Cloned (Comment) | Organism |
---|---|
- |
Homo sapiens |
AKR1C1, transient expression in COS-1 cells, and recombinant overexpression in Escherichia coli strain BL21(DE3), quantitative real-time PCR analysis | Homo sapiens |
AKR1C2, transient expression in COS-1 cells, and recombinant overexpression in Escherichia coli strain BL21(DE3), quantitative real-time PCR analysis | Homo sapiens |
AKR1C3, transient expression in COS-1 cells, and recombinant overexpression in Escherichia coli strain BL21(DE3), quantitative real-time PCR analysis | Homo sapiens |
AKR1C4, transient expression in COS-1 cells, and recombinant overexpression in Escherichia coli strain BL21(DE3), quantitative real-time PCR analysis | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | flufenamic acid inhibits the isozyme's 17beta-oxosteroid reductase activity | Homo sapiens | |
Phenolphthalein | strong inhibition | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | AKR1C isozymes kinetics analysis, steady-state Michaelis-Menten kinetics | Homo sapiens | |
0.00212 | - |
4-androstenedione | pH 7.4, 37°C | Homo sapiens | |
0.0023 | - |
4-hydroxyandrostenedione | pH 7.4, 37°C | Homo sapiens | |
0.00603 | - |
4-hydroxytestosterone | pH 7.4, 37°C | Homo sapiens | |
0.00622 | - |
4-hydroxytestosterone | pH 7.4, 37°C | Homo sapiens | |
0.00843 | - |
4-hydroxyandrostenedione | pH 7.4, 37°C | Homo sapiens | |
0.00884 | - |
dihydrotestosterone | pH 7.4, 37°C | Homo sapiens | |
0.00977 | - |
4-hydroxyandrostenedione | pH 7.4, 37°C | Homo sapiens | |
0.01029 | - |
dihydrotestosterone | pH 7.4, 37°C | Homo sapiens | |
0.0117 | - |
dihydrotestosterone | pH 7.4, 37°C | Homo sapiens | |
0.016 | - |
dihydrotestosterone | pH 7.4, 37°C | Homo sapiens | |
0.02687 | - |
4-hydroxytestosterone | pH 7.4, 37°C | Homo sapiens | |
0.03362 | - |
4-hydroxyandrostenedione | pH 7.4, 37°C | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | - |
Homo sapiens | 5829 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
4-hydroxyandrostenedione + NADPH + H+ | Homo sapiens | - |
3alpha,4beta-dihydroxy-5alpha-androstan-17-one + NADP+ | - |
? | |
dihydrotestosterone + NADPH + H+ | Homo sapiens | low activity | 4-androsten-3alpha,17beta-diol + NADP+ | - |
? | |
dihydrotestosterone + NADPH + H+ | Homo sapiens | high activity | 4-androsten-3alpha,17beta-diol + NADP+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P17516 | - |
- |
Homo sapiens | P42330 | - |
- |
Homo sapiens | P52895 | - |
- |
Homo sapiens | Q04828 | - |
- |
Purification (Comment) | Organism |
---|---|
- |
Homo sapiens |
recombinant enzyme from Escherichia coli strain BL21(DE3) | Homo sapiens |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
4-androstenedione + NADPH | the enzyme act as reductase for 4-hydroxyandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities | Homo sapiens | ? | - |
? | |
4-hydroxyandrostenedione + NADPH | the enzyme act as reductase for 4-hydroxandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities | Homo sapiens | ? | - |
? | |
4-hydroxyandrostenedione + NADPH | the enzyme act as reductase for 4-hydroxyandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities | Homo sapiens | ? | - |
? | |
4-hydroxyandrostenedione + NADPH + H+ | - |
Homo sapiens | 3alpha,4beta-dihydroxy-5alpha-androstan-17-one + NADP+ | - |
? | |
4-hydroxytestosterone + NADPH | the enzyme act as reductase for 4-hydroxandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities | Homo sapiens | ? | - |
? | |
4-hydroxytestosterone + NADPH | the enzyme act as reductase for 4-hydroxyandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities | Homo sapiens | ? | - |
? | |
4-hydroxytestosterone + NADPH + H+ | - |
Homo sapiens | 3alpha,4beta-dihydroxy-5alpha-androstan-17-ol + NADP+ | - |
? | |
dihydrotestosterone + NADPH | the enzyme act as reductase for 4-hydroxandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities | Homo sapiens | ? | - |
? | |
dihydrotestosterone + NADPH | the enzyme act as reductase for 4-hydroxyandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities | Homo sapiens | ? | - |
? | |
dihydrotestosterone + NADPH + H+ | low activity | Homo sapiens | 4-androsten-3alpha,17beta-diol + NADP+ | - |
? | |
dihydrotestosterone + NADPH + H+ | high activity | Homo sapiens | 4-androsten-3alpha,17beta-diol + NADP+ | - |
? | |
additional information | identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione and testosterone, and poor activity with 4-hydroxytestosterone (4-OHT) | Homo sapiens | ? | - |
- |
|
additional information | identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione, testosterone and poor activity with 4-hydroxytestosterone (4-OHT) | Homo sapiens | ? | - |
- |
|
additional information | identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with 4-androstenedione, testosterone, and 4-hydroxytestosterone (4-OHT) | Homo sapiens | ? | - |
- |
|
additional information | identification of metabolites by GC-MSMS in feeding experiments of recombinant COS-1 cells. Substrate specificity of recombinant AKR1C isozymes, overview. The isozymes also have 17beta-hydroxysteroid dehydrogenase activity. No activity with testosterone and 4-androstenedione | Homo sapiens | ? | - |
- |
|
testosterone + NADPH + H+ | the enzyme act as reductase for 4-hydroxyandrostenedione in both COS-1 cells and in reaction systems with purified enzymes. It exerts 3alpha-, 3beta-, and 17beta-hydroxysteroid dehydrogenase activities | Homo sapiens | ? | - |
? |
Subunits | Comment | Organism |
---|---|---|
? | x * 37000, recombinant AKR1C1, SDS-PAGE | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
3-alpha-HSD type 2 | UniProt | Homo sapiens |
3-alpha-HSD1 | UniProt | Homo sapiens |
3-alpha-hydroxysteroid dehydrogenase type 2 | UniProt | Homo sapiens |
3-alpha-hydroxysteroid dehydrogenase type I | UniProt | Homo sapiens |
3alpha-HSD | - |
Homo sapiens |
3alpha-hydroxysteroid dehydrogenase | - |
Homo sapiens |
AKR1C1 | - |
Homo sapiens |
AKR1C2 | - |
Homo sapiens |
AKR1C3 | - |
Homo sapiens |
AKR1C4 | - |
Homo sapiens |
aldo-keto reductase family 1 member C1 | UniProt | Homo sapiens |
aldo-keto reductase family 1 member C2 | UniProt | Homo sapiens |
aldo-keto reductase family 1 member C3 | UniProt | Homo sapiens |
type III 3-alpha-hydroxysteroid dehydrogenase | UniProt | 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 |
---|---|---|---|---|---|
0.00075 | - |
dihydrotestosterone | pH 7.4, 37°C | Homo sapiens | |
0.0038 | - |
4-androstenedione | pH 7.4, 37°C | Homo sapiens | |
0.0052 | - |
4-hydroxyandrostenedione | pH 7.4, 37°C | Homo sapiens | |
0.0078 | - |
4-hydroxytestosterone | pH 7.4, 37°C | Homo sapiens | |
0.01 | - |
4-hydroxytestosterone | pH 7.4, 37°C | Homo sapiens | |
0.017 | - |
4-hydroxyandrostenedione | pH 7.4, 37°C | Homo sapiens | |
0.0175 | - |
dihydrotestosterone | pH 7.4, 37°C | Homo sapiens | |
0.023 | - |
dihydrotestosterone | pH 7.4, 37°C | Homo sapiens | |
0.0245 | - |
4-hydroxyandrostenedione | pH 7.4, 37°C | Homo sapiens | |
0.025 | - |
4-hydroxytestosterone | pH 7.4, 37°C | Homo sapiens | |
0.026 | - |
dihydrotestosterone | pH 7.4, 37°C | Homo sapiens | |
0.032 | - |
testosterone | pH 7.4, 37°C | Homo sapiens | |
0.032 | - |
4-hydroxyandrostenedione | pH 7.4, 37°C | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADPH | usage of NADPH-Na4 to NADP-Na2 in enzyme activity assays | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
metabolism | human aldo-keto reductases (AKR1C1-AKR1C4, AKR1Cs) play an important role in the intracellular metabolism of steroids. All AKR1Cs have both 3alpha- and 3beta-HSD activities, AKR1C2 and AKR1C4 have a higher 3alpha-HSD activity, whereas AKR1C1 and AKR1C3 have a higher 3beta-HSD activity | Homo sapiens |
physiological function | the enzyme metabolizes the aromatase inhibitor formestane (4-hydroxandrostenedione, 4-OHA), which binds with high affinity to the androgen receptor, molecular docking and binding kinetics. All recombinant AKR1C isozymes reduce 4-androstenedione to testosterone presenting 17-oxo reductase activity. AKR1C3 is most active as a 17-oxosteroid reductase followed by AKR1C1 and then AKR1C2, whereas AKR1C4 only weakly reduces 4-androstenedione to testosterone. For dihydrotestosterone (DHT), all four enzymes exhibit both 3alpha/beta-oxoreductase activities to various degrees. The major sources of 3beta-diol are AKR1C1, AKR1C3, and AKR1C4, and that of 3alpha-diol is AKR1C2. In this set-up, isolated AKR1C4 preferentially catalysed the 3beta-reduction of DHT. Inhibition by phenolphthalein changes the stereoselectivity back to the normal 3alpha-reduction. For testosterone, the AKR1C isozymes have no catalytic function and even no oxidative 17beta-HSD activity. For 4-hydroxyandrostenedione (4-OHA), some AKR1Cs behave as 17beta-HSD or as 3beta-HSD, but all AKR1Cs convert 4-OHA to 3alpha,4beta-dihydroxy-5alpha-androstan-17-one, possibly reducing the oxo-group at C4, thereby eliminating the double bond to varying extent. AKR1C3 is most active as a 17-oxosteroid reductase. AKR1C4 shows higher activities of 4-oxo-reductase, 3alpha-HSD, and 3beta-HSD, producing the largest amount of 3alpha,4beta-dihydroxy-5alpha-androstan-17-one and 3beta,4beta-dihydroxy-5alpha-androstan-17-one. Like testosterone, 4-hydroxytestosterone (4-OHT) is not a good substrate for isozymes AKR1C1 and AKR1C2. In contrast to testosterone, 4-OHT undergoes some AKR1C catalysed metabolism. Both AKR1C3 and AKR1C4 have some oxidative 17beta-HSD activity, and AKR1C4 has additional obvious 4-5 double bond reductase and 3-oxoreductase activities, making a good production of to 3alpha,4beta-dihydroxy-5alpha-androstan-17-one. AKR1C3 predominantly catalyzes the reduction at C17 of 4-andostenedione as a first step, whereas it catalyzes the first step in the metabolism of 4-OHT as oxidative 17beta-HSD. Apparently, AKR1C4 also catalyses the way of 4-OHT via a special 17beta-hydroxy pathway to 3alpha-adiol, a pathway whereby the 17beta-OH-group is preserved | Homo sapiens |
kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.75 | - |
dihydrotestosterone | pH 7.4, 37°C | Homo sapiens | |
0.943 | - |
4-hydroxytestosterone | pH 7.4, 37°C | Homo sapiens | |
0.959 | - |
4-hydroxyandrostenedione | pH 7.4, 37°C | Homo sapiens | |
0.96 | - |
testosterone | pH 7.4, 37°C | Homo sapiens | |
1.29 | - |
4-hydroxytestosterone | pH 7.4, 37°C | Homo sapiens | |
1.43 | - |
dihydrotestosterone | pH 7.4, 37°C | Homo sapiens | |
1.63 | - |
4-hydroxytestosterone | pH 7.4, 37°C | Homo sapiens | |
1.7 | - |
dihydrotestosterone | pH 7.4, 37°C | Homo sapiens | |
1.8 | - |
4-androstenedione | pH 7.4, 37°C | Homo sapiens | |
2.25 | - |
4-hydroxyandrostenedione | pH 7.4, 37°C | Homo sapiens | |
2.9 | - |
4-hydroxyandrostenedione | pH 7.4, 37°C | Homo sapiens | |
2.98 | - |
dihydrotestosterone | pH 7.4, 37°C | Homo sapiens |