Isolithocholic Acid
(Synonyms: 异石胆酸,isoLCA) 目录号 : GC47466A bile acid
Cas No.:1534-35-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Isolithocholic acid is a bile acid that is formed via microbial metabolism of lithocholic acid or lithocholic acid 3α-sulfate .[1],[2] Isolithocholic acid (0.01%) inhibits spore germination induced by taurocholic acid in the C. difficile strains CD196, M68, BI9, and 630, as well as inhibits growth and decreases the cytotoxicity of C. difficile culture supernatants to Vero cells when used at a concentration of 0.0003%.[3] Fecal levels of isolithocholic acid are decreased in a rat model of high-fat diet-induced obesity compared with rats fed a normal diet.[4]
Reference:
[1].Batta, A.K., Salen, G., and Shefer, S.Transformation of bile acids into iso-bile acids by Clostridium perfringes: Possible transport of 3β-hydrogen via the coenzymeHepatology5(6)1126-1131(1985)
[2].Borriello, S.P., and Owen, R.W.The metabolism of lithocholic acid and lithocholic acid-3-α-sulfate by human fecal bacteriaLipids17(7)477-482(1982)
[3].Thanissery, R., Winston, J.A., and Theriot, C.M.Inhibition of spore germination, growth, and toxin activity of clinically relevant C. difficile strains by gut microbiota derived secondary bile acidsAnaerobe4586-100(2017)
[4].Lin, H., An, Y., Tang, H., et al.Alterations of bile acids and gut microbiota in obesity induced by high fat diet in rat modelJ. Agric. Food Chem.67(13)3624-3632(2019)
| Cas No. | 1534-35-6 | SDF | |
| 别名 | 异石胆酸,isoLCA | ||
| 化学名 | (3β,5β)-3-hydroxy-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])C[C@@H](O)CC[C@]4(C)[C@@]3([H])CC[C@@]21C | ||
| 分子式 | C24H40O3 | 分子量 | 376.6 |
| 溶解度 | DMSO : 28.57 mg/mL (75.87 mM; Need ultrasonic) | 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 | 2.6553 mL | 13.2767 mL | 26.5534 mL |
| 5 mM | 0.5311 mL | 2.6553 mL | 5.3107 mL |
| 10 mM | 0.2655 mL | 1.3277 mL | 2.6553 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。
Human gut bacteria produce ΤΗ17-modulating bile acid metabolites
Nature 2022 Mar;603(7903):907-912.PMID:35296854DOI:10.1038/s41586-022-04480-z.
The microbiota modulates gut immune homeostasis. Bacteria influence the development and function of host immune cells, including T helper cells expressing interleukin-17A (TH17 cells). We previously reported that the bile acid metabolite 3-oxolithocholic acid (3-oxoLCA) inhibits TH17 cell differentiation1. Although it was suggested that gut-residing bacteria produce 3-oxoLCA, the identity of such bacteria was unknown, and it was unclear whether 3-oxoLCA and other immunomodulatory bile acids are associated with inflammatory pathologies in humans. Here we identify human gut bacteria and corresponding enzymes that convert the secondary bile acid lithocholic acid into 3-oxoLCA as well as the abundant gut metabolite Isolithocholic Acid (isoLCA). Similar to 3-oxoLCA, isoLCA suppressed TH17 cell differentiation by inhibiting retinoic acid receptor-related orphan nuclear receptor-γt, a key TH17-cell-promoting transcription factor. The levels of both 3-oxoLCA and isoLCA and the 3α-hydroxysteroid dehydrogenase genes that are required for their biosynthesis were significantly reduced in patients with inflammatory bowel disease. Moreover, the levels of these bile acids were inversely correlated with the expression of TH17-cell-associated genes. Overall, our data suggest that bacterially produced bile acids inhibit TH17 cell function, an activity that may be relevant to the pathophysiology of inflammatory disorders such as inflammatory bowel disease.
Polyclonal murine and rabbit antibodies for the bile acid Isolithocholic Acid
J Immunoassay Immunochem 2015;36(3):233-52.PMID:24845039DOI:10.1080/15321819.2014.924419.
Bile acids are relevant markers for clinical research. This study reports the production of antibodies for Isolithocholic Acid, the isomer of the extensively studied lithocholic acid. The IgG titer and affinity maturation were monitored during the immunizations of three mice and two rabbits. In both animal models, polyclonal antibodies with a high selectivity and affinity were produced. The development of a direct competitive ELISA with a test midpoint of 0.69 ± 0.05 μ g/L and a measurement range from 0.09-15 μg/L is reported. Additionally, the crystal structure of Isolithocholic Acid is described for the first time.
Reduction of 3-keto-5 beta-cholanoic acid to lithocholic and isolithocholic acids by human liver cytosol in vitro
Biochim Biophys Acta 1985 Oct 23;837(1):20-6.PMID:2932163doi
The formation of lithocholic and isolithocholic acids from 3-keto-5 beta-cholanoic acid by human liver cytosol was examined in vitro. Liver cytosol was incubated at various pH levels with 3-keto-5 beta-cholanoic acid in a phosphate buffer containing NADPH or NADH; the products formed were analyzed by gas chromatography. Results showed that human liver cytosol reduced 3-keto-5 beta-cholanoic acid to lithocholic acid at a pH level of 7.0 or above and to Isolithocholic Acid at a pH level of 6.0 or below when NADPH was used as a coenzyme, and it was reduced to Isolithocholic Acid only when NADH was used. Furthermore, two peaks for the reducing enzymes could be clearly found by column chromatography of Affi-Gel Blue. These results indicate that human liver cytosol contains two enzymes acting on reduction of 3-keto-5 beta-cholanoic acid to lithocholic and isolithocholic acids, which are dependent on the pH level and the use of NADPH or NADH in vitro. Since the 3 beta-dehydrogenation was inhibited by the addition of pyrazole, an alcohol dehydrogenase inhibitor or ethanol, and the major peak of 3 beta-hydroxysteroid dehydrogenase coincided with the peak of alcohol dehydrogenase on Affi-Gel Blue chromatography, at least some of the cytosolic 3 beta-hydroxysteroid dehydrogenase seemed to be identical to or to have characteristics similar to alcohol dehydrogenase.
Enzyme-linked immunosorbent assay (ELISA) for the anthropogenic marker Isolithocholic Acid in water
J Environ Manage 2016 Nov 1;182:612-619.PMID:27544648DOI:10.1016/j.jenvman.2016.08.023.
Bile acids are promising chemical markers to assess the pollution of water samples with fecal material. This study describes the optimization and validation of a direct competitive enzyme-linked immunosorbent assay for the bile acid Isolithocholic Acid (ILA). The quantification range of the optimized assay was between 0.09 and 15 μg/L. The assay was applied to environmental water samples. Most studies until now were focused on bile acid fractions in the particulate phase of water samples. In order to avoid tedious sample preparation, we undertook to evaluate the dynamics and significance of ILA levels in the aqueous phase. Very low concentrations in tap and surface water samples made a pre-concentration step necessary for this matrix as well as for wastewater treatment plant (WWTP) effluent. Mean recoveries for spiked water samples were between 97% and 109% for tap water and WWTP influent samples and between 102% and 136% for WWTP effluent samples. 90th percentiles of intra-plate and inter-plate coefficients of variation were below 10% for influents and below 20% for effluents and surface water. ILA concentrations were quantified in the range of 33-72 μg/L in influent, 21-49 ng/L in effluent and 18-48 ng/L in surface water samples. During wastewater treatment the ILA levels were reduced by more than 99%. ILA concentrations of influents determined by ELISA and LC-MS/MS were in good agreement. However, findings in LC-ELISA experiments suggest that the true ILA levels in concentrated samples are lower due to interfering effects of matrix compounds and/or cross-reactants. Yet, the ELISA will be a valuable tool for the performance check and comparison of WWTPs and the localization of fecal matter input into surface waters.
Biotransformation of lithocholic acid by rat hepatic microsomes: metabolite analysis by liquid chromatography/mass spectrometry
Drug Metab Dispos 2008 Feb;36(2):442-51.PMID:18039809DOI:10.1124/dmd.107.017533.
Lithocholic acid is a lipid-soluble hepatotoxic bile acid that accumulates in the liver during cholestasis. A potential detoxification pathway for lithocholic acid involves hydroxylation by hepatic cytochrome P450 (P450) enzymes. The purpose of the present study was to identify the hepatic microsomal metabolites of lithocholic acid by liquid chromatography/mass spectrometry and to determine the P450 enzymes involved. Incubation of lithocholic acid with rat hepatic microsomes and NADPH produced murideoxycholic acid (MDCA), Isolithocholic Acid (ILCA), and 3-keto-5beta-cholanic acid (3KCA) as major metabolites and 6-ketolithocholic acid and ursodeoxycholic acid as minor metabolites. Experiments with hepatic microsomes prepared from rats pretreated with P450 inducers and with inhibitory antibodies indicated that CYP2C and CYP3A enzymes contribute to microsomal MDCA formation. Results obtained with a panel of recombinant P450 enzymes and CYP2D6 antiserum showed that CYP2D1 can also catalyze MDCA formation. Similar experimental evidence revealed that formation of 3KCA was mediated primarily by CYP3A enzymes. ILCA formation appeared to be catalyzed by a distinct pathway mediated largely by microsomal non-P450 enzymes. Based on the results obtained using lithocholic acid and 3KCA as substrates, a mechanism for the formation of ILCA involving a geminal diol intermediate is outlined. In conclusion, lithocholic acid was extensively metabolized by multiple P450 enzymes with the predominant biotransformation pathway being hydroxylation at the 6beta-position. This study provides an insight into possible routes of detoxification of lithocholic acid.