and brain
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
expression of AKR1C17 and AKR1C9
Manually annotated by BRENDA team
Rattus norvegicus Sprangue-Dawley
-
;
-
Manually annotated by BRENDA team
additional information
-
subcellular localization study, overview
-
Manually annotated by BRENDA team
additional information
-
subcellular localization of isozymes, overview
-
Manually annotated by BRENDA team
additional information
-
tissue-dependent subcellular localization, overview
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
27000
-
-
PAGE, western blot
34600
-
-
gel filtration
35000
-
-
gel filtration
36000
-
-
recombinant AKR1C17, gel filtration
37030
-
-
predicted molecular weight from the cDNA
74000
75000
-
native PAGE, kidney enzyme
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 32000, about, recombinant His-tagged wild-type and mutant enzymes, SDS-PAGE
?
-
x * 37000, SDS-PAGE
?
-
x * 33000, SDS-PAGE
dimer
-
2 * 26000
dimer
-
asymmetric heterodimer, crystal structure analysis
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
dimer
-
2 * 26000
-
monomer
-
1 * 35000 SDS-PAGE
monomer
-
1 * 34000 SDS-PAGE
monomer
-
1 * 33000 gel filtration; 1 * 34000 SDS-PAGE
monomer
-
1 * 37029
monomer
-
1 * 37000, SDS-PAGE
monomer
-
1 * 33500, SDS-PAGE
monomer
-
1 * 37000, recombinant AKR1C17, SDS-PAGE
tetramer
-
-
tetramer
Eubacterium sp. VPI 12708
-
-
-
monomer
Rattus norvegicus Sprangue-Dawley
-
1 * 33000 gel filtration; 1 * 34000 SDS-PAGE; 1 * 34000 SDS-PAGE
-
additional information
-
(alpha/beta)8-barrel fold
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
-
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
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
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, 4C, 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
-
purified enzyme with NADH, hanging drop vapour diffusion method, 4C, 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
-
vapor diffusion techniques using ammonium sulfate as precipitant
-
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
45
-
-
50% inactivation after 17 min
45
-
-
inactivated in absence of ligand, protected only by the addition of NADP+
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
4C, 10 mM-Tris/HCl, pH 8.0, 5 mM 2-mercaptoethanol, 0.5 mM EDTA, 20% glycerol
-
-10C, 3 weeks, activity declines about 50%
-
-10C, most purified preparation, 5 days, loses between 80% and 100% of activity
-
-70C, 20 mM potassium phosphate buffer, pH 7.0, 1 mM EDTA, 1 mM beta-mercaptoethanol, 30% glycerol
-
-80C, 20 mM potassium phosphate buffer, pH 7.0, 1 mM EDTA, 1 mM DTT, 30% glycerol
-
3C, first ammonium sulfate fraction, stable at least 3 weeks
-
3C, most purified preparation, 5 days, loses 50% of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain Bl21(DE3) by nickel affinity chromatography, to homogeneity
-
recombinant wild-type and mutant enzymes ifrom Escherichia coli strain BL21(DE3)
-
Centriprep-10 concentration, DEAE-HPLC
-
recombinant enzyme from Escherichia coli strain C41(DE3) in a successive chromatographic procedure, to homogeneity
-
recombinant GST-fusion wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by glutathione affinity and anion exchange chromatography, and gel filtration to homogeneity
-
ammonium sulfate precipitation, Q-Sepharose, Red A, HA-Ultrogel, Sephadex G-100, copurification with NAD+ dependent enzyme
-
ammonium sulfate precipitation, Ca2(PO4)2 gel extraction, ethanol precipitation
-
anion exchange and Blue Sepharose column
-
anion exchange and Blue Sepharose column; N167A chromatofocusing and gel filtration introduced between the to others chromatography steps
-
CaCl2 and ammonium sulfate fractionation, DEAE-cellulose- and hydroxyapatite chromatography, chromatofocusing, Sephadex G-100
-
native enzyme 73.3fold from liver by ammonium sulfate, anion-exchange chromatography, gel filtration, and affinity chromatography
-
purification of recombinant wild type and mutants of AKR1C9
-
recombinant wild-type and mutant AKR1C17s from Escherichia coli strain BL21(DE3)
-
recombinant wild-type and mutant enzymes from Escherichia coli C41(DE3), to homogeneity
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression of His-tagged wild-type and mutant enzymes in Escherichia coli
-
expression of wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
overexpression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
overexpressed in Escherichia coli HMS174(DE3)
-
AKR1C3 PCR fragment cloned into pCR2.1-TOPO and then into vector pET15b and overexpressed in Escherichia coli strain BL21(DE3)
-
chromosomal localization is 10q15-q14, phylogenetic tree
-
expression in Cos-1 cells
-
expression in Escherichia coli
-
overexpression in Escherichia coli strain C41(DE3)
-
overexpression of GST-fusion wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)
-
transient functional expression in PC3 and COS-1 cells, trans-activation of the enzyme using a CAT reporter gene assay, overview
P52895
DNA and amino acid sequence analysis and comparison
-
expression and promoter activity analysis, genetic enzyme regulation, overview
-
expression of recombinant wild type and mutants of AKR1C9
-
expression of wild-type and mutant AKR1C17s in Escherichia coli strain BL21(DE3)
-
full-length cDNA gene is expressed in Escherichia coli DH5alpha
-
overexpression of AKR1C9 in Escherichia coli
-
overexpression of wild-type and mutant enzymes in Escherichia coli C41(DE3)
-
plasmid DNA containing cDNA is transformed in Escherichia coli HB101, cDNA is used for sequencing
-
stable expression of wild-type and mutant enzymes in HEK-293 cells
-
wild-type enzyme and mutants are overexpressed in Escherichia coli DH5alpha
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
the expression of isoform AKR1C3 is reduced in both hyperplastic and carcinomatous endometrial epithelium
-
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
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
K159A
-
site-directed mutagenesis, altered kinetics in comparison to the wild-type enzyme
K159A
-
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
R301L
-
site-directed mutagenesis, the mutation greatly affects the 3alpha-hydroxysteroid dehydrogenase activity towards 5alpha-dihydrotestosterone and almost completely abolishes the 17beta-hydroxysteroid dehydrogenase activity of the enzyme
R304L
-
site-directed mutagenesis, the mutation greatly affects the 3alpha-hydroxysteroid dehydrogenase activity towards 5alpha-dihydrotestosterone and abolishes the 17beta-hydroxysteroid dehydrogenase activity of the enzyme
C217A
-
resistant to inactivation by secosteroids, therefore Cys217 is the point of covalent attachment of acetylenic ketones
D50E
-
1/30th catalytic efficiency of wild type, unlikely to be the general amino acid for catalysis
D50N
-
1/30th catalytic efficiency of wild type, unlikely to be the general amino acid for catalysis
E276R
-
site-directed mutagenesis, the mutation alters the cofactor specificity of AKR1C17 from NAD+ to NADP+, the switch is analogy th the residues of AKRc9 and its cofactor specificity, overview
F118A
-
site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
F118A
-
largest changes in kcat/Km
F129A
-
site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
F129A
-
largest changes in kcat/Km, F129A alters the stereochemical preference from oxidizing predominantly the S,S-stereoisomer to oxidizing predominantly the R,R-stereoisomer of benzo[g]chrysene-11,12-dihydrodiol
H117A
-
1/500th catalytic efficiency of wild type, unlikely to be the general amino acid for catalysis
K84M
-
inactive, unable to bind steroids
K84R
-
inactive, unable to bind steroids
L54A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
N167A
-
site-directed mutagenesis, most impaired enzyme
N306A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
N306A
-
mutant shows intermediate changes in kcat/Km versus wild type
Q190A
-
site-directed mutagenesis, decreased binding affinity to NADP(H), only binding of cofactor is affected, residue is located at the catalytic cente
Q270K
-
site-directed mutagenesis, the mutation alters the cofactor specificity of AKR1C17 from NAD+ to NADP+, the switch is analogy th the residues of AKRc9 and its cofactor specificity, overview
Q270K/E276R
-
site-directed mutagenesis, the mutation alters the cofactor specificity of AKR1C17 from NAD+ to NADP+, the switch is analogy th the residues of AKRc9 and its cofactor specificity, overview
R276E
-
site-directed mutagenesis, the mutant shows increased preference for the oxidation reaction compared to the wild-type enzyme
R276G
-
site-directed mutagenesis, the mutant shows slightly increased preference for the reduction reaction compared to the wild-type enzyme
R276M
-
elimination of salt bridge between Arg276 and the 2'-phosphate of AMP results in 100fold decrease of the affinity to NADP(H)
R276M
-
site-directed mutagenesis, mutant does no longer form a salt-linkage to the phosphate of 2'-AMP, and does no longer bind tightly to NAD(P)H, the burst phase kinetics for the NADP+-dependent oxidation of 3alpha-diol is eliminated
R276M
-
site-directed mutagenesis, the mutant shows slightly increased preference for the reduction reaction compared to the wild-type enzyme
S166A
-
site-directed mutagenesis, decreased binding affinity to NADP(H), only binding of cofactor is affected, residue is located at the catalytic center
T226A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
T226A
-
smallest change in kcat/Km is observed when alanine is used to substitute hydrophilic residues
T24A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
T24A
-
smallest change in kcat/Km is observed when alanine is used to substitute hydrophilic residues
W148Y
-
site-directed mutagenesis, kinetically similar to wild type enzyme, no function in ligand binding
W148Y
-
can catalyse steroid oxidoreduction similar to wild type, plays no role in steroid binding or catalysis
W227A
-
site-directed mutagenesis, highly reduced activity compared to the wild-type, very slow chemical transformation
W227A
-
site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme, 23fold decreased affinity for progesterone, effects of mutation on binding constants and kinetics, overview
W227A
-
largest changes in kcat/Km
W227Y
-
site-directed mutagenesis, important role in binding steroid hormones, but not small substrates or inhibitors, interacts with the C and/or D-rings of steroid ligand
W227Y
-
mainly influenced in steroid binding
W86Y
-
site-directed mutagenesis, important in binding steroids and non-steroidal anti-inflamatory drugs, region in which it resides is part of the substrate/inhibitor binding pocket, near the A-, and B-rings of bound steroid
W86Y
-
plays role in cofactor and steroid binding
Y205F
-
kinetically indistinguishable from the wild type, no general amino acid for catalysis in 3alpha-hydroxysteroid dehydrogenase
Y216S
-
site-directed mutagenesis, decreased binding affinity to NADP(H), only binding of cofactor is affected, residue is located at the catalytic cente
Y310A
-
site-directed mutagenesis, reduced activity compared to the wild-type enzyme, effects of mutation on binding constants and kinetics, overview
Y310A
-
mutant shows intermediate changes in kcat/Km versus wild type
Y55F
-
inactive, unable to perform steroid oxidoreduction, strongest candidate for the general amino acid
Y55S
-
inactive, strongest candidate for the general amino acid
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
additional information
-
co-immobilization of the enzyme with diaphorase of Clostridum sp. onto alkylamine glass beads through glutaraldehyde coupling for determination of bile acids, method opimization and evaluation, loss of 30% of activity after 4 months of regular use, overview
additional information
-
construction of insertion mutants, overview
Y155F/K159A
-
site-directed mutagenesis, altered kinetics in comparison to the wild-type enzyme
additional information
-
potential CoA binding sites spanning residues 182 to 193. N-terminal region is thought to contain the NAD(P)+ binding site, the middle and C-terminal regions the active site of the enzyme
additional information
Eubacterium sp. VPI 12708
-
potential CoA binding sites spanning residues 182 to 193. N-terminal region is thought to contain the NAD(P)+ binding site, the middle and C-terminal regions the active site of the enzyme
-
L54A
-
mutant shows intermediate changes in kcat/Km versus wild type
additional information
-
positions of Tyr/Lys pair are conserved across the aldo-keto reductase and short-chain dehydrogenase/reductase family. Tyr retains ability to form ternary complex and acts as general acid
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
diagnostics
-
co-immobilization of the enzyme with diaphorase of Clostridum sp. onto alkylamine glass beads through glutaraldehyde coupling for determination of bile acids in serum and bile in a cost-effective colorimetric assay
synthesis
-
the enzyme is useful in 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
drug development
-
2'-hydroxyflavanone may be useful for clinical therapy of malignancies where AKR1C3 is overexpressed like in prostate and breast cancer
medicine
-
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. Pretreatment of the resistant cells with proteasome inhibitor Z-Leu-Leu-Leu-al augments the cisplatin sensitization elicited by aldo-keto reductase inhibitors
medicine
-
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
medicine
-
positive isoform AKR1C3 immunoreactivity is extensively present in both adenocarcinoma and squamous cell carcinoma arising from the lung and the gastroesophageal junction. Isoform AKR1C3 immunoreactivity is absent in small cell carcinoma of the lung
drug development
-
the enzyme is a target for treatment of chronic pain in neuropathic diseases, overview