Literature summary for 1.1.1.357 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 .

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Cloned(Commentary)

Cloned (Comment)	Organism
gene Akr1c9, recombinant expression in COS-1 cells	Rattus norvegicus

Inhibitors

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 [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
0.00342	-	dihydrotestosterone	pH 7.2, 37°C, recombinant enzyme	Rattus norvegicus

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytosol	-	Rattus norvegicus	5829	-

Natural Substrates/ Products (Substrates)

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

Organism	UniProt	Comment	Textmining
Rattus norvegicus	P23457	-	-

Purification (Commentary)

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

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	-	Rattus norvegicus	-

Substrates and Products (Substrate)

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

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

pH Optimum

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

Cofactor

Cofactor	Comment	Organism	Structure
NADPH	-	Rattus norvegicus

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.891	-	pH 7.2, 37°C, recombinant enzyme	Rattus norvegicus	apigenin

General Information

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

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Release 2023.1 (January 2023)