BRENDA - Enzyme Database show
show all sequences of 1.1.1.270

Tibolone metabolism in human liver is catalyzed by 3alpha/3beta-hydroxysteroid dehydrogenase activities of the four isoforms of the aldo-keto reductase (AKR)1C subfamily

Steckelbroeck, S.; Oyesanmi, B.; Jin, Y.; Lee, S.H.; Kloosterboer, H.J.; Penning, T.M.; J. Pharmacol. Exp. Ther. 316, 1300-1309 (2006)

Data extracted from this reference:

Cloned(Commentary)
Commentary
Organism
quantitative expression analysis of AKR1C isozymes
Homo sapiens
Inhibitors
Inhibitors
Commentary
Organism
Structure
5beta-cholanic acid-3alpha,7alpha-diol
-
Homo sapiens
Flufenamic acid
in vitro and in vivo inhibition of AKR1C1
Homo sapiens
Localization
Localization
Commentary
Organism
GeneOntology No.
Textmining
cytosol
-
Homo sapiens
5829
-
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
additional information
Homo sapiens
tibolone is used to treat climacteric symptoms and prevent osteoporosis, it exerts tissue-selective effects via site-specific metabolism into 3alpha- and 3beta-hydroxymetabolites and a DELTA4-isomer, In Hep-G2 cell cytosol and intact cells tibolone is exclusively reduced to 3beta-hydroxytibolone, tibolone metabolism in human liver is catalyzed by 3alpha/3beta-hydroxysteroid dehydrogenase activities of the four isoforms of the aldo-keto reductase (AKR)1C subfamily, overview
?
-
-
-
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
-
isozymes AKR1C1 and AKR1C2
-
Source Tissue
Source Tissue
Commentary
Organism
Textmining
Hep-G2 cell
-
Homo sapiens
-
hepatocyte
primary, time-dependent reduction of tibolone into 3beta- and 3alpha-hydroxytibolone was observed again in a 4:1 ratio
Homo sapiens
-
liver
-
Homo sapiens
-
Substrates and Products (Substrate)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
additional information
tibolone is used to treat climacteric symptoms and prevent osteoporosis, it exerts tissue-selective effects via site-specific metabolism into 3alpha- and 3beta-hydroxymetabolites and a DELTA4-isomer, In Hep-G2 cell cytosol and intact cells tibolone is exclusively reduced to 3beta-hydroxytibolone, tibolone metabolism in human liver is catalyzed by 3alpha/3beta-hydroxysteroid dehydrogenase activities of the four isoforms of the aldo-keto reductase (AKR)1C subfamily, overview
675595
Homo sapiens
?
-
-
-
-
additional information
comparison of substrate specificity and enantioselectivity of AKR1C isozymes, overview
675595
Homo sapiens
?
-
-
-
-
[7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one + NADPH
i.e. tibolone, a synthetic hormone
675595
Homo sapiens
[7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-ol + NADP+
reaction product determination and analysis
-
-
-
Temperature Optimum [°C]
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
37
-
assay at
Homo sapiens
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
7.4
-
assay at
Homo sapiens
Cofactor
Cofactor
Commentary
Organism
Structure
NADPH
-
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
quantitative expression analysis of AKR1C isozymes
Homo sapiens
Cofactor (protein specific)
Cofactor
Commentary
Organism
Structure
NADPH
-
Homo sapiens
Inhibitors (protein specific)
Inhibitors
Commentary
Organism
Structure
5beta-cholanic acid-3alpha,7alpha-diol
-
Homo sapiens
Flufenamic acid
in vitro and in vivo inhibition of AKR1C1
Homo sapiens
Localization (protein specific)
Localization
Commentary
Organism
GeneOntology No.
Textmining
cytosol
-
Homo sapiens
5829
-
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
additional information
Homo sapiens
tibolone is used to treat climacteric symptoms and prevent osteoporosis, it exerts tissue-selective effects via site-specific metabolism into 3alpha- and 3beta-hydroxymetabolites and a DELTA4-isomer, In Hep-G2 cell cytosol and intact cells tibolone is exclusively reduced to 3beta-hydroxytibolone, tibolone metabolism in human liver is catalyzed by 3alpha/3beta-hydroxysteroid dehydrogenase activities of the four isoforms of the aldo-keto reductase (AKR)1C subfamily, overview
?
-
-
-
Source Tissue (protein specific)
Source Tissue
Commentary
Organism
Textmining
Hep-G2 cell
-
Homo sapiens
-
hepatocyte
primary, time-dependent reduction of tibolone into 3beta- and 3alpha-hydroxytibolone was observed again in a 4:1 ratio
Homo sapiens
-
liver
-
Homo sapiens
-
Substrates and Products (Substrate) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
additional information
tibolone is used to treat climacteric symptoms and prevent osteoporosis, it exerts tissue-selective effects via site-specific metabolism into 3alpha- and 3beta-hydroxymetabolites and a DELTA4-isomer, In Hep-G2 cell cytosol and intact cells tibolone is exclusively reduced to 3beta-hydroxytibolone, tibolone metabolism in human liver is catalyzed by 3alpha/3beta-hydroxysteroid dehydrogenase activities of the four isoforms of the aldo-keto reductase (AKR)1C subfamily, overview
675595
Homo sapiens
?
-
-
-
-
additional information
comparison of substrate specificity and enantioselectivity of AKR1C isozymes, overview
675595
Homo sapiens
?
-
-
-
-
[7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one + NADPH
i.e. tibolone, a synthetic hormone
675595
Homo sapiens
[7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-ol + NADP+
reaction product determination and analysis
-
-
-
Temperature Optimum [°C] (protein specific)
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
37
-
assay at
Homo sapiens
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
7.4
-
assay at
Homo sapiens
Other publictions for EC 1.1.1.270
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
740936
Ferrante
4-Methylzymosterone and other ...
Saccharomyces cerevisiae
Lipids
51
1103-1113
2016
-
1
-
-
3
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
741250
Chen
Metabolism of androstenone, 17 ...
Sus scrofa
PLoS ONE
10
e113194
2015
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
1
-
-
1
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
726098
Debieu
Role of sterol 3-ketoreductase ...
Botrytis cinerea
Pest Manag. Sci.
69
642-651
2013
-
-
-
-
1
-
5
-
1
1
-
-
-
5
-
-
-
-
-
1
-
-
3
-
1
-
-
-
1
-
-
1
-
-
-
-
-
-
1
-
1
-
-
5
-
-
1
1
-
-
-
-
-
-
-
1
-
-
3
-
1
-
-
-
1
-
-
-
-
2
2
-
-
-
740097
Layer
Characterization of a mutation ...
Mus musculus
Biochim. Biophys. Acta
1831
361-369
2013
-
-
-
-
-
-
-
-
-
-
-
-
-
4
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
724124
Endo
Characterization of rabbit ald ...
Oryctolagus cuniculus
Arch. Biochem. Biophys.
527
23-30
2012
-
-
1
-
4
-
14
20
1
-
1
1
-
3
-
-
1
-
-
6
-
-
27
-
1
-
-
21
1
-
-
2
-
-
14
-
-
1
2
-
4
-
14
14
-
20
1
-
1
1
-
-
-
1
-
6
-
-
27
-
1
-
-
21
1
-
-
-
-
3
3
-
-
-
702462
Taramino
Interactions of oxidosqualene ...
Saccharomyces cerevisiae
Biochim. Biophys. Acta
1801
156-162
2010
-
-
-
-
-
-
-
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
711300
Taramino
Divergent interactions involvi ...
Homo sapiens, Mus musculus
Biochim. Biophys. Acta
1801
1232-1237
2010
-
-
-
-
2
-
-
-
-
-
-
-
-
7
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
1
1
-
-
-
725813
Thomas
The functions of key residues ...
Homo sapiens
J. Steroid Biochem. Mol. Biol.
120
192-199
2010
-
1
1
-
6
-
1
-
-
-
-
-
-
2
-
-
1
-
-
6
-
-
7
-
1
-
-
-
1
-
-
2
4
-
-
-
1
1
2
-
6
-
-
1
4
-
-
-
-
-
-
-
-
1
-
6
-
-
7
-
1
-
-
-
1
-
-
-
-
3
3
-
-
-
673822
Tam
Activities of 3beta-HSD and ar ...
Taeniopygia guttata
Gen. Comp. Endocrinol.
150
26-33
2006
-
-
-
-
-
-
-
-
-
-
-
3
-
1
-
-
-
-
-
5
-
-
3
-
-
-
-
-
-
-
-
2
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
-
3
-
-
-
-
-
5
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
675595
Steckelbroeck
Tibolone metabolism in human l ...
Homo sapiens
J. Pharmacol. Exp. Ther.
316
1300-1309
2006
-
-
1
-
-
-
2
-
1
-
-
1
-
2
-
-
-
-
-
3
-
-
3
-
1
-
-
-
1
-
-
1
-
-
-
-
-
1
1
-
-
-
-
2
-
-
1
-
-
1
-
-
-
-
-
3
-
-
3
-
1
-
-
-
1
-
-
-
-
-
-
-
-
-
677144
Jin
Molecular docking simulations ...
Homo sapiens
Steroids
71
380-391
2006
-
-
-
-
-
-
-
-
2
-
-
-
-
2
-
-
-
1
-
-
4
-
5
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
-
-
2
-
-
-
-
-
-
-
-
-
4
-
5
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
656200
Steckelbroeck
Human cytosolic 3alpha-hydroxy ...
Homo sapiens
J. Biol. Chem.
279
10784-10795
2004
-
-
1
-
-
-
3
1
2
-
-
1
-
2
-
-
-
-
-
1
-
-
3
-
-
-
-
3
-
-
-
2
-
-
-
-
-
1
2
-
-
-
-
3
-
1
2
-
-
1
-
-
-
-
-
1
-
-
3
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
655348
Rizner
Human type 3 3alpha-hydroxyste ...
Homo sapiens
Endocrinology
144
2922-2932
2003
-
-
-
-
-
-
1
-
-
-
-
1
-
2
-
-
-
-
-
4
-
-
3
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
1
-
-
-
-
-
1
-
-
-
-
-
4
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
656795
Marijanovic
Closing the gap: Identificatio ...
Homo sapiens, Mus musculus
Mol. Endocrinol.
17
1715-1725
2003
-
-
2
-
1
-
-
-
2
-
-
2
-
5
-
-
-
-
-
5
-
-
4
-
-
-
-
-
-
-
-
2
-
-
-
-
-
2
2
-
1
-
-
-
-
-
2
-
-
2
-
-
-
-
-
5
-
-
4
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
723672
Mo
Protein-protein interactions a ...
Saccharomyces cerevisiae
Proc. Natl. Acad. Sci. USA
99
39-44
2002
-
-
-
-
-
-
-
-
1
-
-
-
-
5
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
286477
Huang
Gene structure, chromosomal lo ...
Homo sapiens
Biochim. Biophys. Acta
1520
124-130
2001
-
-
1
-
-
-
-
-
3
-
-
-
-
3
-
-
-
1
-
-
-
-
3
-
-
-
-
-
-
-
-
1
-
-
-
-
-
1
1
-
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
286474
Pascal
Plant sterol biosynthesis: ide ...
Zea mays
Arch. Biochem. Biophys.
312
260-271
1994
1
-
-
-
-
-
2
11
2
-
-
2
-
3
-
-
-
1
-
2
-
-
27
-
-
-
-
-
-
-
-
3
-
-
-
1
-
-
3
-
-
-
-
2
-
11
2
-
-
2
-
-
-
-
-
2
-
-
27
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
286476
Vanden Bossche
Effects of itraconazole on cyt ...
Cryptococcus neoformans
Antimicrob. Agents Chemother.
37
2101-2105
1993
-
-
-
-
-
-
1
-
-
-
-
1
-
5
-
-
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
1
-
-
-
-
-
1
-
-
-
-
-
-
-
-
3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
286478
De Launoit
Expression of liver-specific m ...
Rattus norvegicus
J. Biol. Chem.
267
4513-4517
1992
-
-
1
-
-
-
1
1
-
-
-
2
-
3
-
-
-
-
-
1
-
-
11
-
1
-
-
-
1
-
-
1
-
-
1
-
-
1
1
-
-
-
1
1
-
1
-
-
-
2
-
-
-
-
-
1
-
-
11
-
1
-
-
-
1
-
-
-
-
-
-
-
-
-
286473
Appelkvist
Presence of individual enzymes ...
Rattus norvegicus
Arch. Biochem. Biophys.
282
318-325
1990
1
-
-
-
-
-
-
-
4
-
-
2
-
2
-
-
-
-
-
1
-
-
3
-
1
-
-
-
-
-
-
1
-
-
-
1
-
-
1
-
-
-
-
-
-
-
4
-
-
2
-
-
-
-
-
1
-
-
3
-
1
-
-
-
-
-
-
-
-
-
-
-
-
-
286472
Billheimer
Solubilization and partial pur ...
Rattus norvegicus
Arch. Biochem. Biophys.
211
430-438
1981
2
1
-
-
-
4
2
2
2
-
1
3
-
1
-
-
1
-
-
1
1
-
7
-
1
-
-
-
1
-
-
2
-
-
-
2
1
-
2
-
-
4
-
2
-
2
2
-
1
3
-
-
-
1
-
1
1
-
7
-
1
-
-
-
1
-
-
-
-
-
-
-
-
-
286475
Wieland
A DNA-binding of mouse kidney ...
Mus musculus
Steroids
37
527-538
1981
-
-
-
-
-
-
-
-
2
-
-
1
-
2
-
-
-
-
-
4
-
-
7
-
1
-
2
-
-
-
-
1
-
-
-
-
-
-
1
-
-
-
-
-
-
-
2
-
-
1
-
-
-
-
-
4
-
-
7
-
1
-
2
-
-
-
-
-
-
-
-
-
-
-