Showing papers on "Hydroxysteroid dehydrogenase published in 2018"
TL;DR: Analysis of the impact of 17β-HSD10 and its inhibitor, amyloid-β peptide (Aβ), on the metabolism of neuroactive steroids offers a new approach to AD pathogenesis.
Abstract: 17β-Hydroxysteroid dehydrogenase type 10 is a multifunctional, homotetrameric, mitochondrial protein encoded by the HSD17B10 gene at Xp 11.2. This protein, 17β-HSD10, is overexpressed in brain cells of Alzheimer's disease (AD) patients. It was reported to be involved in AD pathogenesis as the endoplasmic reticulum-associated amyloid-β binding protein (ERAB) and as amyloid-β binding alcohol dehydrogenase (ABAD). However, the exaggerated catalytic efficiencies for ERAB/ABAD in these reports necessitated the re-characterization of the catalytic functions of this brain enzyme. In addition to isoleucine metabolism, 17β-HSD10 is also responsible for the mitochondrial metabolism of neurosteroids such as 5α-androstane-3α,17β-diol and 17β-estradiol. These neurosteroids are inactivated by the oxidation catalyzed by 17β-HSD10. Since neurosteroid homeostasis is presumably essential for cognitive function, analysis of the impact of 17β-HSD10 and its inhibitor, amyloid-β peptide (Aβ), on the metabolism of neuroactive steroids offers a new approach to AD pathogenesis.
22 citations
TL;DR: A novel 3-oxoacyl-(acyl-carrier protein) (ACP) reductase was identified as it could bβ-estradiol, and was proved to be capable of functioning as 17β-HSD and played important role in its estrogen metabolism.
16 citations
TL;DR: Based on molecular modeling with docking experiments, two promising C3‐oxiranyl/xiranylmethyl‐estrane derivatives that would bind competitively and irreversibly in the catalytic site of 17&bgr;‐HSD1 are identified.
4 citations
TL;DR: In human embryonic kidney (HEK)-293 intact cells transfected with 17β-HSD10, only the steroidal inhibitor 1 induced a dose-dependent inhibition of E2 to E1 transformation, and biological assays showed that 1 and 2 inhibited the oxidation of estradiol (E2) into estrone (E1) by the 17 β- HSD10 recombinant protein.
Abstract: 17β-Hydroxysteroid dehydrogenase type 10 (17β-HSD10) is a steroidogenesis enzyme known for its potential role in Alzheimer’s disease For comparison purposes between steroidal and nonsteroidal 17β-HSD10 inhibitors 1 and 2, respectively, we attempted the chemical synthesis of benzothiazole phosphonate derivative 2 Instead of a one-pot synthesis, we report a two-step synthesis with characterization of both imine intermediate 5 and final compound 2 Furthermore, complete assignation of 1H and 13C nuclear magnetic resonance (NMR) signals of 2 is provided, as we observed a divergence of NMR data with those published previously Finally, biological assays showed that 1 and 2 inhibited the oxidation of estradiol (E2) into estrone (E1) by the 17β-HSD10 recombinant protein However, in human embryonic kidney (HEK)-293 intact cells transfected with 17β-HSD10, only the steroidal inhibitor 1 induced a dose-dependent inhibition of E2 to E1 transformation
4 citations
Patent•
15 May 2018
TL;DR: The 7 alpha-hydroxysteroid dehydrogenase (7 alpha-HSDH) as mentioned in this paper can catalyze asubstrate taurocholic acid to generate taurine 7-ketone cholic acid (T7K-CA), catalyze a substrate GCA to generate GCA, and catalyzes a substrate EB to generate ethyl 2-hydroxyl-2-phenylacetate.
Abstract: The invention discloses 7 alpha-hydroxysteroid dehydrogenase as well as a coding gene and application thereof. An amino acid sequence of the 7 alpha-hydroxysteroid dehydrogenase provided by the invention is shown as SEQ ID NO. 1, and a nucleotide sequence of the 7 alpha-hydroxysteroid dehydrogenase gene is disclosed and shown as SEQ ID NO. 2. The 7 alpha-hydroxysteroid dehydrogenase can catalyze asubstrate taurocholic acid (TCA) to generate taurine 7-ketone cholic acid (T7K-CA), catalyze a substrate glycocholic acid (GCA) to generate glycine 7-ketone cholic acid (G7K-CA), catalyze a substratetaurochenodeoxycholic acid (TCDCA) to generate taurine 7-ketone lithocholic acid (T7K-LCA), catalyze a substrate glycochenodeoxycholic acid (GCDCA) to generate glycine 7-ketone lithocholic acid (G7K-LCA) and catalyze a substrate ethyl benzoylformate (EB) to generate ethyl 2-hydroxy-2-phenylacetate, and has better catalytic activity, has a catalytic activity to TCDCA, GCDCA and EB 10, 5, and 3 times that of sardinia clostridium 7 alpha-HSDH, correspondingly, and has great industrial application value.
3 citations
Patent•
25 Dec 2018
TL;DR: In this article, a 3 alpha-hydroxysteroid dehydrogenase (HSD) mutant was obtained by subjecting amino acid sequence as shown in SEQ ID No. 2 to point mutation, wherein the point mutation is the amino acid substitution of at least one locus selected from the 25th-37th sites, the 100th-120ths sites and the 145th-166th sites.
Abstract: The invention provides a 3alpha-hydroxysteroid dehydrogenase mutant, nucleotide sequence for coding the 3alpha-hydroxysteroid dehydrogenase mutant and a kit. The 3alpha-HSD mutant is obtained by subjecting amino acid sequence as shown in SEQ ID No. 2 to point mutation, wherein the point mutation is the amino acid substitution of at least one locus selected from the 25th-37th sites, the 100th-120thsites and the 145th-166th sites. By the point mutation, 3alpha-hydroxysteroid dehydrogenase mutant protease with high catalytic activity is obtained, enzyme catalytic activity can be evidently increased by more than 60% as compared with 3alpha-HSD, and the enzyme catalytic activity can reach up to twice of the original enzyme catalytic activity; by using the mutant protease as the tool enzyme, the total bile acid content and enzymatic method detection efficiency of the kit are improved greatly, production cost is lowered, and the market competiveness of corresponding products is increased.
2 citations