Cloned (Comment) | Organism |
---|---|
gene Akr1c9, recombinant expression in COS-1 cells | Rattus norvegicus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
apigenin | about 90% inhibition at 0.1 mM, inhibition kinetics. Apigenin inhibits AKR1C9 in a mixed-type inhibitory mode when the cofactor is used. This indicates that apigenin also affects the cofactor-binding site besides its binding to the active site of the steroid substrate. Docking analysis of the binding of apigenin to rat AKR1C9 with bound NADPH and substrate dihydrotestsosterone | Rattus norvegicus |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
0.00342 | - |
dihydrotestosterone | pH 7.2, 37°C, recombinant enzyme | Rattus norvegicus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | - |
Rattus norvegicus | 5829 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
dihydroprogesterone + NADPH + H+ | Rattus norvegicus | - |
allopregnanolone + NADP+ | - |
? | |
dihydrotestosterone + NADPH + H+ | Rattus norvegicus | - |
5alpha-androstane-3alpha,17beta-diol + NADP+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Rattus norvegicus | P23457 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant enzyme from cytosol of COS-1 cells by ultracentrifugation | Rattus norvegicus |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
brain | - |
Rattus norvegicus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
dihydroprogesterone + NADPH + H+ | - |
Rattus norvegicus | allopregnanolone + NADP+ | - |
? | |
dihydrotestosterone + NADPH + H+ | - |
Rattus norvegicus | 5alpha-androstane-3alpha,17beta-diol + NADP+ | - |
? |
Synonyms | Comment | Organism |
---|---|---|
3alpha-hydroxysteroid dehydrogenase | - |
Rattus norvegicus |
AKR1C9 | - |
Rattus norvegicus |
NADPH-dependent AKR1C9 | - |
Rattus norvegicus |
type I 3alpha-HSD | - |
Rattus norvegicus |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Rattus norvegicus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.2 | - |
assay at | Rattus norvegicus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADPH | - |
Rattus norvegicus |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.891 | - |
pH 7.2, 37°C, recombinant enzyme | Rattus norvegicus | apigenin |
General Information | Comment | Organism |
---|---|---|
metabolism | the synthesis of allopregnanolone (ALLO) and 5alpha-androstane-3alpha,17beta-diol (DIOL) needs 5alpha-reductase 1 (SRD5A1) and 3alpha-hydroxysteroid dehydrogenase (AKR1C9). SRD5A1 is a microsomal NADPH-dependent enzyme, which metabolizes progesterone into dihydroprogesterone or testosterone into dihydrotestosterone (DHT). Subsequently, cytosolic NADPH-dependent AKR1C9 metabolizes the above steroid intermediates into ALLO and DIOL, respectively. Another microsomal NAD+-dependent retinol dehydrogenase 2 (RoDH2, EC 1.1.1.53) catalyzes the opposite direction of AKR1C9. Thus, the levels of ALLO and DIOL also depend on the activity of RoDH2. These three enzymes have been shown to be present in the brain | Rattus norvegicus |
additional information | AKR1C9 has two substrate binding sites, the steroid binding site and the cofactor binding site | Rattus norvegicus |
physiological function | the cytosolic NADPH-dependent AKR1C9 metabolizes the steroid intermediates dihydroprogesterone and dihydrotestosterone into allopregnanolone (ALLO) and 5alpha-androstane-3alpha,17beta-diol (DIOL), respectively | Rattus norvegicus |