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Enzyme Nomenclature
Information on EC 1.1.1.50 - 3alpha-hydroxysteroid 3-dehydrogenase (Si-specific)
Word Map on EC 1.1.1.50
- 1.1.1.50
-
aldo-keto
-
androgen
- testosterone
-
reductases
-
beta-hydroxysteroids
-
alpha-reductase
- dihydrotestosterone
- androsterone
- dihydrodiol
- indomethacin
-
beta-diol
- 3alpha-hydroxysteroids
-
hydroxysteroids
-
alpha-dihydrotestosterone
-
alpha-androstane-3
- 17beta-hsd
-
alpha-diol
-
chenodeoxycholic
- 3-ketosteroids
-
alpha-hsdh
-
alpha-androstanediol
-
alpha-hydroxy-5
- chlordecone
- akr1d1
-
20-ketosteroid
-
alpha,17
-
trans-dihydrodiols
- ketosteroid
-
alpha-reduced
-
lithocholic
-
talalay
- 9,10-phenanthrenequinone
- 20alpha-hsd
-
pre-receptor
- 15-hydroxyprostaglandin
-
beta-reductase
-
alpha-dht
- environmental protection
- drug development
- synthesis
- biotechnology
- analysis
- medicine
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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
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EC NUMBER 
COMMENTARY 
1.1.1.50
-
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RECOMMENDED NAME
GeneOntology No.
3alpha-hydroxysteroid 3-dehydrogenase (Si-specific)
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
enzyme isoforms bind substrate in different ways
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
; reaction mechanism: ordered bi bi with random substrate binding and ordered release of product, NADPH is released last, pro-R-hydrogen atom of NAD(P)H is transferred to carbonyl substrate
-
-
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
ordered bi bi kinetic reaction mechanism with nucleotide cofactor binding first
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
reaction mechanism
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
isozymes AKR1C1 and AKR1C2 are bifunctional enzymes also showing minor 20alpha-hydroxysteroid dehydrogenase activity, EC 1.1.1.149
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
steroid binding pocket structure of isozyme AKR1C2
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
steroid binding pocket structure of isozyme AKR1C9
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
ordered bi bi kinetic mechanism, catalytic residues are Y55 and H117
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
isozymes also performs 17- and 20-ketosteroid reductase and 3alpha-, 17beta- and 20alpha-hydroxysteroid oxidase activities at varying rates
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
steroid substrate recognition mechanism by isozymes AKR1C1-AKR1C4, Tyr55 is involved in catalysis, ordered bi bi mechanism
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
the catalytic triad is composed of Ser-114, Tyr-155, and Lys-159, structural analysis and sequence alignment of the short chain dehydrogenase/reductase family
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
the reduction reaction is slightly preferred by the wild-type enzyme, which is determined by residue Arg276
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
the enzyme shows a sequential ordered reaction mechanism, where NAD+ binds to the enzyme first and NADH leaves last
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
bi bi ordered mechanism, kinetic analysis, overview
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
The overall oxidoreductive reaction comprises the deprotonation of tyrosine, proton abstraction by the tyrosinate anion, and hydride transfer from the hydroxysteroid to NAD+, followed by the release of a proton from the hydroxy group of tyrosine to the solution. The proton transfer to the external base, from Tyr155 to Lys159 via 2'-OH of ribose, with a late transition state is the rate-limiting step, mechanism, overview
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
rate-limiting step in the reaction is the release of NADH and proton. P185, T188 and the flexible substrate-binding loop are involved in binding with the nucleotide cofactor and with androsterone and are also involved in catalysis, catalytic mechanism, overview
-
a 3alpha-hydroxysteroid + NAD(P)+ = a 3-oxosteroid + NAD(P)H + H+
ordered bi bi kinetic reaction mechanism with nucleotide cofactor binding first
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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SYSTEMATIC NAME
IUBMB Comments
3alpha-hydroxysteroid:NAD(P)+ 3-oxidoreductase (Si-specific)
The enzyme acts on androsterone and other 3alpha-hydroxysteroids and on 9-, 11- and 15-hydroxyprostaglandin. Si-specific with respect to NAD+ or NADP+. cf. EC 1.1.1.213, 3alpha-hydroxysteroid 3-dehydrogenase (Re-specific).
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CAS REGISTRY NUMBER
COMMENTARY
9028-56-2
-
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
-
UniProt
floxglove, NADH-linked 5beta-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity
-
-
-
-
-
-
349245, 389525, 389526, 389528, 389530, 389531, 389532, 389540, 389544, 389554, 389556, 655790, 673349, 685529, 687635, 689169
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-
NADPH- and NADH-linked 5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity
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-
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
physiological function
additional information
evolution
human 3alpha-HSD3 shares 97.8% sequence identity with human 20-alpha hydroxysteroid dehydrogenase (20alpha-HSD) and there is only one amino acid difference (residue 54) that is located in their steroid binding pockets. 20alpha-HSD displays a distinctive ability in transforming progesterone to 20alpha-hydroxy-progesterone
evolution
-
enzyme 3alpha-HSD/CR belongs to the short chain dehydrogenase/reductase (SDR) superfamily
malfunction
the V54L mutation significantly decreases the 3alpha-HSD activity for the reduction of 5alpha-dihydrotestosterone, while this mutation enhances the 20alpha-HSD activity to convert progesterone
malfunction
enzyme silencing by specific siRNA suppresses 3alpha-HSD3 expression without interfering with 3alpha-HSD4, which shares a highly homologous active site, the 5alpha-DHT concentration increases, whereas MCF-7 cell growth is suppressed. Downregulation of 3alpha-HSD3 decreases MCF-7 breast cancer cell growth
malfunction
-
mutation at P185 in the hinge region and T188 in the loop causes a significant increase in the Kd value for NADH. Mutants P185A, P185G, T188A, and T188S show an increase the dissociation of the nucleotide cofactor, thereby increasing the rate of release of the product and producing the rate-limiting step in the hydride transfer
physiological function
-
replacement of hsdA gene by the green fluorescent protein gene inserted downstream from the hsdA regulatory region and use of the resulting strain as fluorescence based biosensor system for steroid determination. With this cell-based system testosterone can be determined in a range between 57 and 450 ng/ml, estradiol between 1.6 and 12.8 ng/ml, and cholesterol between 19.3 and 154.4 ng/nl. The sensitivity of this bioassay can be further increased by using only the cytosol of the mutant. With the resulting cell-free system testosterone is determined in a range between 28 and 219 pg/ml, estradiol between 0.029 and 0.430 fg/ml, and cholesterol between 9.7 and 77.2 fg/ml. The recovery ratio of the extraction is around 95% and the maximum fluorescence signals are obtained as early as after 30 min. Limitations of the established steroid biosensor system are quenching at higher steroid concentrations and the relatively high background of fluorescence
physiological function
3-alpha hydroxysteroid dehydrogenase type 3 has an essential role in the inactivation of 5alpha-dihydrotestosterone preventing binding and activation of androgen receptor from overflowing androgen
physiological function
3alpha-hydroxysteroid dehydrogenase type 3 plays an essential role in the inactivation of the most potent androgen 5alpha-dihydrotestosterone. Role of 3alpha-HSD3 in breast cancer cells
physiological function
3alpha-hydroxysteroid dehydrogenase catalyzes the oxidation of the 3-hydroxyl group of steroids. The enzymatic conversion is a critical step in the enzymatic assay of urinary sulfated bile acids
additional information
effect of progesterone in lesions, caused by neurotoxic 6-hydroxydopamine hydrobromide, on the contralateral turning behavior, overview
additional information
-
catalytic tetrad N86-S114-Y155-K159, catalytic roles of P185 and T188 and substrate-binding loop flexibility in 3alpha-hydroxysteroid dehydrogenase/carbonyl reductase. Structurally the substrate-binding loop of the residues, T188-K208, is unresolved, while binding with NAD+ causes the appearance of T188-P191 in the binary complex, functional roles of the flexible substrate-binding loop in conformational changes and enzyme catalysis, overview. Simulated molecular modeling gives results that are consistent with the conformational change in the substrate-binding loop after NAD+ binding. These results indicate that P185, T188 and the flexible substrate-binding loop are involved in binding with the nucleotide cofactor and with androsterone and are also involved in catalysis. Homology structure modeling, overview
additional information
-
effect of progesterone in lesions, caused by neurotoxic 6-hydroxydopamine hydrobromide, on the contralateral turning behavior, overview
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
17beta-hydroxy-dihydrotestosterone + NAD+
5alpha-androstan-3,17-dione + NADH
-
-
-
r
3-oxocholic acid + NADPH
3alpha-hydroxycholic acid + NADP+
-
reverse reaction rate negligible
-
ir
3alpha,12alpha-dihydroxy-5beta-cholanoyl glycine + NAD+
12alpha-hydroxy-3-oxo-5beta-cholanoyl glycine + NADH
-
-
-
-
?
3alpha,17alpha,21-trihydroxy-5beta-pregnan-11,20-dione + NADP+
17alpha,21-dihydroxy-5beta-pregnan-3,11,20-trione + NADPH
-
-
-
r
3alpha,17beta-androstene-3,17-diol + NAD(P)+
dihydrotestosterone + NAD(P)H + H+
-
-
-
?
3alpha,21-dihydroxy-5beta-pregnan-20-one + NADP+
21-hydroxy-5beta-pregnan-3,20-dione + NADPH
-
-
-
-
r
3alpha,5alpha, 20alpha-trihydroxyprogesterone + NADP+
5alpha, 20alphy-dihydroxyprogesterone-3-one + NADPH
-
-
-
-
r
3alpha,7alpha,12alpha-trihydroxy-5beta-cholanoyl glycine + NAD+
7alpha,12alpha-dihydroxy-5beta-cholan-3-one-24-oyl glycine + NADH
3alpha,7alpha-dihydroxy-5beta-cholanoyl glycine + NAD+
7alpha-hydroxy-3-oxo-5beta-cholanoyl glycine + NADH
-
-
-
-
?
3alpha-androstanediol + NAD+
5alpha-dihydrotestosterone + NADH
-
oxidation utilizing NAD+ as a cofactor is the preferred reaction in vitro
-
-
r
3alpha-hydroxy-12-oxo-9,11-cholenic acid + NADP+
3,12-dioxo-9,11-cholenic acid + NADPH
-
-
-
-
?
3alpha-hydroxy-5alpha-pregnan-20-one + NADP+
5alpha-pregnan-3,20-dione + NADPH
-
-
-
-
?
3alpha-hydroxy-5alpha-pregnan-20-one + NADP+
5alpha-pregnan-3,20-dione + NADPH + H+
-
-
-
-
r
3alpha-hydroxypregn-4-en-20-one + NADP+
pregn-4-en-3,20-dione + NADPH + H+
-
-
-
-
?
3alpha-hydroxytibolone + NAD+
tibolone + NADH
-
isozymes AKR1C2 and AKR1C4, no activity with isozyme AKR1C1
-
-
r
3alpha-tetrahydroprogesterone + NADH
5alpha-dihydroprogesterone + NAD+
-
-
-
r
3beta-hydroxytibolone + NAD+
tibolone + NADH
-
isozymes AKR1C2, AKR1C1, and AKR1C4
-
-
r
4'-methoxyacetophenone + NADPH + H+
1-(4-methoxyphenyl)ethanol + NADP+
-
-
R,S-enantiomeric product
-
?
4-androsten-3alpha-ol-17-one + NADH + H+
4-androsten-3alpha,17beta-diol + NAD+
-
AKR1C17
-
-
r
4-androstene-3,17-dione + NADH + H+
4-androsten-3alpha-ol-17-one + NAD+
-
low activity
-
-
r
4-bromoacetophenone + NADPH + H+
1-(4-bromophenyl)ethanol + NADP+
-
-
-
-
?
4-cyanoacetophenone + NADPH + H+
1-(4-cyanophenyl)ethanol + NADP+
-
-
-
-
?
4-methylacetophenone + NADPH + H+
1-(4-methylphenyl)ethanol + NADP+
-
-
R,S-enantiomeric product
-
?
4-pregnen-3alpha,20beta-diol + NAD+
(20beta)-20-hydroxypregn-4-en-3-one + NADH + H+
-
-
-
?, ir
5alpha-androstan-3,17-dione + NADPH + H+
3alpha-hydroxy-5alpha-androstan-17-one + NADP+
-
-
-
r
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
17beta-hydroxy-5alpha-androstan-3-one + NADPH
5alpha-androstan-3alpha-ol-17-one + NADH + H+
5beta-androstan-3alpha,17beta-diol + NAD+
-
-
-
-
r
5alpha-androstane-3,17-dione + NADH
5alpha-androstan-3alpha-ol-17-one + NAD+
-
low activity
AKR1C9
-
r
5alpha-androstane-3,17-dione + NADH + H+
androsterone + NAD+
-
-
-
-
?
5alpha-dihydrocortisol + NADPH
3alpha,5alpha-tetrahydrocortisol + NADP+
-
-
-
?
5alpha-dihydroprogesterone + NAD(P)H
4-pregnen-3alpha,20beta-diol + NAD(P)+
-
-
-
-
?
5alpha-dihydroprogesterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
isozymes AKR1C1-AKR1C4
-
-
r
5alpha-dihydroprogesterone + NADPH
5alpha-hydroxy-pregnan-20-one + NADP+
-
isozyme AKR1C2
-
-
?
5alpha-dihydroprogesterone + NADPH + H*
3alpha,5alpha-3-hydroxypregnan-20-one + 5alpha,20alpha-tetrahydroprogesterone + NADP+
-
-
-
-
?
5alpha-dihydrotestosterone + NADH
3alpha-androstanediol + NAD+
-
reaction direction is regulated by the NAD+:NADPH relation in the cell
-
-
r
5alpha-pregnane-20alpha-ol-3-one + NADH
5alpha-pregnane-3,20alpha-diol + NAD+
-
-
-
-
?
5alpha-pregnane-3,20-dione + NADH
5alpha-pregnan-3alpha-ol-20-one + NAD+
-
low activity
-
-
r
5beta-androstan-3,17-dione + NADPH
5beta-androstan-3alpha,17alpha-diol + NADP+
-
-
-
r
5beta-androstan-3alpha-ol-17-one + NADH
5beta-androstane-3alpha,17beta-diol + NAD+
-
-
-
-
r
5beta-androstan-3alpha-ol-17-one + NADPH
5beta-androstan-3alpha,17alpha-diol + NADP+
-
-
-
r
5beta-androstane-3,17-dione + NADH
5beta-androstan-3alpha-ol-17-one + NAD+
-
-
-
-
r
5beta-androstane-3,17-dione + NADH + H+
5beta-androstan-3alpha-ol-17-one + NAD+
-
-
-
-
?
5beta-dihydrocortisol + NADPH
3alpha,5beta-tetrahydrocortisol + NADP+
-
-
-
?
5beta-dihydroprogesterone + NADPH + H+
3alpha,5beta-3-hydroxypregnan-20-one + NADP+
-
preferred substrate
-
-
?
5beta-pregnane-20alpha-ol-3-one + NADH + H+
5beta-pregnane-3,20alpha-diol + NAD+
-
-
-
-
?
5beta-pregnane-3,20-dione + NADH + H+
5beta-pregnan-3alpha-ol-20-one + NAD+
-
-
-
-
r
6-ketolithocholate + NAD+
5beta-cholan-3,6-dione-24-oic acid + NADH
-
-
-
-
r
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one + NADH
?
-
the enzyme produces both R- and S-form products in a ratio of 2.3 : 1
-
-
?
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+
androsterone + NAD+
5alpha-androstane-3,17-dione + NADH + H+
-
-
-
-
?
chenodeoxycholic acid + NAD+
7alpha,12alpha-dihydroxy-5beta-cholan-3-one-24-oic acid + NADH
cholate + NAD+
7alpha,12alpha-dihydroxy-3-oxo-5beta-cholan-24-oic acid + NADH + H+
-
-
-
r
cholic acid + thio-NAD+
7alpha,12alpha-dihydroxy-5beta-cholan-3-one-24-oic acid + thio-NADH
-
-
-
-
?
etiocholan-3alpha-ol-17-one + NADP+
etiocholan-3,17-dione + NADPH
-
-
-
-
?
fusidic acid + NAD+
3-oxofusidic acid + NADH
-
antibiotic steroid substrate
-
-
?
glycocholic acid + NAD+
7alpha,12alpha-dihydroxy-5beta-cholan-3-one-24-oyl-glycine + NADH
-
-
-
-
?
oxidized 8-acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-azabenzo[de]anthracen-10-one + NAD(P)H
reduced 8-acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-azabenzo[de]anthracen-10-one + NAD(P)+
taurocholic acid + NAD(P)+
2[[7alpha,12alpha-dihydroxy-3,24-dioxo-5beta-cholan-24-yl]amino]ethane sulfonic acid + NADPH
taurocholic acid + NAD+
7alpha,12alpha-dihydroxy-5beta-cholan-3-one-24-oyl-taurine + NADH
-
-
-
-
?
testosterone + NADP+
4-androstene-3,17-dione + NADPH + H+
-
isozymes AKR1C1-AKR1C4
-
-
r
tibolone + NADPH
3alpha-hydroxytibolone + NADP+
-
isozyme AKR1C4 acts predominantly 3alpha-specific, isozyme AKR1C3 performs both 3alpha- and 3beta-reduction, tibolone is [7alpha,17alpha]-17-hydroxy-7-methyl-19-nor-pregn-5(10)-en-20-yn-3-one, or livial, a DELTA5(10)-ene-ketosteroid and a hormone replacement therapeutic used in the treatment of climacteric complaints and the prevention of osteoporosis, binding mode
-
-
r
tibolone + NADPH
3beta-hydroxytibolone + NADP+
-
isozyme AKR1C1 is stereospecific forming exclusively the beta-isomer, isozyme AKR1C2 is 3beta-specific with substrate tibolone, isozyme AKR1C3 performs both 3alpha- and 3 beta-reduction, tibolbone is [7alpha,17alpha]-17-hydroxy-7-methyl-19-nor-pregn-5(10)-en-20-yn-3-one, or livial, a DELTA5(10)-ene-ketosteroid and a hormone replacement therapeutic used in the treatment of climacteric complaints and the prevention of osteoporosis
-
-
r
ursodeoxycholate + NAD+
7beta-hydroxy-3-oxo-5beta-cholan-24-oic acid + NADH
-
-
-
-
r
ursodeoxycholic acid + NAD+
7alpha,12alpha-dihydroxy-5beta-cholan-3-one-24-oic acid + NADH
-
-
-
-
?
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
-
i.e. 3alpha,5alpha-tetrahydroprogesterone or 3alpha,5alpha-THP, the enzyme catalyzes the biosynthesis and oxidation of 3alpha,5alpha-reduced neurosteroids as allopregnanolone, which stimulates GABAA receptors, sciatic nerves-induced analgesia results in increased enzyme levels in neuropathic rats, overview
-
-
r
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
-
i.e. 3alpha,5alpha-tetrahydroprogesterone or 3alpha,5alpha-THP
-
-
r
3alpha,7alpha,12alpha-trihydroxy-5beta-cholanoyl glycine + NAD+
7alpha,12alpha-dihydroxy-5beta-cholan-3-one-24-oyl glycine + NADH
-
-
-
-
?
3alpha,7alpha,12alpha-trihydroxy-5beta-cholanoyl glycine + NAD+
7alpha,12alpha-dihydroxy-5beta-cholan-3-one-24-oyl glycine + NADH
-
-
-
-
?
3alpha-hydroxy-5beta-androstan-17-one + NADP+
5beta-androstan-3,17-dione + NADPH
-
-
-
r
3alpha-hydroxy-5beta-androstan-17-one + NADP+
5beta-androstan-3,17-dione + NADPH
-
-
-
-
r
3alpha-hydroxy-5beta-androstan-17-one + NADP+
5beta-androstan-3,17-dione + NADPH
-
-
-
-
r
3alpha-hydroxy-5beta-pregnan-20-one + NADP+
5beta-pregnan-3,20-dione + NADPH
-
inhibition by Mg2+ only in oxidative direction
-
-
r
3alpha-hydroxy-5beta-pregnan-20-one + NADP+
5beta-pregnan-3,20-dione + NADPH
-
-
-
-
r
3alpha-hydroxy-5beta-pregnan-20-one + NADP+
5beta-pregnan-3,20-dione + NADPH
-
-
-
-
r
4-nitroacetophenone + NADPH + H+
1-(4-nitrophenyl)ethanol + NADP+
-
-
-
-
?
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
17beta-hydroxy-5alpha-androstan-3-one + NADPH
-
-
-
-
r
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
17beta-hydroxy-5alpha-androstan-3-one + NADPH
-
-
-
r
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
17beta-hydroxy-5alpha-androstan-3-one + NADPH
-
-
-
-
r
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
17beta-hydroxy-5alpha-androstan-3-one + NADPH
-
-
-
r
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
17beta-hydroxy-5alpha-androstan-3-one + NADPH
-
-
-
-
-
5alpha-androstan-3alpha,17beta-diol + NAD(P)H
5alpha-dihydrotestosterone + NAD(P)+
-
-
-
r
5alpha-androstan-3alpha,17beta-diol + NAD(P)H
5alpha-dihydrotestosterone + NAD(P)+
-
-
-
-
r
5alpha-dihydroprogesterone + 2 NADPH + 2 H+
4-pregnen-3alpha,20beta-diol + 2 NADP+
-
-
-
?
5alpha-dihydroprogesterone + 2 NADPH + 2 H+
4-pregnen-3alpha,20beta-diol + 2 NADP+
inactivation of the potent androgen, 3alpha(beta)-hydroxysteroid oxidoreductase activity
-
-
ir
5alpha-dihydroprogesterone + 2 NADPH + 2 H+
4-pregnen-3alpha,20beta-diol + 2 NADP+
-
isozyme AKR1C4
-
-
r
5alpha-dihydroprogesterone + 2 NADPH + 2 H+
4-pregnen-3alpha,20beta-diol + 2 NADP+
-
preferred substrate for isozyme AKR1C4, while isozymes AKR1C1-3 show only low activity
-
-
r
5alpha-dihydroprogesterone + 2 NADPH + 2 H+
4-pregnen-3alpha,20beta-diol + 2 NADP+
-
isozyme AKR1C9
-
-
r
5alpha-dihydroprogesterone + NADPH
4-pregnen-3alpha,20beta-diol + NADP+
-
-
-
?
5alpha-dihydroprogesterone + NADPH
4-pregnen-3alpha,20beta-diol + NADP+
-
isozyme AKR1C2 acts 3alpha-specific on 5alpha-DHT, preferred substrate
-
-
r
5alpha-dihydroprogesterone + NADPH + H+
3alpha,5alpha-3-hydroxypregnan-20-one + NADP+
-
-
-
-
r
5alpha-dihydroprogesterone + NADPH + H+
3alpha,5alpha-3-hydroxypregnan-20-one + NADP+
-
in the CNS: both reaction directions by type 3 isozyme AKR1C2
-
-
r
5alpha-dihydroprogesterone + NADPH + H+
3alpha,5alpha-3-hydroxypregnan-20-one + NADP+
-
last step in neurosteroid allopregnanolone biosynthesis
-
-
?
5alpha-dihydroprogesterone + NADPH + H+
3alpha,5alpha-3-hydroxypregnan-20-one + NADP+
-
type 2 isozyme AKR1C3 catalyzes the forward reaction, type 3 isozyme AKR1C2 catalyzes the reverse reaction
-
-
ir
5alpha-dihydroprogesterone + NADPH + H+
3alpha,5alpha-3-hydroxypregnan-20-one + NADP+
-
type 3 isozyme AKR1C2
-
-
r
5alpha-dihydroprogesterone + NADPH + H+
3alpha,5alpha-3-hydroxypregnan-20-one + NADP+
-
-
-
-
?
5alpha-dihydroprogesterone + NADPH + H+
4-pregnen-3alpha,20beta-diol + NADP+
-
-
-
-
ir
5alpha-dihydroprogesterone + NADPH + H+
4-pregnen-3alpha,20beta-diol + NADP+
-
in the prostate: forward reaction by type 2 isozyme AKR1C3, reverse reaction by type 3 isozyme AKR1C2
-
-
ir
5alpha-dihydrotestosterone + NAD(P)H
3beta-adiol + NAD(P)+
-
i.e. 5alpha-androstan-17beta-ol-3-one
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
3beta-adiol + NAD(P)+
-
i.e. 5alpha-androstan-17beta-ol-3-one
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
3beta-adiol + NAD(P)+
-
i.e. 5alpha-androstan-17beta-ol-3-one
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
-
i.e. 5alpha-androstan-17beta-ol-3-one
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
-
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
-
-
-
-
?
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
-
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
-
i.e. 5alpha-androstan-17beta-ol-3-one
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
-
i.e. 5alpha-androstan-17beta-ol-3-one
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
-
i.e. 5alpha-androstan-17beta-ol-3-one
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
-
i.e. 5alpha-androstan-17beta-ol-3-one
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstan-3alpha,17beta-diol + NAD(P)+
-
i.e. 5alpha-androstan-17beta-ol-3-one
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
discussion of physiological role
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
-
-
?
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
-
-
?
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
NADH-linked, particulate enzyme prefers oxidative reaction, while the NADPH-linked, cytosolic enzyme prefers the reductive reaction
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
discussion of physiological role
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
discussion of physiological role
-
r
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
-
inactivation of the potent androgen in human prostate
-
-
r
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
-
inactivation of the potent androgen in human prostate, fluorometric activity measurement in intact cells, overview
-
-
?
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
-
i.e. DHT
-
-
?
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
-
i.e. DHT
-
-
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
-
-
-
?
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
i.e. DHT or 5alpha-androstane-17beta-ol-3-one, the reduction reaction is slightly preferred by the wild-type enzyme, which is determined by residue Arg276
i.e. 5alpha-androstane-3alpha,17beta-diol
-
?
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
-
-
-
r
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
-
-
-
r
5alpha-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5alpha-pregnan-20-one + NAD(P)+
-
-
-
?
5alpha-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5alpha-pregnan-20-one + NAD(P)+
-
-
-
?
5alpha-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5alpha-pregnan-20-one + NAD(P)+
-
-
-
r
5alpha-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5alpha-pregnan-20-one + NAD(P)+
-
5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity, utilizing NADH as cofactor when of particulate origin and NADPH when of cytosolic origin
-
?
5alpha-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5alpha-pregnan-20-one + NAD(P)+
-
5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity, utilizing NADH as cofactor when of particulate origin and NADPH when of cytosolic origin
-
?
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnane-3alpha-ol-20-one + NAD(P)+
-
5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity, NADPH and NADH possible as cofactors
-
?
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnane-3alpha-ol-20-one + NAD(P)+
-
5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity, utilizing NADH as cofactor when of particulate origin and NADPH when of cytosolic origin
-
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnane-3alpha-ol-20-one + NAD(P)+
-
5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity, utilizing NADH as cofactor when of particulate origin and NADPH when of cytosolic origin
-
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnane-3alpha-ol-20-one + NAD(P)+
-
5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity, utilizing NADH as cofactor when of particulate origin and NADPH when of cytosolic origin
-
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnane-3alpha-ol-20-one + NAD(P)+
-
5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity, utilizing NADH as cofactor when of particulate origin and NADPH when of cytosolic origin
-
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnane-3alpha-ol-20-one + NAD(P)+
-
activity higher during lactation in female rats
-
r
5alpha-pregnan-3,20-dione + NADPH
3alpha-hydroxy-5alpha-pregnan-20-one + NADP+
-
-
-
?
5alpha-pregnan-3,20-dione + NADPH
3alpha-hydroxy-5alpha-pregnan-20-one + NADP+
-
-
-
?
5alpha-pregnan-3,20-dione + NADPH
3alpha-hydroxy-5alpha-pregnan-20-one + NADP+
-
-
-
?
5alpha-pregnan-3,20-dione + NADPH
3alpha-hydroxy-5alpha-pregnan-20-one + NADP+
-
-
-
r
5alpha-pregnan-3,20-dione + NADPH
3alpha-hydroxy-5alpha-pregnan-20-one + NADP+
-
-
-
r
5alpha-pregnan-3,20-dione + NADPH
3alpha-hydroxy-5alpha-pregnan-20-one + NADP+
-
-
-
r
5beta-androstan-3,17-dione + NAD(P)H
5beta-androstan-17one-3-ol + NAD(P)+
-
-
-
-
r
5beta-androstan-3,17-dione + NAD(P)H
5beta-androstan-17one-3-ol + NAD(P)+
-
-
-
-
?
5beta-androstan-3,17-dione + NAD(P)H
5beta-androstan-17one-3-ol + NAD(P)+
-
-
-
-
r
5beta-androstan-3alpha,17beta-diol + NADP+
17beta-hydroxy-5beta-androstan-3-one + NADPH
-
-
-
-
r
5beta-androstan-3alpha,17beta-diol + NADP+
17beta-hydroxy-5beta-androstan-3-one + NADPH
-
-
-
-
r
5beta-androstan-3alpha,17beta-diol + NADP+
17beta-hydroxy-5beta-androstan-3-one + NADPH
-
-
-
-
r
5beta-dihydrotestosterone + NAD(P)H
5beta-androstan-3alpha,17beta-diol + NAD(P)+
-
-
-
-
?
5beta-dihydrotestosterone + NAD(P)H
5beta-androstan-3alpha,17beta-diol + NAD(P)+
-
-
-
-
?
5beta-dihydrotestosterone + NAD(P)H
5beta-androstan-3alpha,17beta-diol + NAD(P)+
-
-
-
?
5beta-dihydrotestosterone + NAD(P)H
5beta-androstan-3alpha,17beta-diol + NAD(P)+
-
-
-
-
?
5beta-dihydrotestosterone + NAD(P)H
5beta-androstan-3alpha,17beta-diol + NAD(P)+
-
NADH-linked, particulate enzyme prefers oxidative reaction, while the NADPH-linked, cytosolic enzyme prefers the reductive reaction
-
r
5beta-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5beta-pregnan-20-one + NAD(P)+
-
3alpha-hydroxysteroid-5beta-oxidoreductase activity
-
?
5beta-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5beta-pregnan-20-one + NAD(P)+
-
3alpha-hydroxysteroid-5beta-oxidoreductase activity
-
?
5beta-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5beta-pregnan-20-one + NAD(P)+
-
3alpha-hydroxysteroid-5beta-oxidoreductase activity
-
r
5beta-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5beta-pregnan-20-one + NAD(P)+
-
3alpha-hydroxysteroid-5beta-oxidoreductase activity
-
?
5beta-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5beta-pregnan-20-one + NAD(P)+
-
3alpha-hydroxysteroid-5beta-oxidoreductase activity
-
r
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADPH
9-[hydroxy(phenyl)methyl]-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADP+
-
competitive substrate, fluorometric activity measurement in intact cells, overview
-
-
?
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADPH
9-[hydroxy(phenyl)methyl]-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADP+
-
competitive substrate
-
-
?
a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
-
-
-
r
a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
-
-
-
r
androsterone + NAD(P)+
5alpha-androstan-3,17-dione + NAD(P)H
-
-
-
-
r
androsterone + NAD(P)+
5alpha-androstan-3,17-dione + NAD(P)H
-
i.e. 3alpha-hydroxy-5alpha-androstan-17-one
-
-
r
androsterone + NAD(P)+
5alpha-androstan-3,17-dione + NAD(P)H
-
i.e. 3alpha-hydroxy-5alpha-androstan-17-one
-
r
androsterone + NAD(P)+
5alpha-androstan-3,17-dione + NAD(P)H
-
i.e. 3alpha-hydroxy-5alpha-androstan-17-one
-
-
r
androsterone + NAD(P)+
5alpha-androstan-3,17-dione + NAD(P)H
-
i.e. 3alpha-hydroxy-5alpha-androstan-17-one
-
-
r
androsterone + NAD(P)+
5alpha-androstan-3,17-dione + NAD(P)H
-
i.e. 3alpha-hydroxy-5alpha-androstan-17-one
-
-
r
androsterone + NAD(P)+
5alpha-androstan-3,17-dione + NAD(P)H
-
i.e. 3alpha-hydroxy-5alpha-androstan-17-one
-
-
r
androsterone + NAD+
5alpha-androstan-3,17-dione + NADH + H+
-
-
-
-
?
androsterone + NAD+
5alpha-androstan-3,17-dione + NADH + H+
-
rate-limiting step in the reaction is the release of NADH
-
-
r
androsterone + NAD+
5alpha-androstane-3,17-dione + NADH
-
-
-
-
r
androsterone + NAD+
androstanedione + NADH
the intramolecular proton transfer is a rate-limiting step, with a concomitant releasing of protons to bulk solvent
-
-
r
androsterone + NADP+
androstane-3,17-dione + NADPH
-
isozymes AKR1C2, and AKR1C4
-
-
r
chenodeoxycholic acid + NAD(P)+
7alpha-hydroxy-3-oxo-5beta-cholan-24-oic acid + NAD(P)H
-
-
-
-
r
chenodeoxycholic acid + NAD(P)+
7alpha-hydroxy-3-oxo-5beta-cholan-24-oic acid + NAD(P)H
-
i.e. 3alpha,7alpha-dihydroxy-5beta-cholan-24-oic acid
-
-
r
chenodeoxycholic acid + NAD+
7alpha,12alpha-dihydroxy-5beta-cholan-3-one-24-oic acid + NADH
-
-
-
-
?
chenodeoxycholic acid + NAD+
7alpha,12alpha-dihydroxy-5beta-cholan-3-one-24-oic acid + NADH
-
-
-
-
?
cholic acid + NAD(P)+
7alpha,12alpha-dihydroxy-3-oxo-5beta-cholan-24-oic acid + NAD(P)H
-
-
-
-
r
cholic acid + NAD(P)+
7alpha,12alpha-dihydroxy-3-oxo-5beta-cholan-24-oic acid + NAD(P)H
-
-
-
?
cholic acid + NAD(P)+
7alpha,12alpha-dihydroxy-3-oxo-5beta-cholan-24-oic acid + NAD(P)H
-
-
-
?
cholic acid + NAD(P)+
7alpha,12alpha-dihydroxy-3-oxo-5beta-cholan-24-oic acid + NAD(P)H
-
-
-
-
?
cholic acid + NAD(P)+
7alpha,12alpha-dihydroxy-3-oxo-5beta-cholan-24-oic acid + NAD(P)H
-
i.e. 3alpha,7alpha,12alpha-trihydroxy-5beta-cholan-24-oic acid
-
-
?
cholic acid + NAD+
7alpha,12alpha-dihydroxy-5beta-cholan-3-one-24-oic acid + NADH
-
-
-
-
?
cholic acid + NAD+
7alpha,12alpha-dihydroxy-5beta-cholan-3-one-24-oic acid + NADH
-
-
-
-
?
deoxycholic acid + NAD(P)+
12alpha-hydroxy-3-oxo-5beta-cholan-24-oic acid + NAD(P)H + H+
-
-
-
-
?
deoxycholic acid + NAD(P)+
12alpha-hydroxy-3-oxo-5beta-cholan-24-oic acid + NAD(P)H + H+
-
i.e. 3alpha,12alpha-dihydroxy-5beta-cholan-24-oic acid
-
-
?
deoxycholic acid + NAD(P)+
12alpha-hydroxy-3-oxo-5beta-cholan-24-oic acid + NAD(P)H + H+
-
i.e. 3alpha,12alpha-dihydroxy-5beta-cholan-24-oic acid
-
-
?
deoxycholic acid + NADH
12alpha-hydroxy-3-oxo-5beta-cholan-24-oic acid + NAD+
-
-
-
-
r
deoxycholic acid + NADH
12alpha-hydroxy-3-oxo-5beta-cholan-24-oic acid + NAD+
-
-
-
r
glycolithocholic acid + NADP+
3-oxo-glycocholanoic acid + NADPH
-
i.e. 3alpha-hydroxy-5beta-cholanoyl glycine
-
-
?
glycolithocholic acid + NADP+
3-oxo-glycocholanoic acid + NADPH
-
i.e. 3alpha-hydroxy-5beta-cholanoyl glycine
-
-
?
lithocholic acid + NAD+
5beta-cholan-3-one-24-oic acid + NADH
-
-
-
-
?
lithocholic acid + NADP+
3-oxo-5beta-cholan-24-oic acid + NADPH
-
i.e. 3alpha-hydroxy-5beta-cholan-24-oic acid
-
-
?
lithocholic acid + NADP+
3-oxo-5beta-cholan-24-oic acid + NADPH
-
i.e. 3alpha-hydroxy-5beta-cholan-24-oic acid
-
-
?
oxidized 8-acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-azabenzo[de]anthracen-10-one + NAD(P)H
reduced 8-acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-azabenzo[de]anthracen-10-one + NAD(P)+
-
synthetic compound with fluorophore core
-
-
r
oxidized 8-acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-azabenzo[de]anthracen-10-one + NAD(P)H
reduced 8-acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-azabenzo[de]anthracen-10-one + NAD(P)+
-
synthetic compound with fluorophore core
-
-
r
oxidized 8-acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-azabenzo[de]anthracen-10-one + NAD(P)H
reduced 8-acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-azabenzo[de]anthracen-10-one + NAD(P)+
-
synthetic compound with fluorophore core
-
-
r
p-nitrobenzaldehyde + NAD(P)H
p-nitrobenzylalcohol + NAD(P)+
-
-
-
r
pregn-4-en-3,20-dione + NADPH + H+
3alpha-hydroxypregn-4-en-20-one + NADP+
-
-
-
r
pregn-4-en-3,20-dione + NADPH + H+
3alpha-hydroxypregn-4-en-20-one + NADP+
progesterone
allopregnanolone
-
r
pregn-4-en-3,20-dione + NADPH + H+
3alpha-hydroxypregn-4-en-20-one + NADP+
progesterone
allopregnanolone
-
r
taurocholic acid + NAD(P)+
2[[7alpha,12alpha-dihydroxy-3,24-dioxo-5beta-cholan-24-yl]amino]ethane sulfonic acid + NADPH
-
-
-
-
?
taurocholic acid + NAD(P)+
2[[7alpha,12alpha-dihydroxy-3,24-dioxo-5beta-cholan-24-yl]amino]ethane sulfonic acid + NADPH
-
i.e. 3alpha,7alpha,12alpha-trihydroxy-5beta-cholanoyl taurine
-
-
?
testosterone + NADPH
?
-
residues involved in substrate binding are T24, L54, F118, T226, W227, N306, and Y310
-
-
?
testosterone + NADPH
?
-
substrate binding residues are T24, L54, Y55, H117, F118, F129, T226, W227, N306, and Y310
-
-
?
tibolone + NADPH
3-hydroxytibolone + NADP+
-
tibolone is used to treat climacteric symptoms and prevent osteoporosis, it exerts tissue-selective effects via site-specific metabolism into 3alpha- and 3beta-hydroxymetabolites and a DELTA4-isomer
-
-
?
tibolone + NADPH
3-hydroxytibolone + NADP+
-
i.e. [7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, stereoselctive reaction to the 3alpha-hydroxytibolone product
-
-
?
tibolone + NADPH
3-hydroxytibolone + NADP+
-
i.e. [7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, stereoselective reaction to the 3alpha-hydroxytibolone product
-
-
?
additional information
?
-
-
reduction of carbonyl compounds e.g. quinones, aliphatic-chain diketones, ketones
-
-
-
additional information
?
-
-
can not catalyze the dehydrogenation of 3beta-hydroxysteroids, epiandrosterone and 17beta-hydroxysteroids, i.e. testosterone and 17beta-estradiol
-
-
-
additional information
?
-
-
bifunctional enzyme also catalyzing the reaction of carbonyl reductase, EC 1.1.1.184
-
-
-
additional information
?
-
-
the enzyme catalyzes reversibly the oxidoreduction of 3alpha-hydroxyl groups of steroid hormones
-
-
-
additional information
?
-
the enzyme catalyzes reversibly the oxidoreduction of 3alpha-hydroxyl groups of steroid hormones
-
-
-
additional information
?
-
-
a saturated 4,5 double bound is essential for enzyme activity, 3-ketosteroids are not used as substrates
-
-
-
additional information
?
-
-
can not catalyze conversion of 3alpha-androstanediol to 5alpha-dihydrotestosterone
-
-
-
additional information
?
-
-
type 3 isoform in liver virtually identical with bile acid-binding protein
-
-
-
additional information
?
-
-
due to inhibition by NADPH, the isozymes acts only as 3-ketosteroid reductases in vivo
-
-
-
additional information
?
-
-
enzyme inactivates steroid hormones in the liver, regulates 5alpha-dihydrotestosterone levels in the prostate, and forms the neurosteroid allopregnanolone in the CNS, isozymes might be involved in regulation of the levels of active androgens, estrogens, and progestrins
-
-
-
additional information
?
-
in vivo the isozymes act predominantly as 3-ketosteroid reductases due to inhibition by NADPH, but significantly produce 3beta-tetrahydrosteroids physiologically important in steroid metabolim, androgen metabolism, overview
-
-
-
additional information
?
-
-
isozyme AKR1C2 is involved in neurosteroid biosynthesis, while isozyme AKE1C1 eliminates the neurosteroid precursor from the pathway and decreases the neurosteroid concentration in the brain, pathway overview
-
-
-
additional information
?
-
-
physiological roles of the isozymes AKR1C1-4, overview, enzyme regulates the occupancy and trans-activation of steroid hormone receptors by interconverting potent hormones with their cognate inactive metabolites
-
-
-
additional information
?
-
-
role of the isozymes in bile acid biosynthesis and steroid metabolism, product profiling, pre-receptor regulation of steroid hormone action, overview
-
-
-
additional information
?
-
-
isozymes AKR1C1, AKR1C4, and AKR1C2 show broad enzyme specificities, overview
-
-
-
additional information
?
-
-
isozymes display 3alpha-, 17beta-, and 20alpha-hydroxysteroid dehydrogenase activities to varying degrees, isozyme AKR1C4 shows the highest 3alpha-hydroxysteroid dehydrogenase activity of all isozymes, overview
-
-
-
additional information
?
-
-
molecular docking experiments using the crystal structures of isozymes AKR1C1 and AKR1C2 reveal the structural basis for stereospecificity of the isozymes
-
-
-
additional information
?
-
stereospecificity differs between the isozymes, the enzyme also exhibits in vitro 3alpha[17beta]-hydroxysteroid axidase activity with 3alpha-diol as the substrate
-
-
-
additional information
?
-
-
structure-function study, the isozymes provide 3alpha-, 17beta-, and 20alpha-hydroxysteroid oxidase activity as well as 3-, 17-, and 20-ketosteroid reductase activity in vitro
-
-
-
additional information
?
-
-
AKR1C3 catalyzes androgen, estrogen, and prostaglandin metabolism, AKR1C3 is also involved in cancer development or progression
-
-
-
additional information
?
-
-
type I human hepatic 3alpha-hydroxysteroid dehydrogenase plays a significant role in bile acid biosynthesis, steroid hormone metabolism, and xenobiotic metabolism, the enzyme is regulated by expression level of the liver X receptor alpha, i.e. LXRalpha [NR1H3], a nuclear hormone receptor, predictive response element modeling and whole genome analysis of LXRalpha occupancy sites using ChIP/microarray technology, overview
-
-
-
additional information
?
-
-
AKR1C2 and AKR1C3 also possesse prostaglandin 9- and 11-reductase activities, EC 1.1.1.188 and EC 1.1.1.189, respectively, overview
-
-
-
additional information
?
-
-
reduction of carbonyl compounds e.g. quinones, aliphatic-chain diketones, ketones
-
-
-
additional information
?
-
-
absolutely specific for 3alpha-hydroxy group of C19, C21 and C24 steroids
-
-
-
additional information
?
-
-
acts faster on A/B cis hydroxysteroids than on A/B trans hydroxysteroids
-
-
-
additional information
?
-
-
absolutely specific for 3alpha-hydroxy group of C19, C21 and C24 steroids
-
-
-
additional information
?
-
-
belongs to the group of Y'bile acid binders, bile acid metabolizing enzymes
-
-
-
additional information
?
-
-
broad steroid substrate and cofactor specificity, no 3-oxosteroid reduction of testosterone
-
-
-
additional information
?
-
-
the enzyme catalyzes the reversible interconversion of hydroxyl and oxo groups at position 3 of the steroid nucleus
-
-
-
additional information
?
-
-
broad steroid substrate and cofactor specificity, no 3-oxosteroid reduction of testosterone
-
-
-
additional information
?
-
-
the enzyme catalyzes the reversible interconversion of hydroxyl and oxo groups at position 3 of the steroid nucleus
-
-
-
additional information
?
-
-
substrate specificity of various isozymes
-
-
-
additional information
?
-
-
belongs to the group of Y'bile acid binders, bile acid metabolizing enzymes
-
-
-
additional information
?
-
-
enzyme inactivates steroid hormones in the liver, regulates 5alpha-dihydrotestosterone levels in the prostate, and forms the neurosteroid allopregnanolone in the CNS
-
-
-
additional information
?
-
-
enzyme plays a pivotal role in the inactivation of circulating steroid hormones
-
-
-
additional information
?
-
-
enzyme regulates the occupancy and trans-activation of steroid hormone receptors by interconverting potent hormones with their cognate inactive metabolites
-
-
-
additional information
?
-
-
the high 3alpha-oxidoreductase activity in the hypothalamus of prepubertal rats is not related to the gonadal or adrenal steroids, the products are found in both prepubertal, mature, and castrated rats, rats with adrenalectomy show elevated enzyme activities, 3alpha-hydroxy progesterone is not related to the regulation of gonadotropin secretion in the male rat
-
-
-
additional information
?
-
-
enzyme acts positional and stereospecific, structure-function relationship
-
-
-
additional information
?
-
-
isozyme is positional- and stereospecific for the 3alpha-hydroxy steroid dehydrogenase reaction
-
-
-
additional information
?
-
-
wild-type enzyme recognizes only the 3-keto function of steroids, while the substrate binding residue-mutant enzymes show a broader substrate specificity and broader reaction spectra, overview, structure-function study on the basis of the crystal structure, modeling
-
-
-
additional information
?
-
-
AKR1C9 catalyzes androgen, estrogen, and prostaglandin metabolism
-
-
-
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
-
-
-
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3alpha,5alpha-allopregnenolone + NAD(P)+
5alpha-dihydroprogesterone + NAD(P)H
-
i.e. 3alpha,5alpha-tetrahydroprogesterone or 3alpha,5alpha-THP, the enzyme catalyzes the biosynthesis and oxidation of 3alpha,5alpha-reduced neurosteroids as allopregnanolone, which stimulates GABAA receptors, sciatic nerves-induced analgesia results in increased enzyme levels in neuropathic rats, overview
-
-
r
3alpha-hydroxy-5alpha-pregnan-20-one + NADP+
5alpha-pregnan-3,20-dione + NADPH + H+
-
-
-
-
r
3alpha-hydroxypregn-4-en-20-one + NADP+
pregn-4-en-3,20-dione + NADPH + H+
-
-
-
-
?
4-pregnen-3alpha,20beta-diol + NAD+
(20beta)-20-hydroxypregn-4-en-3-one + NADH + H+
Q04828
-
-
-
ir
5alpha-dihydroprogesterone + NAD(P)H
4-pregnen-3alpha,20beta-diol + NAD(P)+
-
-
-
-
?
5alpha-dihydroprogesterone + NADPH
4-pregnen-3alpha,20beta-diol + NADP+
Q04828
-
-
-
?
5alpha-dihydroprogesterone + NADPH + H+
4-pregnen-3alpha,20beta-diol + NADP+
-
in the prostate: forward reaction by type 2 isozyme AKR1C3, reverse reaction by type 3 isozyme AKR1C2
-
-
ir
5alpha-dihydrotestosterone + NADH
3alpha-androstanediol + NAD+
-
reaction direction is regulated by the NAD+:NADPH relation in the cell
-
-
r
5alpha-dihydrotestosterone + NADPH
5alpha-androstane-3alpha,17beta-diol + NADP+
-
-
-
-
?
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADPH
9-[hydroxy(phenyl)methyl]-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one + NADP+
-
competitive substrate, fluorometric activity measurement in intact cells, overview
-
-
?
androsterone + NAD+
5alpha-androstane-3,17-dione + NADH
-
-
-
-
r
tibolone + NADPH
3-hydroxytibolone + NADP+
-
tibolone is used to treat climacteric symptoms and prevent osteoporosis, it exerts tissue-selective effects via site-specific metabolism into 3alpha- and 3beta-hydroxymetabolites and a DELTA4-isomer
-
-
?
5alpha-dihydroprogesterone + 2 NADPH + 2 H+
4-pregnen-3alpha,20beta-diol + 2 NADP+
Q04828
inactivation of the potent androgen, 3alpha(beta)-hydroxysteroid oxidoreductase activity
-
-
ir
5alpha-dihydroprogesterone + 2 NADPH + 2 H+
4-pregnen-3alpha,20beta-diol + 2 NADP+
-
isozyme AKR1C4
-
-
r
5alpha-dihydroprogesterone + 2 NADPH + 2 H+
4-pregnen-3alpha,20beta-diol + 2 NADP+
-
isozyme AKR1C9
-
-
r
5alpha-dihydroprogesterone + NADPH + H+
3alpha,5alpha-3-hydroxypregnan-20-one + NADP+
-
in the CNS: both reaction directions by type 3 isozyme AKR1C2
-
-
r
5alpha-dihydroprogesterone + NADPH + H+
3alpha,5alpha-3-hydroxypregnan-20-one + NADP+
-
last step in neurosteroid allopregnanolone biosynthesis
-
-
?
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
discussion of physiological role
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
Q59718
-
-
-
?
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
Q59718
-
-
-
?
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
-
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
NADH-linked, particulate enzyme prefers oxidative reaction, while the NADPH-linked, cytosolic enzyme prefers the reductive reaction
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
discussion of physiological role
-
-
r
5alpha-dihydrotestosterone + NAD(P)H
5alpha-androstane-3alpha,17beta-diol + NAD(P)+
-
discussion of physiological role
-
r
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
-
inactivation of the potent androgen in human prostate
-
-
r
5alpha-dihydrotestosterone + NADPH
3alpha-androstanediol + NADP+
-
inactivation of the potent androgen in human prostate, fluorometric activity measurement in intact cells, overview
-
-
?
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
P52895
-
-
-
r
5alpha-dihydrotestosterone + NADPH + H+
5alpha-androstane-3alpha,17beta-diol + NADP+
Q04828
-
-
-
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnane-3alpha-ol-20-one + NAD(P)+
-
5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity, NADPH and NADH possible as cofactors
-
?
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnane-3alpha-ol-20-one + NAD(P)+
-
5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity, utilizing NADH as cofactor when of particulate origin and NADPH when of cytosolic origin
-
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnane-3alpha-ol-20-one + NAD(P)+
-
5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity, utilizing NADH as cofactor when of particulate origin and NADPH when of cytosolic origin
-
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnane-3alpha-ol-20-one + NAD(P)+
-
5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity, utilizing NADH as cofactor when of particulate origin and NADPH when of cytosolic origin
-
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnane-3alpha-ol-20-one + NAD(P)+
-
5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity, utilizing NADH as cofactor when of particulate origin and NADPH when of cytosolic origin
-
r
5alpha-pregnan-3,20-dione + NAD(P)H + H+
5alpha-pregnane-3alpha-ol-20-one + NAD(P)+
-
activity higher during lactation in female rats
-
r
5alpha-pregnan-3,20-dione + NADPH
3alpha-hydroxy-5alpha-pregnan-20-one + NADP+
-
-
-
r
5alpha-pregnan-3,20-dione + NADPH
3alpha-hydroxy-5alpha-pregnan-20-one + NADP+
-
-
-
r
5alpha-pregnan-3,20-dione + NADPH
3alpha-hydroxy-5alpha-pregnan-20-one + NADP+
-
-
-
r
5beta-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5beta-pregnan-20-one + NAD(P)+
-
3alpha-hydroxysteroid-5beta-oxidoreductase activity
-
?
5beta-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5beta-pregnan-20-one + NAD(P)+
-
3alpha-hydroxysteroid-5beta-oxidoreductase activity
-
?
5beta-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5beta-pregnan-20-one + NAD(P)+
-
3alpha-hydroxysteroid-5beta-oxidoreductase activity
-
?
5beta-pregnan-3,20-dione + NAD(P)H
3alpha-hydroxy-5beta-pregnan-20-one + NAD(P)+
-
3alpha-hydroxysteroid-5beta-oxidoreductase activity
-
r
a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
P80702
-
-
-
r
a 3alpha-hydroxysteroid + NAD+
a 3-oxosteroid + NADH + H+
Q9I1X3
-
-
-
r
pregn-4-en-3,20-dione + NADPH + H+
3alpha-hydroxypregn-4-en-20-one + NADP+
P23457
progesterone
allopregnanolone
-
r
pregn-4-en-3,20-dione + NADPH + H+
3alpha-hydroxypregn-4-en-20-one + NADP+
P23457
progesterone
allopregnanolone
-
r
additional information
?
-
-
the enzyme catalyzes reversibly the oxidoreduction of 3alpha-hydroxyl groups of steroid hormones
-
-
-
additional information
?
-
P80702
the enzyme catalyzes reversibly the oxidoreduction of 3alpha-hydroxyl groups of steroid hormones
-
-
-
additional information
?
-
-
type 3 isoform in liver virtually identical with bile acid-binding protein
-
-
-
additional information
?
-
-
due to inhibition by NADPH, the isozymes acts only as 3-ketosteroid reductases in vivo
-
-
-
additional information
?
-
-
enzyme inactivates steroid hormones in the liver, regulates 5alpha-dihydrotestosterone levels in the prostate, and forms the neurosteroid allopregnanolone in the CNS, isozymes might be involved in regulation of the levels of active androgens, estrogens, and progestrins
-
-
-
additional information
?
-
Q04828
in vivo the isozymes act predominantly as 3-ketosteroid reductases due to inhibition by NADPH, but significantly produce 3beta-tetrahydrosteroids physiologically important in steroid metabolim, androgen metabolism, overview
-
-
-
additional information
?
-
-
isozyme AKR1C2 is involved in neurosteroid biosynthesis, while isozyme AKE1C1 eliminates the neurosteroid precursor from the pathway and decreases the neurosteroid concentration in the brain, pathway overview
-
-
-
additional information
?
-
-
physiological roles of the isozymes AKR1C1-4, overview, enzyme regulates the occupancy and trans-activation of steroid hormone receptors by interconverting potent hormones with their cognate inactive metabolites
-
-
-
additional information
?
-
-
role of the isozymes in bile acid biosynthesis and steroid metabolism, product profiling, pre-receptor regulation of steroid hormone action, overview
-
-
-
additional information
?
-
-
AKR1C3 catalyzes androgen, estrogen, and prostaglandin metabolism, AKR1C3 is also involved in cancer development or progression
-
-
-
additional information
?
-
-
type I human hepatic 3alpha-hydroxysteroid dehydrogenase plays a significant role in bile acid biosynthesis, steroid hormone metabolism, and xenobiotic metabolism, the enzyme is regulated by expression level of the liver X receptor alpha, i.e. LXRalpha [NR1H3], a nuclear hormone receptor, predictive response element modeling and whole genome analysis of LXRalpha occupancy sites using ChIP/microarray technology, overview
-
-
-
additional information
?
-
-
belongs to the group of Y'bile acid binders, bile acid metabolizing enzymes
-
-
-
additional information
?
-
-
belongs to the group of Y'bile acid binders, bile acid metabolizing enzymes
-
-
-
additional information
?
-
-
enzyme inactivates steroid hormones in the liver, regulates 5alpha-dihydrotestosterone levels in the prostate, and forms the neurosteroid allopregnanolone in the CNS
-
-
-
additional information
?
-
-
enzyme plays a pivotal role in the inactivation of circulating steroid hormones
-
-
-
additional information
?
-
-
enzyme regulates the occupancy and trans-activation of steroid hormone receptors by interconverting potent hormones with their cognate inactive metabolites
-
-
-
additional information
?
-
-
the high 3alpha-oxidoreductase activity in the hypothalamus of prepubertal rats is not related to the gonadal or adrenal steroids, the products are found in both prepubertal, mature, and castrated rats, rats with adrenalectomy show elevated enzyme activities, 3alpha-hydroxy progesterone is not related to the regulation of gonadotropin secretion in the male rat
-
-
-
additional information
?
-
-
AKR1C9 catalyzes androgen, estrogen, and prostaglandin metabolism
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3-acetylpyridine adenine dinucleotide
-
i.e. APAD+, 42% of the activity with NAD+ when cholic acid is utilized as substrate
nicotinamide hypoxanthine dinucleotide
-
i.e. deamino-NAD+, 36% of the activity with NAD+ when cholic acid is utilized as substrate
NAD+
-
oxidation utilizing NAD+ as a cofactor is the preferred reaction in vitro
NAD+
-
preferred by AKR1C17, dependent on, residues Gln270 and Glu276 are important for cofactor specificity, overview
NADH
-
cytosolic 5beta-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity
NADH
-
plasma membrane NADH-linked 5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity
NADH
-
NADH association to enzyme involves a bimolecular binding step and isomerization. The binding of NADH into a hydrophobic pocket in the active site restricts its motion and shields the fluorescence quenching from solvent
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
-
NADPH-linked microsomal 5beta-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase shows very low activity only with NADPH
NADPH
-
cytosolic NADPH-linked 5alpha-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase activity
NADPH
-
loose association of the NADP(H) is followed by two conformational changes, which increases cofactor affinity by 86fold
thio-NAD+
-
47% of the activity with NAD+ when cholic acid is utilized as substrate, preferably utilized with substrate fusidic acid
additional information
-
see also EC 1.1.1.213 for enzymes catalyzing the same reaction but with A-specificity concerning the cofactor, all enzymes without information of stereospecificity for cofactors are included in EC 1.1.1.50, but some of those may in fact belong to EC 1.1.1.213
-
additional information
-
cytosolic and microsomal enzymes have different cofactor preferences: cytosolic enzymes prefer NADP+/NADPH, microsomal prefer NAD+/NADH
-
additional information
-
kinetic model involving cofactor-enzyme complex formation kinetics
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
no effect by 0.5 mM of Mg2+, Ni2+, and Al3+
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one
-
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
cloxazolam
-
potent and specific, competitive inhibition of isozymes AKR1C1, AKR1C4, and AKR1C2
Ibuprofen
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.017 mM in fluorometric assay, in vitro IC50: 0.009 mM in fluorometric assay
naproxen
-
synthetic, nonsteroidal anti-inflammatory inhibitor, in vivo IC50: 0.0094 mM in fluorometric assay, 0.016 mM in radiometric assay, in vitro IC50: 0.0027 mM in fluorometric assay
Phenolphthalein
-
AKR1C4-selective inhibitor, in vitro and in vivo inhibition, IC50: 0.0004 mM
Flufenamic acid
-
nonsteroidal anti-inflammatory drug, inhibits all 4 isozymes, binding mode
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
NADPH
-
strongly inhibits the oxidation of 3-hydroxymetabolites in vivo and in vitro, determining the role of enzymes as 3-ketosteroid reductases in vivo, overview
NADPH
-
strongly inhibits the oxidation of 3-hydroxymetabolites in vivo and in vitro, determining the role of enzymes as 3-ketosteroid reductases in vivo, no inhibition of tibolone reduction in vitro, overview
ursodeoxycholate
-
forward reaction: competitive against 5alpha-dihydroprogesteroneand noncompetitive against NADPH, reverse reaction: competitive against allopregnanolone and noncompetitive against NADP+
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
additional information
-
no inhibition by oxazolam and oxazepam, benzodiazepams inhibit competitive versus the steroid substrates
-
additional information
-
no inhibition by the bile acid 5beta-cholanic acid-3alpha,7alpha-diol
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-butyl-3-methylimidazolium L-lactate
-
activates the enzyme as 5% co-solvent in Tris-HCl buffer, overview; 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
fluoxetine
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activates allopregnanolone formation in vivo, not in vitro at a concentration up to 0.05 mM, therefore in vivo activation is probably not realized by enzyme activation but a different mechanism
additional information
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poor activation by 1-butyl-3-methylimidazolium trifluoromethanesulfonate and 1-butyl-3-methylimidazolium tetrafluoroborate
-
additional information
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the expression of 3alpha-HSD/CR is induced by 0.5 mM testosterone
-
additional information
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no in vitro activation by paroxetine, sertraline, norfluoxetine, carbamazepine, clozapine, flurbiprofen, and sulfobromophthalein at a concentration up to 0.05 mM
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additional information
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treatment with 0.002 mM T0901317 induces about 2fold AKR1C4 mRNA expression, liver X receptor alpha mediates transcriptional activation of the AKR1C4 gene, leading to increased AKR1C4 protein expression
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.017 - 0.042
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
0.069
(3alpha,5beta,7beta)-3,7-dihydroxycholan-24-oic acid
-
pH 8.5, 37°C, with cofactor NAD+
0.0027
(5beta,20R)-20-hydroxypregnan-3-one
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.2 - 0.8
4-Nitroacetophenone
-
also in this range: 2,3-hexanedione, 1-phenyl-1,2-propanedione, 2,3-pentanedione, pyridine-4-aldehyde, 2,3-butanedione
0.235
5beta-Pregnan-3alpha-ol-20-one
-
cytosolic NADH-linked 5beta-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase
0.0024
5beta-pregnane-3,20-dione
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.023
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.003
9-(phenylcarbonyl)-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f]pyrido[3,2,1-ij]quinolin-11-one
-
recombinant enzyme in intact COS-1 cells
0.004
Dehydrolithocholic acid
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.0025
oxidized 8-acetyl-2,3,5,6-tetrahydro-1H,4H-11-oxa-3a-azabenzo[de]anthracen-10-one
-
isozyme AKR1C3
0.017
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
-
NADP+, detection spectrophotometrically
0.019
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
-
NADP+, detection radio- or fluorometrically
0.022
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
-
pH 7.0, 37°C with NADP+
0.042
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
-
pH 7.0, 37°C with NAD+
0.022
1-Acenaphthenol
-
pH 7.4, 25°C, recombinant isozyme AKR1C1 and isozyme AKR1C2
0.002 - 0.0024
17beta-hydroxy-5alpha-androstan-3-one
-
also in this range: 3alpha,7alpha-dihydroxy-5beta-cholanoyl glycine
0.0012 - 0.0017
17beta-hydroxy-5beta-androstan-3-one
-
also in this range: 17alpha,21-dihydroxy-5beta-pregnan-3,11,20-trione, acenaphthequinone
0.0012 - 0.0017
17beta-hydroxy-5beta-androstan-3-one
-
also in this range: 5beta-dihydrotestosterone, rat epididymis
0.0012
5alpha-Androstan-3,17-dione
-
wild type enzyme, in 0.1 M HEPES at pH 7.5
0.0031
5alpha-Androstan-3,17-dione
-
mutant enzyme S114A, in 0.1 M HEPES at pH 7.5
0.00218
5alpha-dihydrotestosterone
pH 7.4, 37°C, recombinant wild-type enzyme
0.007 - 0.0083
5alpha-dihydrotestosterone
-
also in this range: 3alpha,12alpha-dihydroxy-5beta-cholanoyl glycine
0.007 - 0.0083
5alpha-dihydrotestosterone
-
also in this range: 3alpha-hydroxy-5beta-pregnan-17-one
0.007 - 0.0083
5alpha-dihydrotestosterone
-
also in this range: 3alpha-hydroxy-5alpha-androstan-17-one
0.007 - 0.0083
5alpha-dihydrotestosterone
-
also in this range: androstanedione
0.00035 - 0.00049
5beta-androstan-3,17-dione
-
also in this range: 5beta-pregnan-3,20-dione, 5alpha-androstan-3,17-dione
0.0021
5beta-androstane-3,17-dione
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.038
9,10-phenanthrenequinone
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.00044
androsterone
-
pH 9.0, 25°C, recombinant His-tagged mutant S114A/Y155F
0.0035
androsterone
-
pH 7.4, 25°C, recombinant isozyme AKR1C2 and isozyme AKR1C4
0.007
androsterone
-
pH 9.0, 25°C, recombinant His-tagged mutant S114A
0.065
androsterone
-
pH 9.0, 25°C, recombinant His-tagged mutant K159A
0.074
androsterone
-
pH 9.0, 25°C, recombinant His-tagged mutant Y155F
0.1
androsterone
-
pH 9.0, 25°C, recombinant His-tagged mutant Y155F/K159A
0.01 - 0.025
cholic acid
-
NAD+, 3alpha,7alpha,12alpha-trihydroxy-5beta-cholanoyl glycine
0.01 - 0.025
cholic acid
-
3alpha-hydroxy-5beta-androstan-17-one, 3alpha,21-dihydroxy-5beta-pregnan-20-one, 5beta-androstan-3alpha,17beta-diol, 5alpha-androstan-3alpha,17beta-diol, NADP+
0.0052 - 0.0059
glycolithocholic acid
-
also in this range: 3alpha-hydroxy-5alpha-pregnan-20-one
0.0038
NAD+
-
wild type enzyme, in 0.1 M CAPS buffer, at pH 10.2, at 25°C; wild-type, pH 10.2, 25°C
0.005
NAD+
-
mutant enzyme D249S, in 0.1 M CAPS buffer, at pH 10.2, at 25°C
0.009
NAD+
-
mutant D249K, pH 10.2, 25°C; mutant enzyme D249K, in 0.1 M CAPS buffer, at pH 10.2, at 25°C
0.016
NAD+
-
mutant D249A, pH 10.2, 25°C; mutant enzyme D249A, in 0.1 M CAPS buffer, at pH 10.2, at 25°C
0.004
NADH
-
wild type enzyme, in 0.1 M HEPES at pH 7.5; wild-type, pH 7.5, 25°C
0.0065
NADH
-
mutant enzyme S114A, in 0.1 M HEPES at pH 7.5; mutant S114A, pH 7.5, 25°C
0.4
NADH
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cytosolic NADH-linked 5beta-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase
0.91
NADPH
-
cytosolic NADH-linked 5beta-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase
1.33
NADPH
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microsomal NADPH-linked 5beta-dihydroprogesterone 3alpha-hydroxysteroid oxidoreductase
0.119
testosterone
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pH 7.4, 35°C, 3alpha-hydroxysteroid dehydrogenase activity
additional information
additional information
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values for various substrates and different isozymes
-
additional information
additional information
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kinetic modeling of an enzymatic cycling reaction
-
additional information
additional information
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steady-state kinetics, ternary complex, sequential, kinetic mechanism of allopregnanolone synthesis with the cofactor binding before the steroid and leaving after it
-
additional information
additional information
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kinetic mechanism, substrate binding mechanism of isozyme AKR1C2
-
additional information
additional information
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kinetic mechanism, substrate binding mechanism of isozyme AKR1C9, wild-type and mutant enzymes
-
additional information
additional information
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steady state kinetics, overview
-
additional information
additional information
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steady-state kinetics
-
additional information
additional information
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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
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equilibrium kinetics of wild-type and mutant enzymes
-
additional information
additional information
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kinetics in absence and presence of co-solvents, overview
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additional information
additional information
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cofactor kinetics of wild-type and mutant enzymes, overview
-
additional information
additional information
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steady-state, transient state kinetics, and kinetic isotope effects, kinetic analysis and mechanism, ordered bi-bi mechanism, detailed overview
-
additional information
additional information
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kinetics of wild-type and mutant enzymes in presence or absence of CAPS and methylamine, overview
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additional information
additional information
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steady-state kinetics, and stopped-flow study, kinetics of enzyme mutants P185A, P185G, T188A, and T188S showing an increase in kcat, Ka drosterone and KiNAD and equal primary isotope effects of DV and D(V/K)
-
additional information
additional information
steady-state kinetics
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.004 - 0.507
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
82
(3alpha,5beta,7beta)-3,7-dihydroxycholan-24-oic acid
-
pH 8.5, 37°C, with cofactor NAD+
0.115
(5beta,20R)-20-hydroxypregnan-3-one
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.047
5beta-androstane-3,17-dione
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.105
5beta-pregnane-3,20-dione
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.1
6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.022
Dehydrolithocholic acid
-
pH 7.4, 25°C, recombinant wild-type AKR1C17
0.0