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Literature summary extracted from
- Human cytosolic 3alpha-hydroxysteroid dehydrogenases of the aldo-keto reductase superfamily display significant 3beta-hydroxysteroid dehydrogenase activity: implications for steroid hormone metabolism and action (2004), J. Biol. Chem., 279, 10784-10795.
Cloned(Commentary)
| EC Number | Cloned (Comment) | Organism |
|---|---|---|
| 1.1.1.50 | overexpression of isozymes AKR1C1-AKR1C4 in Escherichia coli | Homo sapiens |
| 1.1.1.270 | overexpression in Escherichia coli | Homo sapiens |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.1.1.50 | Flufenamic acid | nonsteroidal anti-inflammatory drug, inhibits all 4 isozymes, binding mode | Homo sapiens |  |
| 1.1.1.50 | NADPH | strongly inhibits the 3alpha-hydroxysteroid oxidase activity | Homo sapiens | |
| 1.1.1.270 | Flufenamic acid | inhibits 3alpha-diol versus 3beta-diol formation | Homo sapiens | |
| 1.1.1.270 | additional information | NADPH-dependent 3-ketosteroid reductase activity is not inhibited by NAD+ | Homo sapiens | |
| 1.1.1.270 | NADPH | potent inhibition of hydroxysteroid oxidase activity by low micromolar concentrations | Homo sapiens | |
KM Value [mM]
| EC Number | KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|---|
| 1.1.1.270 | 0.0043 | - |
17beta-hydroxy-5alpha-androstan-3-one | pH 7.0, 37°C, spectrophotometric analysis, formation of 3beta-androstanediol or 3alpha-androstanediol | Homo sapiens | |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 1.1.1.50 | cytosol | - |
Homo sapiens | 5829 | - |
| 1.1.1.270 | cytosol | - |
Homo sapiens | 5829 | - |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.1.1.50 | 4-pregnen-3alpha,20beta-diol + NAD+ | Homo sapiens | - |
(20beta)-20-hydroxypregn-4-en-3-one + NADH + H+ | - |
ir | |
| 1.1.1.50 | 5alpha-dihydroprogesterone + 2 NADPH + 2 H+ | Homo sapiens | - |
pregnan-3alpha,20beta-diol + 2 NADP+ | - |
? | |
| 1.1.1.50 | 5alpha-dihydroprogesterone + 2 NADPH + 2 H+ | Homo sapiens | inactivation of the potent androgen, 3alpha(beta)-hydroxysteroid oxidoreductase activity | pregnan-3alpha,20beta-diol + 2 NADP+ | - |
ir | |
| 1.1.1.50 | additional information | Homo sapiens | 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 | ? | - |
? | |
| 1.1.1.270 | 2 17beta-hydroxy-5alpha-androstan-3-one + 2 NADPH + 2 H+ | Homo sapiens | AKR1cs are a source of beta-tetrahydrosteroids. This is of physiological significance because the formation of 3beta-diol in contrast to 3alpha-diol is virtually irreversible, the 3beta-diol is a pro-apoptotic ligand for estrogen receptor beta, and 3beta-tetrahydrosteroids act as gamma-aminobutyric acid type A receptor antagonists | 5alpha-androstane-3beta,17beta-diol + 5alpha-androstane-3alpha,17beta-diol + 2 NADP+ | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 1.1.1.50 | Homo sapiens | Q04828 | 4 isozymes AKR1C1-AKR1C4 | - |
| 1.1.1.270 | Homo sapiens | Q04828 | - |
- |
Purification (Commentary)
| EC Number | Purification (Comment) | Organism |
|---|---|---|
| 1.1.1.50 | recombinant enzymes from Escherichia coli by DE52 and Blue Sepharose chromatography | Homo sapiens |
Source Tissue
| EC Number | Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|---|
| 1.1.1.50 | Hep-G2 cell | hepatoma cell, expresses isozymes AKR1C1-AKR1C3 | Homo sapiens | - |
| 1.1.1.270 | Hep-G2 cell | HepG2 cells which lack 3-ketohydroxysteroid reductase/DELTA5-4ketosteroid isomerase mRNA expression, but express AKR1C1-AKR1C3 are able to convert 17beta-hydroxy-5alpha-androstan-3-one to 3beta-androstanediol and 3alpha-androstanediol | Homo sapiens | - |
Specific Activity [micromol/min/mg]
| EC Number | Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|---|
| 1.1.1.50 | 0.0037 | - |
purified recombinant isozyme AKR1C3, substrate 4-pregnen-3alpha,20beta-diol | Homo sapiens |
| 1.1.1.50 | 0.0039 | - |
purified recombinant isozyme AKR1C1, substrate 4-pregnen-3alpha,20beta-diol | Homo sapiens |
| 1.1.1.50 | 0.119 | - |
purified recombinant isozyme AKR1C4, substrate 4-pregnen-3alpha,20beta-diol | Homo sapiens |
| 1.1.1.50 | 76.1 | - |
purified recombinant isozyme AKR1C2, substrate 4-pregnen-3alpha,20beta-diol | Homo sapiens |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.1.1.50 | 4-pregnen-3alpha,20beta-diol + NAD+ | - |
Homo sapiens | (20beta)-20-hydroxypregn-4-en-3-one + NADH + H+ | - |
? | |
| 1.1.1.50 | 4-pregnen-3alpha,20beta-diol + NAD+ | - |
Homo sapiens | (20beta)-20-hydroxypregn-4-en-3-one + NADH + H+ | - |
ir | |
| 1.1.1.50 | 5alpha-dihydroprogesterone + 2 NADPH + 2 H+ | - |
Homo sapiens | pregnan-3alpha,20beta-diol + 2 NADP+ | - |
? | |
| 1.1.1.50 | 5alpha-dihydroprogesterone + 2 NADPH + 2 H+ | inactivation of the potent androgen, 3alpha(beta)-hydroxysteroid oxidoreductase activity | Homo sapiens | pregnan-3alpha,20beta-diol + 2 NADP+ | - |
ir | |
| 1.1.1.50 | 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 | Homo sapiens | ? | - |
? | |
| 1.1.1.50 | additional information | stereospecificity differs between the isozymes, the enzyme also exhibits in vitro 3alpha[17beta]-hydroxysteroid axidase activity with 3alpha-diol as the substrate | Homo sapiens | ? | - |
? | |
| 1.1.1.270 | 2 17beta-hydroxy-5alpha-androstan-3-one + 2 NADPH + 2 H+ | - |
Homo sapiens | 5alpha-androstane-3beta,17beta-diol + 5alpha-androstane-3alpha,17beta-diol + 2 NADP+ | the rates of 3alpha-diol versus 3beta-diol formation varies significantly among the isoforms. AKR1C1 predominantly catalyzes the formation of 3beta-diol, whereas AKR1C2 and AKR1C4 predominantly catalyze the formation of 3alpha-diol. AKR1C3 shows relatively low reductive activity towards 17beta-hydroxy-5alpha-androstan-3-one, in which 3alpha-diol and 3beta-diol is formed in almost equal amounts | ? | |
| 1.1.1.270 | 2 17beta-hydroxy-5alpha-androstan-3-one + 2 NADPH + 2 H+ | AKR1cs are a source of beta-tetrahydrosteroids. This is of physiological significance because the formation of 3beta-diol in contrast to 3alpha-diol is virtually irreversible, the 3beta-diol is a pro-apoptotic ligand for estrogen receptor beta, and 3beta-tetrahydrosteroids act as gamma-aminobutyric acid type A receptor antagonists | Homo sapiens | 5alpha-androstane-3beta,17beta-diol + 5alpha-androstane-3alpha,17beta-diol + 2 NADP+ | - |
? | |
| 1.1.1.270 | 3alpha-androstanediol + NAD+ | AKR1C2 and AKR1C4 act as 3alpha-hydroxysteroid oxidase, AKR1C3 predominantly acts as 17beta-hydroxysteroid oxidase catalyzing the conversion of 3alpha-diol to androsterone, negligible activity with the 3beta-androstanediol | Homo sapiens | ? + NADH | - |
? | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 1.1.1.50 | 3alpha-HSD | - |
Homo sapiens |
| 1.1.1.50 | 3alpha-hydroxysteroid dehydrogenase | - |
Homo sapiens |
| 1.1.1.50 | AKR1C | - |
Homo sapiens |
| 1.1.1.270 | AKR1Cs | - |
Homo sapiens |
Temperature Optimum [°C]
| EC Number | Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|---|
| 1.1.1.50 | 25 | - |
assay at | Homo sapiens |
Turnover Number [1/s]
| EC Number | Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|---|
| 1.1.1.50 | 0.0023 | - |
4-pregnen-3alpha,20beta-diol | pH 7.0, 25°C, isozyme AKR1C3 | Homo sapiens | |
| 1.1.1.50 | 0.0025 | - |
4-pregnen-3alpha,20beta-diol | pH 7.0, 25°C, isozyme AKR1C1 | Homo sapiens | |
| 1.1.1.50 | 0.046 | - |
4-pregnen-3alpha,20beta-diol | pH 7.0, 25°C, isozyme AKR1C2 | Homo sapiens | |
| 1.1.1.50 | 0.0735 | - |
4-pregnen-3alpha,20beta-diol | pH 7.0, 25°C, isozyme AKR1C4 | Homo sapiens | |
| 1.1.1.270 | 0.003 | - |
17beta-hydroxy-5alpha-androstan-3-one | pH 7.0, 37°C, radiometric analysis, formation of 3beta-androstanediol | Homo sapiens | |
| 1.1.1.270 | 0.0493 | - |
17beta-hydroxy-5alpha-androstan-3-one | pH 7.0, 37°C, radiometric analysis, formation of 3alpha-androstanediol | Homo sapiens | |
| 1.1.1.270 | 0.052 | - |
17beta-hydroxy-5alpha-androstan-3-one | pH 7.0, 37°C, spectrophotometric analysis, formation of 3beta-androstanediol or 3alpha-androstanediol | Homo sapiens | |
pH Optimum
| EC Number | pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|---|
| 1.1.1.50 | 7 | - |
assay at | Homo sapiens |
Cofactor
| EC Number | Cofactor | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.1.1.50 | NAD+ | - |
Homo sapiens | |
| 1.1.1.50 | NADP+ | - |
Homo sapiens | |
| 1.1.1.50 | NADPH | dependent on | Homo sapiens | |
| 1.1.1.270 | NADP+ | - |
Homo sapiens | |
| 1.1.1.270 | NADPH | - |
Homo sapiens | |
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