Dehydrolithocholic Acid
(Synonyms: 3-Ketolithocholic Acid) 目录号 : GC47182A major metabolite of lithocholic acid
Cas No.:1553-56-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Dehydrolithocholic acid is a major metabolite of lithocholic acid .[1] It is formed from LCA by the cytochrome P450 (CYP) isoform CYP3A4. Dehydrolithocholic acid is an agonist of G protein-coupled bile acid activated receptor 1 (GP-BAR1/TGR5; EC50 = 0.27 μM), vitamin D receptor (VDR; EC50 = 3 μM), and farnesoid X receptor (FXR) in cell-based reporter assays.[2],[3] It also binds to the human pregnane X receptor (PXR; IC50 = 15 μM) and activates mouse and human PXRs in cell-based reporter assays when used at a concentration of 100 μM.[4] Dehydrolithocholic acid binds to retinoic acid receptor-related orphan receptor γt (RORγt; Kd = 1.13 μM for the recombinant human ligand-binding domain) and decreases its activity in a cell-based reporter assay when used at a concentration of 10 μM.[5] It inhibits the differentiation of T helper cells that express IL-17a (TH17 cells) when used at a concentration of 20 μM.
Reference:
[1].Deo, A.K., and Bandiera, S.M.3-Ketocholanoic acid is the major in vitro human hepatic microsomal metabolite of lithocholic acidDrug Metab. Dispos.37(9)1938-1947(2009)
[2].Sato, H., Macchiarulo, A., Thomas, C., et al.Novel potent and selective bile acid derivatives as TGR5 agonists: Biological screening, structure-activity relationships, and molecular modeling studiesJ. Med. Chem.51(6)1831-1841(2008)
[3].Makishima, M., Lu, T.T., Xie, W., et al.Vitamin D receptor as an intestinal bile acid sensorScience296(5571)1313-1316(2002)
[4].Staudinger, J.L., Goodwin, B., Jones, S.A., et al.The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicityProc. Natl. Acad. Sci. USA98(6)3369-3374(2000)
[5].Hang, S., Paik, D., Yao, L., et al.Bile acid metabolites control TH17 and Treg cell differentiationNature576(7785)143-148(2019)
| Cas No. | 1553-56-6 | SDF | |
| 别名 | 3-Ketolithocholic Acid | ||
| 化学名 | (5β)-3-oxo-cholan-24-oic acid | ||
| Canonical SMILES | C[C@H](CCC(O)=O)[C@@]1([H])CC[C@@]2([H])[C@]3([H])CC[C@]4([H])CC(CC[C@]4(C)[C@@]3([H])CC[C@@]21C)=O | ||
| 分子式 | C24H38O3 | 分子量 | 374.6 |
| 溶解度 | DMF: 30 mg/ml,DMF:PBS (pH 7.2) (1:4): 0.20 mg/ml,DMSO: 15 mg/ml,Ethanol: 10 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6695 mL | 13.3476 mL | 26.6951 mL |
| 5 mM | 0.5339 mL | 2.6695 mL | 5.339 mL |
| 10 mM | 0.267 mL | 1.3348 mL | 2.6695 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Metabolism of chenodeoxycholic acid in hamsters
Lipids 1976 Dec;11(12):845-7.PMID:1011939DOI:10.1007/BF02532990.
The study on the metabolism after oral administration of chenodeoxycholic acid-24-14C was performed by analysis of radioactivity that had appeared in bile and feces of male hamsters. The radioactive bile acids were analyzed by thin layer chromatography and identified by the isotope dilution method. In the bile of the hamsters with bile fistula, radioactivity was originated from unchanged chenodeoxycholic acid for the most part, and 7-ketolithocholic acid, lithocholic acid, and beta-muricholic acid for the remainder. In the feces lithocholic acid, Dehydrolithocholic Acid, isolithocholic acid, and unchanged form were identified. After the multiple dosing of chenodeoxycholic acid-24-14C for 6 days, beta-muricholic acid was also identified in the feces.
Intrauterine growth retardation affects liver bile acid metabolism in growing pigs: effects associated with the changes of colonic bile acid derivatives
J Anim Sci Biotechnol 2022 Nov 2;13(1):117.PMID:36320049DOI:10.1186/s40104-022-00772-6.
Background: Intrauterine growth retardation (IUGR) is associated with severely impaired nutrient metabolism and intestinal development of pigs. Our previous study found that IUGR altered intestinal microbiota and metabolites in the colon. However, the consequences of IUGR on bile acid metabolism in pigs remained unclear. The present study aimed to investigate the bile acid metabolism in the liver and the profile of bile acid derivatives in the colon of growing pigs with IUGR using bile acid targeted metabolomics. Furthermore, we determined correlations between colonic microbiota composition and metabolites of IUGR and normal birth weight (NBW) pigs at different growth stages that were 7, 21, and 28-day-old, and the average body weight (BW) of 25, 50, and 100 kg of the NBW pigs. Results: The results showed that the plasma total bile acid concentration was higher (P < 0.05) at the 25 kg BW stage and tended to increase (P = 0.08) at 28-day-old in IUGR pigs. The hepatic gene expressions related to bile acid synthesis (CYP7A1, CYP27A1, and NTCP) were up-regulated (P < 0.05), and the genes related to glucose and lipid metabolism (ATGL, HSL, and PC) were down-regulated (P < 0.05) at the 25 kg BW stage in IUGR pigs when compared with the NBW group. Targeted metabolomics analysis showed that 29 bile acids and related compounds were detected in the colon of pigs. The colonic concentrations of Dehydrolithocholic Acid and apocholic acid were increased (P < 0.05), while isodeoxycholic acid and 6,7-diketolithocholic acid were decreased (P < 0.05) in IUGR pigs, when compared with the NBW pigs at the 25 kg BW stage. Moreover, Spearman's correlation analysis revealed that colonic Unclassified_[Mogibacteriaceae], Lachnospira, and Slackia abundances were negatively correlated (P < 0.05) with Dehydrolithocholic Acid, as well as the Unclassified_Clostridiaceae abundance with 6,7-diketolithocholic acid at the 25 kg BW stage. Conclusions: These findings suggest that IUGR could affect bile acid and glucolipid metabolism in growing pigs, especially at the 25 kg BW stage, these effects being paralleled by a modification of bile acid derivatives concentrations in the colonic content. The plausible links between these modified parameters are discussed.
Enhancement of anti-inflammatory effect of cattle bile by fermentation and its inhibition of neuroinflammation on microglia by inhibiting NLRP3 inflammasome
J Biosci Bioeng 2022 Feb;133(2):146-154.PMID:34887181DOI:10.1016/j.jbiosc.2021.11.003.
As a kind of animal medicine, cattle bile has anti-inflammatory, antipyretic and cholagogic effects. The fermentation process of cattle bile is included in the application of many traditional Chinese medicines. In this study, we fermented cattle bile singly and investigated the impact of fermentation on the anti-inflammatory effect of cattle bile, as well as the mechanism of fermented cattle bile on microglia cells. After high temperature sterilization, cattle bile was fermented with Massa Medicata Fermentata (medicated leaven, Shen Qu). We used ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS) to analyze the bile acids of cattle bile and fermented cattle bile. The results showed that 3-dehydrocholic acid, 7-ketolithocholic acid, 12-dehydrocholic acid, 12-Ketolithocholic acid, ursodeoxycholic acid and Dehydrolithocholic Acid increased more significantly than others; glycocholic acid and glycochenodeoxycholic acid decreased more significantly than others. After fermentation, cattle bile significantly reduced the release of NO and inflammatory factors (TNF-α and IL-1β). Furthermore, the protein expression of TNF-α, IL-1β and iNOS were decreased. In addition, we found that fermented cattle bile could have an anti-inflammatory effect through attenuating the activation of NLRP3 inflammasome. Thus, fermentation can enhance the anti-inflammatory effect of cattle bile. Fermented cattle bile has an anti-inflammatory effect by inhibiting the NLRP3 inflammasome pathway, which can expand the clinical application of cattle bile and provide new thoughts and methods for the application of cattle bile.
Stereoselective reversible ketone formation from 10-hydroxylated nortriptyline metabolites in human liver
Xenobiotica 1995 Dec;25(12):1311-25.PMID:8719907DOI:10.3109/00498259509061920.
1. E- and Z-10-hydroxynortriptyline are major metabolites of amitriptyline and nortriptyline in man. Upon incubation with human liver microsomes or cytosol, these metabolites were oxidized to the corresponding ketones, E- and Z-10-oxonortriptyline. (+)-E- and (+)-Z-10-hydroxynortriptyline were distinctly preferred over the (-)-isomers as substrates. NADP+ supported the oxidation in cytosol, whereas in microsomes NAD+ was the best cofactor. 2. Incubation of E- and Z-10-oxonortriptyline with NADPH and cytosol resulted in the nearly exclusive formation of (+)-E- and (+)-Z-10-hydroxynortriptyline. Kinetic analysis revealed high-affinity reduction (K(m) 1-2 microM) of the two ketones and an additional low-affinity component with the E-isomer. 10-Oxonortriptyline reduction was also catalysed by rabbit, but not by rat or guinea pig liver cytosol. 3. With [4-3H]NADPH as cosubstrate, tritium was incorporated into E- and Z-10-hydroxynortriptyline preferentially from the pro-4R position. Redox cycling of (+)-E- and (+)-Z-10-hydroxynortriptyline in cytosol in the presence of NAD- and NADPH was indicated by 3H incorporation from [pro-4R-3H]NADPH. 4. Recombinant human carbonyl reductase catalysed low-affinity reduction of E-10-oxonortriptyline with preferential transfer of the pro-4S-3H of labelled NADPH. 5. Ketone reduction in cytosol was strongly inhibited by 9,10-phenanthrenequinone and Dehydrolithocholic Acid and moderately by other 3-oxo steroids and some anti-inflammatory drugs. 6. The high-affinity reduction of E- and Z-10-oxonortriptyline and the oxidation of the alcohols in cytosol are probably mediated by a member of the aldo-keto reductase family of enzymes.
Structural and functional comparison of two human liver dihydrodiol dehydrogenases associated with 3 alpha-hydroxysteroid dehydrogenase activity
Biochem J 1992 Mar 15;282 ( Pt 3)(Pt 3):741-6.PMID:1554355DOI:10.1042/bj2820741.
Two monomeric dihydrodiol dehydrogenases with pI values of 5.4 and 7.6 were co-purified with androsterone dehydrogenase activity to homogeneity from human liver. The two enzymes differed from each other on peptide mapping and in their heat-stabilities; with respect to the latter the dihydrodiol dehydrogenase and 3 alpha-hydroxysteroid dehydrogenase activities of the respective enzymes were similarly inactivated. The pI 5.4 enzyme was equally active towards trans- and cis-benzene dihydrodiols, and towards (S)- and (R)-forms of indan-1-ol and 1,2,3,4-tetrahydronaphth-1-ol and oxidized the 3 alpha-hydroxy group of C19-, C21- and C24-steroids, whereas the pI 7.6 enzyme showed high specificity for trans-benzene dihydrodiol, (S)-forms of the alicyclic alcohols and C19- and C21-steroids. Although the two enzymes reduced various xenobiotic carbonyl compounds and the 3-oxo group of C19- and C21-steroids, and were A-specific in the hydrogen transfer from NADPH, only the pI 5.4 enzyme showed reductase activity towards 7 alpha-hydroxy-5 beta-cholestan-3-one and Dehydrolithocholic Acid. The affinity of the two enzymes for the steroidal substrates was higher than that for the xenobiotic substrates. The two enzymes also showed different susceptibilities to the inhibition by anti-inflammatory drugs and bile acids. Whereas the pI-5.4 enzyme was highly sensitive to anti-inflammatory steroids, showing mixed-type inhibitions with respect to indan-1-ol and androsterone, the pI 7.6 enzyme was inhibited more potently by non-steroidal anti-inflammatory drugs and bile acids than by the steroidal drugs, and the inhibitions were all competitive. These structural and functional differences suggest that the two enzymes are 3 alpha-hydroxysteroid dehydrogenase isoenzymes.