EC Number   |
General Information |
Reference |
|---|
    1.1.1.64 | physiological function |
exposure of HCT-15 cells to cisplatin results in aquisition of cisplatin resistance and concomitant induction of isoform AKR1C3 and aldo-keto reductase AKR1C1 expression. The resistance lowers the sensitivity toward cellular damages evoked by oxidative stress-derived aldehydes, 4-hydroxy-2-nonenal and 4-oxo-2-nonenal that are detoxified by AKR1C1 and AKR1C3. Overexpression of AKR1C1 or AKR1C3 in the parental HCT15 cells mitigates the cytotoxicity of the aldehydes and cisplatin. Knockdown of both AKR1C1 and AKR1C3 in the resistant cells or treatment of the cells with specific inhibitors of the aldo-keto reductases increases the sensitivity to ciplatin toxicity |
724719 |
| 1.1.1.64 | physiological function |
in LNCaP and LNCaP-AKR1C3 cells overexpressing isoform AKR1C3, metabolism proceeds via 5alpha-reduction to form 5alpha-androstane-3,17-dione and then (epi)androsterone-3-glucuronide. LNCaP-AKR1C3 cells make significantly higher amounts of testosterone-17beta-glucuronide. When 5alpha-reductase is inhibited by finasteride, the production of testosterone-17beta-glucuronide is further elevated in LNCaP-AKR1C3 cells. When AKR1C3 activity is inhibited with indomethacin the production of testosterone-17beta-glucuronide is significantly decreased. 4-Androstene-3,17-dione treatment stimulates cell proliferation in both cell lines. LNCaP-AKR1C3 cells are resistant to the growth inhibitory properties of finasteride, consistent with the diversion of 4-androstene-3,17-dione metabolism from 5alpha-reduced androgens to increased formation of testosterone |
725825 |
| 1.1.1.64 | physiological function |
isoform 17beta-HSD3-dependent reduction of 4-androstene-3,17-dione is affected by neither coexpression with 11beta-HSD1, EC 1.1.1.146, nor overexpression or knock-down of hexose-6-phosphate dehydrogenase. Knock-down of glucose-6-phosphate dehydrogenase decreases 17beta-HSD3 activity, indicating dependence on cytoplasmic NADPH. Cytoplasmic orientation of isoform 17beta-HSD3 and dependence on glucose-6-phosphate dehydrogenase-generated NADPH explain the lack of a direct functional coupling with the luminal 11beta-HSD1-mediated glucocorticoid metabolism |
724850 |
| 1.1.1.64 | physiological function |
the enzyme (HSD17B3) contributes to development of male sexual characteristics by converting androstenedione (A4) to testosterone |
761760 |
| 1.1.1.64 | physiological function |
the two reactions 11beta-HSD1-dehydrogenase, EC 1.1.1.146, and 17beta-HSD3, EC 1.1.1.64, which utilize NADPH are competing for NADPH from the same cofactor pool. 11beta-HSD1-dehydrogenase serves as a NADPH-regenerating system that is tightly coupled in regulating 17beta-HSD3 reaction synthesizing testosterone. A cycle can exist whereby the NADPH produced by 11beta-HSD1 dehydrogenase can drive the reductase activity of 17beta-HSD3 and the NADP+ produced by 17beta-HSD3 and other enzymes involved in testosterone biosynthesis can drive the dehydrogenase activity of 11beta-HSD1 |
726493 |
