Reaction participants Show >> << Hide
- Name help_outline 5α-androstan-3,11,17-trione Identifier CHEBI:34463 (CAS: 1482-70-8) help_outline Charge 0 Formula C19H26O3 InChIKeyhelp_outline VRHVOUYZPKSINF-XNTXBEAUSA-N SMILEShelp_outline C[C@]12CC(=O)[C@H]3[C@@H](CC[C@H]4CC(=O)CC[C@]34C)[C@@H]1CCC2=O 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADPH Identifier CHEBI:57783 (Beilstein: 10411862) help_outline Charge -4 Formula C21H26N7O17P3 InChIKeyhelp_outline ACFIXJIJDZMPPO-NNYOXOHSSA-J SMILEShelp_outline NC(=O)C1=CN(C=CC1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](OP([O-])([O-])=O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,365 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 10,232 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 17β-hydroxy-5α-androstan-3,11-dione Identifier CHEBI:234448 Charge 0 Formula C19H28O3 InChIKeyhelp_outline RSQKILYTRHKUIJ-HZGXJFKTSA-N SMILEShelp_outline [H]C12C(=O)CC3(C)C(O)CCC3([H])C2([H])CCC4([H])CC(=O)CCC14C 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADP+ Identifier CHEBI:58349 Charge -3 Formula C21H25N7O17P3 InChIKeyhelp_outline XJLXINKUBYWONI-NNYOXOHSSA-K SMILEShelp_outline NC(=O)c1ccc[n+](c1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](OP([O-])([O-])=O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,372 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:85531 | RHEA:85532 | RHEA:85533 | RHEA:85534 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Related reactions help_outline
More general form(s) of this reaction
Publications
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Human dehydrogenase/reductase SDR family member 11 (DHRS11) and aldo-keto reductase 1C isoforms in comparison: Substrate and reaction specificity in the reduction of 11-keto-C19-steroids.
Endo S., Morikawa Y., Kudo Y., Suenami K., Matsunaga T., Ikari A., Hara A.
Recent studies have shown that an adrenal steroid 11β-hydroxy-4-androstene-3,17-dione serves as the precursor to androgens, 11-ketotestosterone and 11-ketodihydrotestosterone (11KDHT). The biosynthetic pathways include the reduction of 3- and 17-keto groups of the androgen precursors 11-keto-C<sub ... >> More
Recent studies have shown that an adrenal steroid 11β-hydroxy-4-androstene-3,17-dione serves as the precursor to androgens, 11-ketotestosterone and 11-ketodihydrotestosterone (11KDHT). The biosynthetic pathways include the reduction of 3- and 17-keto groups of the androgen precursors 11-keto-C<sub>19</sub>-steroids, which has been reported to be mediated by three human enzymes; aldo-keto reductase (AKR)1C2, AKR1C3 and 17β-hydroxysteroid dehydrogenase (HSD) type-3. To explore the contribution of the enzymes in the reductive metabolism, we kinetically compared the substrate specificity for 11-keto-C<sub>19</sub>-steroids among purified recombinant preparations of four AKRs (1C1, 1C2,1C3 and 1C4) and DHRS11, which shows 17β-HSD activity. Although AKR1C1 did not reduce the 11-keto-C<sub>19</sub>-steroids, AKR1C3 and DHRS11 reduced 17-keto groups of 11-keto-4-androstene-3,17-dione, 11-keto-5α-androstane-3,17-dione (11K-Adione) and 11-ketoandrosterone with K<sub>m</sub> values of 5-28 μM. The 3-keto groups of 11KDHT and 11K-Adione were reduced by AKR1C4 (K<sub>m</sub> 1 μM) more efficiently than by AKR1C2 (K<sub>m</sub> 5 and 8 μM, respectively). GC/MS analysis of the products showed that DHRS11 acts as 17β-HSD, and that AKR1C2 and AKR1C4 are predominantly 3α-HSDs, but formed a minor 3β-metabolite from 11KDHT. Since DHRS11 was thus newly identified as 11-keto-C<sub>19</sub>-steroid reductase, we also investigated its substrate-binding mode by molecular docking and site-directed mutagenesis of Thr163 and Val200, and found the following structural features: 1). There is a space that accommodates the 11-keto group of the 11-keto-C<sub>19</sub>-steroids in the substrate-binding site. 2) Val200 is a critical determinant for exhibiting the strict 17β-HSD activity of the enzyme, because the Val200Leu mutation resulted in both significant impairment of the 17β-HSD activity and emergence of 3β-HSD activity towards 5α-androstanes including 11KDHT. << Less
J. Steroid Biochem. Mol. Biol. 199:105586-105586(2020) [PubMed] [EuropePMC]
This publication is cited by 6 other entries.