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Literature summary extracted from
- 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 (2006), J. Pharmacol. Exp. Ther., 316, 1300-1309.
Cloned(Commentary)
| EC Number | Cloned (Comment) | Organism |
|---|---|---|
| 1.1.1.270 | quantitative expression analysis of AKR1C isozymes | Homo sapiens |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.1.1.50 | Flufenamic acid | a nonsteroidalanti-inflammatory drug, IC50: 1.084 mM | Homo sapiens |  |
| 1.1.1.50 | additional information | no inhibition by the bile acid 5beta-cholanic acid-3alpha,7alpha-diol | Homo sapiens | |
| 1.1.1.50 | Phenolphthalein | AKR1C4-selective inhibitor, in vitro and in vivo inhibition, IC50: 0.0004 mM | Homo sapiens | |
| 1.1.1.213 | Flufenamic acid | a nonsteroidalanti-inflammatory drug, IC50: 1.084 mM | Homo sapiens | |
| 1.1.1.213 | additional information | no inhibition by the bile acid 5beta-cholanic acid-3alpha,7alpha-diol | Homo sapiens | |
| 1.1.1.213 | Phenolphthalein | AKR1C4-selective inhibitor, in vitro and in vivo inhibition, IC50: 0.0004 mM | Homo sapiens | |
| 1.1.1.270 | 5beta-cholanic acid-3alpha,7alpha-diol | - |
Homo sapiens | |
| 1.1.1.270 | Flufenamic acid | in vitro and in vivo inhibition of AKR1C1 | Homo sapiens | |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 1.1.1.50 | cytosol | - |
Homo sapiens | 5829 | - |
| 1.1.1.50 | additional information | subcellular localization study, overview | Homo sapiens | - |
- |
| 1.1.1.213 | cytosol | - |
Homo sapiens | 5829 | - |
| 1.1.1.213 | additional information | subcellular localization study, overview | Homo sapiens | - |
- |
| 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 | tibolone + NADPH + H+ | 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 | 3-hydroxytibolone + NADP+ | - |
? | |
| 1.1.1.213 | tibolone + NADPH + H+ | 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 | 3-hydroxytibolone + NADP+ | - |
? | |
| 1.1.1.270 | 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
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 1.1.1.50 | Homo sapiens | - |
- |
- |
| 1.1.1.213 | Homo sapiens | - |
- |
- |
| 1.1.1.270 | Homo sapiens | - |
isozymes AKR1C1 and AKR1C2 | - |
Source Tissue
| EC Number | Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|---|
| 1.1.1.50 | hepatocyte | primary, high expression and activity in healthy hepatocytes | Homo sapiens | - |
| 1.1.1.50 | liver | high expression and activity in female and male liver | Homo sapiens | - |
| 1.1.1.50 | additional information | no activity in the hepatoma cell line Hep-G2 | Homo sapiens | - |
| 1.1.1.213 | hepatocyte | primary, high expression and activity in healthy hepatocytes | Homo sapiens | - |
| 1.1.1.213 | liver | high expression and activity in female and male liver | Homo sapiens | - |
| 1.1.1.213 | additional information | no activity in the hepatoma cell line Hep-G2 | Homo sapiens | - |
| 1.1.1.270 | Hep-G2 cell | - |
Homo sapiens | - |
| 1.1.1.270 | hepatocyte | primary, time-dependent reduction of tibolone into 3beta- and 3alpha-hydroxytibolone was observed again in a 4:1 ratio | Homo sapiens | - |
| 1.1.1.270 | liver | - |
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 | additional information | - |
- |
Homo sapiens |
| 1.1.1.213 | additional information | - |
- |
Homo sapiens |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.1.1.50 | tibolone + NADPH + H+ | 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 | Homo sapiens | 3-hydroxytibolone + NADP+ | - |
? | |
| 1.1.1.50 | tibolone + NADPH + H+ | i.e. [7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, stereoselctive reaction to the 3alpha-hydroxytibolone product | Homo sapiens | 3-hydroxytibolone + NADP+ | - |
? | |
| 1.1.1.50 | tibolone + NADPH + H+ | i.e. [7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, stereoselective reaction to the 3alpha-hydroxytibolone product | Homo sapiens | 3-hydroxytibolone + NADP+ | - |
? | |
| 1.1.1.213 | tibolone + NADPH + H+ | 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 | Homo sapiens | 3-hydroxytibolone + NADP+ | - |
? | |
| 1.1.1.213 | tibolone + NADPH + H+ | i.e. [7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, stereoselctive reaction to the 3alpha-hydroxytibolone product | Homo sapiens | 3-hydroxytibolone + NADP+ | - |
? | |
| 1.1.1.270 | 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 | Homo sapiens | ? | - |
? | |
| 1.1.1.270 | additional information | comparison of substrate specificity and enantioselectivity of AKR1C isozymes, overview | Homo sapiens | ? | - |
? | |
| 1.1.1.270 | [7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one + NADPH | i.e. tibolone, a synthetic hormone | Homo sapiens | [7alpha,17alpha]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-ol + NADP+ | reaction product determination and analysis | ? | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 1.1.1.50 | AKR1C4 | - |
Homo sapiens |
| 1.1.1.50 | More | cf. 1.1.1.213, the enzyme belongs to the aldo-keto reductase subfamily AKR1C | Homo sapiens |
| 1.1.1.50 | More | cf. EC 1.1.1.213, the enzyme belongs to the aldo-keto reductase subfamily AKR1C | Homo sapiens |
| 1.1.1.213 | AKR1C4 | - |
Homo sapiens |
| 1.1.1.213 | More | cf. EC 1.1.1.50, the enzyme belongs to the aldo-keto reductase subfamily AKR1C | Homo sapiens |
| 1.1.1.270 | 3-ketosteroid reductase | - |
Homo sapiens |
| 1.1.1.270 | 3beta-hydroxysteroid dehydrogenase | - |
Homo sapiens |
| 1.1.1.270 | AKR1C1 | - |
Homo sapiens |
| 1.1.1.270 | AKR1C2 | - |
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 |
| 1.1.1.213 | 25 | - |
assay at | Homo sapiens |
| 1.1.1.270 | 37 | - |
assay at | Homo sapiens |
pH Optimum
| EC Number | pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|---|
| 1.1.1.50 | 7 | - |
assay at | Homo sapiens |
| 1.1.1.213 | 7 | - |
assay at | Homo sapiens |
| 1.1.1.270 | 7.4 | - |
assay at | Homo sapiens |
Cofactor
| EC Number | Cofactor | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.1.1.50 | NADPH | - |
Homo sapiens | |
| 1.1.1.213 | NADPH | - |
Homo sapiens | |
| 1.1.1.270 | NADPH | - |
Homo sapiens | |
IC50 Value
| EC Number | IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|---|
| 1.1.1.50 | 0.0004 | - |
AKR1C4-selective inhibitor, in vitro and in vivo inhibition, IC50: 0.0004 mM | Homo sapiens | Phenolphthalein | |
| 1.1.1.50 | 1.084 | - |
a nonsteroidalanti-inflammatory drug, IC50: 1.084 mM | Homo sapiens | Flufenamic acid | |
| 1.1.1.213 | 0.0004 | - |
AKR1C4-selective inhibitor, in vitro and in vivo inhibition, IC50: 0.0004 mM | Homo sapiens | Phenolphthalein | |
| 1.1.1.213 | 1.084 | - |
a nonsteroidalanti-inflammatory drug, IC50: 1.084 mM | Homo sapiens | Flufenamic acid | |
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