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Literature summary for 1.1.1.270 extracted from

  • Steckelbroeck, S.; Jin, Y.; Gopishetty, S.; Oyesanmi, B.; Penning, T.M.
    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.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
overexpression in Escherichia coli Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
Flufenamic acid inhibits 3alpha-diol versus 3beta-diol formation Homo sapiens
additional information NADPH-dependent 3-ketosteroid reductase activity is not inhibited by NAD+ Homo sapiens
NADPH potent inhibition of hydroxysteroid oxidase activity by low micromolar concentrations Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
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

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
Homo sapiens 5829
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
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

Organism UniProt Comment Textmining
Homo sapiens Q04828
-
-

Source Tissue

Source Tissue Comment Organism Textmining
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
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
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 ?
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+
-
?
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

Synonyms Comment Organism
AKR1Cs
-
Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.003
-
17beta-hydroxy-5alpha-androstan-3-one pH 7.0, 37°C, radiometric analysis, formation of 3beta-androstanediol Homo sapiens
0.0493
-
17beta-hydroxy-5alpha-androstan-3-one pH 7.0, 37°C, radiometric analysis, formation of 3alpha-androstanediol Homo sapiens
0.052
-
17beta-hydroxy-5alpha-androstan-3-one pH 7.0, 37°C, spectrophotometric analysis, formation of 3beta-androstanediol or 3alpha-androstanediol Homo sapiens

Cofactor

Cofactor Comment Organism Structure
NADP+
-
Homo sapiens
NADPH
-
Homo sapiens