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Literature summary extracted from

  • Wu, Y.; Li, L.; Zhou, S.; Shen, Q.; Lin, H.; Zhu, Q.; Sun, J.; Ge, R.S.
    Apigenin inhibits rat neurosteroidogenic 5alpha-reductase 1 and 3alpha-hydroxysteroid dehydrogenase (2017), Neurochem. Int., 110, 84-90 .
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.1.1.50 expression in Cos-1 cells Rattus norvegicus
1.1.1.53 expression in Cos-1 cells Rattus norvegicus
1.1.1.357 gene Akr1c9, recombinant expression in COS-1 cells Rattus norvegicus
1.3.1.22 expression in Cos-1 cells Rattus norvegicus

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.1.1.50 apigenin competitive inhibition with the substrate 5alpha-dihydrotestosterone, uncompetitively inhibition with the cofactor NADPH. Significantly inhibits rat AKR1C9 at 0.1 mM; competitive inhibition with the substrate 5alpha-dihydrotestosterone, uncompetitively inhibition with the cofactor NADPH. Significantly inhibits rat AKR1C9 at 0.1 mM. Apigenin is a potent inhibitor of rat AKR1C9, thereby controlling the rate of neurosteroid biosynthesis Rattus norvegicus
1.1.1.53 apigenin significant inhibition at 0.1 mM Rattus norvegicus
1.1.1.357 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
1.3.1.22 apigenin
-
 Rattus norvegicus

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.1.1.50 0.003415
-
 5alpha-dihydrotestosterone 37°C, pH 7.2 Rattus norvegicus
1.1.1.53 0.00317
-
 5alpha-dihydrotestosterone 37°C, pH 7.2 Rattus norvegicus
1.1.1.357 0.00342
-
 dihydrotestosterone pH 7.2, 37°C, recombinant enzyme Rattus norvegicus
1.3.1.22 0.001568
-
 testosterone 37°C, pH not specified in the publication Rattus norvegicus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.1.1.50 cytosol
-
 Rattus norvegicus 5829
-
1.1.1.53 cytosol
-
 Rattus norvegicus 5829
-
1.1.1.357 cytosol
-
 Rattus norvegicus 5829
-
1.3.1.22 microsome
-
 Rattus norvegicus
-
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.1.1.50 5alpha-dihydrotestosterone + NADPH + H+ Rattus norvegicus
-
 5alpha-androstan-3alpha,17beta-diol + NADP+
-
 ?
1.1.1.357 dihydroprogesterone + NADPH + H+ Rattus norvegicus
-
 allopregnanolone + NADP+
-
 ?
1.1.1.357 dihydrotestosterone + NADPH + H+ Rattus norvegicus
-
 5alpha-androstane-3alpha,17beta-diol + NADP+
-
 ?
1.3.1.22 testosterone + NADPH + H+ Rattus norvegicus
-
 dihydrotestosterone + NADP+
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.1.1.50 Rattus norvegicus P23457
-
-
1.1.1.53 Rattus norvegicus P50170
-
-
1.1.1.357 Rattus norvegicus P23457
-
-
1.3.1.22 Rattus norvegicus P24008
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.1.1.357 recombinant enzyme from cytosol of COS-1 cells by ultracentrifugation Rattus norvegicus

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.1.1.357 brain
-
 Rattus norvegicus
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.1.1.50 5alpha-dihydrotestosterone + NADPH + H+
-
 Rattus norvegicus 5alpha-androstan-3alpha,17beta-diol + NADP+
-
 ?
1.1.1.53 5alpha-dihydrotestosterone + NADPH
-
 Rattus norvegicus 5alpha-androstan-3alpha,17beta-diol + NAD+
-
 ?
1.1.1.357 dihydroprogesterone + NADPH + H+
-
 Rattus norvegicus allopregnanolone + NADP+
-
 ?
1.1.1.357 dihydrotestosterone + NADPH + H+
-
 Rattus norvegicus 5alpha-androstane-3alpha,17beta-diol + NADP+
-
 ?
1.3.1.22 testosterone + NADPH + H+
-
 Rattus norvegicus dihydrotestosterone + NADP+
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.1.1.50 3alpha-hydroxysteroid dehydrogenase
-
 Rattus norvegicus
1.1.1.50 AKR1C9
-
 Rattus norvegicus
1.1.1.53 retinol dehydrogenase 2
-
 Rattus norvegicus
1.1.1.53 RoDH2
-
 Rattus norvegicus
1.1.1.357 3alpha-hydroxysteroid dehydrogenase
-
 Rattus norvegicus
1.1.1.357 AKR1C9
-
 Rattus norvegicus
1.1.1.357 NADPH-dependent AKR1C9
-
 Rattus norvegicus
1.1.1.357 type I 3alpha-HSD
-
 Rattus norvegicus
1.3.1.22 neurosteroidogenic 5alpha-reductase 1
-
 Rattus norvegicus
1.3.1.22 SRD5A1
-
 Rattus norvegicus

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.1.1.357 37
-
 assay at Rattus norvegicus

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.1.1.357 7.2
-
 assay at Rattus norvegicus

Cofactor

EC Number Cofactor Comment Organism Structure
1.1.1.357 NADPH
-
 Rattus norvegicus

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.1.1.50 0.000891
-
 37°C, pH 7.2 Rattus norvegicus apigenin
1.1.1.357 0.891
-
 pH 7.2, 37°C, recombinant enzyme Rattus norvegicus apigenin
1.3.1.22 0.1
-
 37°C, pH not specified in the publication Rattus norvegicus apigenin

General Information

EC Number General Information Comment Organism
1.1.1.357 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
1.1.1.357 additional information AKR1C9 has two substrate binding sites, the steroid binding site and the cofactor binding site Rattus norvegicus
1.1.1.357 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