Cloned (Comment) | Organism |
---|---|
overexpression of isozymes AKR1C1-AKR1C4 in Escherichia coli C41(DE3) | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
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 | Homo sapiens | |
tibolone | strong substrate inhibition of isozyme AKR1C2 | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | steady state kinetics, overview | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Homo sapiens | due to inhibition by NADPH, the isozymes acts only as 3-ketosteroid reductases in vivo | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q04828 | 4 isozymes AKR1C1-AKR1C4 | - |
Purification (Comment) | Organism |
---|---|
recombinant isozymes AKR1C1-AKR1C4 from Escherichia coli by DE52 ion exchange and Blue Sepharose chromatography, to homogeneity | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
liver | specific isozyme AKR1C4 | Homo sapiens | - |
Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
---|---|---|---|
0.00002 | - |
purified recombinant isozymes AKR1C1 and AKR1C3, substrate 3alpha-hydroxytibolone | Homo sapiens |
0.00015 | - |
purified recombinant isozyme AKR1C3, substrate 3beta-hydroxytibolone | Homo sapiens |
0.00079 | - |
purified recombinant isozyme AKR1C1, substrate 3beta-hydroxytibolone | Homo sapiens |
0.00653 | - |
purified recombinant isozyme AKR1C4, substrate 3beta-hydroxytibolone | Homo sapiens |
0.0188 | - |
purified recombinant isozyme AKR1C4, substrate 3alpha-hydroxytibolone | Homo sapiens |
0.0253 | - |
purified recombinant isozyme AKR1C2, substrate 3beta-hydroxytibolone | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
3alpha-hydroxytibolone + NAD+ | isozymes AKR1C2 and AKR1C4, no activity with isozyme AKR1C1 | Homo sapiens | tibolone + NADH | - |
r | |
3beta-hydroxytibolone + NAD+ | isozymes AKR1C2, AKR1C1, and AKR1C4 | Homo sapiens | tibolone + NADH | - |
r | |
5alpha-dihydroprogesterone + 2 NADPH + 2 H+ | isozyme AKR1C2 acts 3alpha-specific on 5alpha-DHT, preferred substrate | Homo sapiens | pregnan-3alpha,20beta-diol + 2 NADP+ | - |
r | |
additional information | due to inhibition by NADPH, the isozymes acts only as 3-ketosteroid reductases in vivo | Homo sapiens | ? | - |
? | |
additional information | molecular docking experiments using the crystal structures of isozymes AKR1C1 and AKR1C2 reveal the structural basis for stereospecificity of the isozymes | Homo sapiens | ? | - |
? | |
tibolone + NADPH + H+ | 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 | Homo sapiens | 3alpha-hydroxytibolone + NADP+ | - |
r | |
tibolone + NADPH + H+ | 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 | Homo sapiens | 3beta-hydroxytibolone + NADP+ | - |
r |
Synonyms | Comment | Organism |
---|---|---|
3alpha/3beta-hydroxysteroid dehydrogenase | - |
Homo sapiens |
AKR1C | - |
Homo sapiens |
More | the isozymes belong to the AKR1C subfamily of the aldo-keto-reductase AKR superfamily | Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.000016 | - |
3beta-hydroxytibolone | below, pH 7.0, 37°, isozyme AKR1C3 | Homo sapiens | |
0.000016 | - |
3alpha-hydroxytibolone | below, pH 7.0, 37°, isozymes AKR1C1 and AKR1C3 | Homo sapiens | |
0.0005 | - |
3beta-hydroxytibolone | pH 7.0, 37°, isozyme AKR1C1 | Homo sapiens | |
0.004 | - |
3beta-hydroxytibolone | pH 7.0, 37°, isozyme AKR1C4 | Homo sapiens | |
0.012 | - |
3alpha-hydroxytibolone | pH 7.0, 37°, isozyme AKR1C4 | Homo sapiens | |
0.016 | - |
3beta-hydroxytibolone | pH 7.0, 37°, isozyme AKR1C1 | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7 | - |
assay at | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NAD+ | - |
Homo sapiens | |
NADH | - |
Homo sapiens | |
NADP+ | - |
Homo sapiens | |
NADPH | - |
Homo sapiens |