Murideoxycholic Acid
(Synonyms: 鼠脱氧胆酸) 目录号 : GC40966A secondary bile acid
Cas No.:668-49-5
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
Murideoxycholic acid (MDCA) is a secondary bile acid produced from α-muricholic acid and β-muricholic acid.[1] It is also a metabolite of lithocholic acid in liver S9 fractions from humans and other species.[2] MDCA prevents gallstone formation in hamsters fed a lithogenic diet but does not resolve gallstones in prairie dogs fed a high cholesterol diet.[3],[4] Gallstones formed during MDCA administration after a high cholesterol diet are comprised of an insoluble calcium salt of murideoxycholyl taurine.[4] In humans, MDCA is rapidly absorbed and is metabolized as an endogenous bile acid with a half-life of approximately 3.5 days.[5]
Reference:
[1]. Wahlström, A., Sayin, S.I., Marschall, H.-I., et al. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 24(1), 41-50 (2016).
[2]. Thakare, R., Alamoudi, J.A., Gautam, N., et al. Species differences in bile acids II. Bile acid metabolism. J. Appl. Toxicol. 38(10), 1336-1352 (2018).
[3]. Cohen, B.I., Matoba, N., Mosbach, E.H., et al. Bile acids substituted in the 6 position prevent cholesterol gallstone formation in the hamster. Gastroenterology 98(2), 397-405 (1990).
[4]. Cohen, B.I., Ayyad, N., Mosbach, E.H., et al. Replacement of cholesterol gallstones by murideoxycholyl taurine gallstones in prairie dogs fed murideoxycholic acid. Hepatology 14(1), 158-168 (1991).
[5]. Khallou, J., Legrand-Defretin, V., Parquet, M., et al. Metabolism and time-course excretion of murideoxycholic acid, a 6 β-hydroxylated bile acid, in humans. J. Hepatol. 17(3), 364-372 (1993).
| Cas No. | 668-49-5 | SDF | |
| 别名 | 鼠脱氧胆酸 | ||
| 化学名 | 5β-3α,6β-dihydroxy-cholan-24-oic acid | ||
| Canonical SMILES | C[C@H](CCC(O)=O)[C@@]1([H])CC[C@@]2([H])[C@]3([H])C[C@@H](O)[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@@]21C | ||
| 分子式 | C24H40O4 | 分子量 | 392.6 |
| 溶解度 | 20mg/mL in ethanol or DMSO, 30mg/mL in DMF | 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 | 2.5471 mL | 12.7356 mL | 25.4712 mL |
| 5 mM | 0.5094 mL | 2.5471 mL | 5.0942 mL |
| 10 mM | 0.2547 mL | 1.2736 mL | 2.5471 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。
Replacement of cholesterol gallstones by murideoxycholyl taurine gallstones in prairie dogs fed Murideoxycholic Acid
Hepatology 1991 Jul;14(1):158-68.PMID:2066064DOI:10.1002/hep.1840140126.
The effect of two hydrophilic bile acids, Murideoxycholic Acid (3 alpha,6 beta-dihydroxy-5 beta-cholanoic acid) and ursodeoxycholic acid, on cholesterol and bile acid metabolism and hepatic pathology and gallstone composition was studied in the prairie dog. Cholesterol gallstones were induced by feeding a diet containing 1.2% cholesterol for 75 days. The animals were divided into six groups, and gallstone regression was studied as follows: groups 2 and 5, chow plus 0.2% cholesterol; groups 3 and 6, chow plus 0.2% cholesterol plus 0.15% ursodeoxycholic acid; groups 4 and 7, chow plus 0.2% cholesterol plus 0.15% Murideoxycholic Acid. Animals in groups 2 to 4 were killed after an additional 6 wk; animals in groups 5 to 7 were killed after an additional 12 wk. Gallstone dissolution did not occur in any group. The gallstones in groups 2, 3, 5 and 6 were typical cholesterol aggregates, as determined by polarized light microscopy and Fourier transform infrared spectrometry. The gallstones of the Murideoxycholic Acid group were large, solitary, dark stones that appeared radiopaque under 22 kVp x-ray examination. Scanning electron microscopy showed that in these stones the cholesterol crystals had been replaced by an amorphous material, both within the stone and on the stone surface. Chemical analysis indicated that at the end of 12 wk the calcium/sodium salt of the taurine conjugate of Murideoxycholic Acid (murideoxycholyl taurine) comprised 70% of the stones; protein, cholesterol and small amounts of other bile salts were also present. In vitro studies confirmed the insolubility of the sodium and calcium salts of murideoxycholyl taurine. These studies indicate that the hydrophilic bile acids, Murideoxycholic Acid and ursodeoxycholic acid, did not achieve gallstone dissolution under the conditions used. In the animals fed Murideoxycholic Acid, an insoluble calcium salt of murideoxycholyl taurine replaced cholesterol as the major constituent of gallbladder stones. This is the first example of an insoluble dihydroxy taurine-conjugated bile acid; administration of the unconjugated bile acid induced precipitation of a kind of gallstone not previously reported. The final result was transformation of cholesterol stones to bile salt stones.
Metabolism and time-course excretion of Murideoxycholic Acid, a 6 beta-hydroxylated bile acid, in humans
J Hepatol 1993 Mar;17(3):364-72.PMID:8315264DOI:10.1016/s0168-8278(05)80219-3.
The metabolism and time-courses of urinary and fecal excretions of Murideoxycholic Acid (MDCA; 3 alpha,6 beta-dihydroxy-5 beta-cholanoic acid), a 6 beta-hydroxylated bile acid, was investigated in man. The study was carried out in two groups of subjects. Six cholecystectomized patients fitted with a cystic duct drain ingested 100 mg of a tracer dose of 3H-MDCA. Time-course of radioactivity in plasma was then followed for an 8-h period. Biliary, urinary and fecal excretions of radioactivity were measured for a 5-day period and excreted MDCA metabolites were identified. Five lithiasic patients with intact enterohepatic circulation ingested 500 mg of the same tracer dose of 3H-MDCA. Radioactivity in plasma was followed for a 49-h period and urinary and fecal excretions of radioactivity were measured daily for 7 days. In the first group, the excretion of the radioactivity by the three routes (bile+urine+feces) reached 97.8 +/- 1.5% of the ingested dose but dropped to 75 +/- 8.3% (urine+feces) in patients in the second group. In cholecystectomized patients, the estimation of intestinal MDCA absorption was dependent on cystic duct drain flow rate and gave values ranging from 20% to 87%. The biological half-life of MDCA in lithiasic patients averaged 3.4 +/- 0.7 days. Radioactivity appeared in the plasma in the first hour and reached a maximum 6 and 3 h after the beginning of the experiment in group I and II respectively. In the second group, another peak of radioactivity in plasma was observed just after breakfast.(ABSTRACT TRUNCATED AT 250 WORDS)
Highly selective bile acid hydroxylation by the multifunctional bacterial P450 monooxygenase CYP107D1 (OleP)
Biotechnol Lett 2020 May;42(5):819-824.PMID:31974648DOI:10.1007/s10529-020-02813-4.
Objective: Regio- and stereoselective hydroxylation of lithocholic acid (LCA) using CYP107D1 (OleP), a cytochrome P450 monooxygenase from the oleandomycin synthesis pathway of Streptomyces antibioticus. Results: Co-expression of CYP107D1 from S. antibioticus and the reductase/ferredoxin system PdR/PdX from Pseudomonas putida was performed in Escherichia coli whole cells. In vivo hydroxylation of LCA exclusively yielded the 6β-OH product Murideoxycholic Acid (MDCA). In resting cells, 19.5% of LCA was converted to MDCA within 24 h, resulting in a space time yield of 0.04 mmol L-1 h-1. NMR spectroscopy confirmed the identity of MDCA as the sole product. Conclusions: The multifunctional P450 monooxygenase CYP107D1 (OleP) can hydroxylate LCA, forming MDCA as the only product.
Bile acids substituted in the 6 position prevent cholesterol gallstone formation in the hamster
Gastroenterology 1990 Feb;98(2):397-405.PMID:2295395DOI:10.1016/0016-5085(90)90831-k.
The aim of the present study is to examine the efficacy of 6-hydroxy substituted bile acids on the prevention of cholesterol gallstones in a new hamster model of cholesterol cholelithiasis. Male golden Syrian hamsters were fed a nutritionally adequate semipurified lithogenic diet consisting of casein, cornstarch, soluble starch, butterfat, corn oil, and cellulose plus 0.3% cholesterol. Six different bile acids were added to this diet at the 0.05% level: chenodeoxycholic acid, ursodeoxycholic acid, hyodeoxycholic acid, Murideoxycholic Acid, 6 beta-methyl-hyodeoxycholic acid, and 6 alpha-methyl-murideoxycholic acid. At the end of the 6-wk feeding period, the control group receiving the lithogenic diet had a 55% incidence of gallstones. It was found that all bile acids had inhibited the formation of cholesterol gallstones; complete prevention of gallstones was observed with all 4 3,6-dihydroxy bile acids, whereas chenodeoxycholic acid and ursodeoxycholic acid were somewhat less effective (80% and 75% prevention, respectively). The accumulation of cholesterol in serum and liver induced by the lithogenic diet was inhibited to some extent by all of the bile acids; hyodeoxycholic acid, Murideoxycholic Acid, and 6 beta-methyl hyodeoxycholic acid were most effective in this respect. The administered bile acids tended to predominate in bile in the case of chenodeoxycholic acid, hyodeoxycholic acid, and 6 beta-methyl-hyodeoxycholic acid. In contrast, ursodeoxycholic acid seemed to be converted to chenodeoxycholic acid and Murideoxycholic Acid to hyodeoxycholic acid. Only 4% of the 6-methyl analogue of Murideoxycholic Acid, 6 alpha-methyl-murideoxycholic acid, was recovered in gallbladder bile. These experiments show that the new hamster model of cholesterol cholelithiasis is suitable for gallstone-prevention studies. It was not possible to draw definite conclusions concerning the mechanism of action of the administered bile acids on the basis of cholesterol saturation or the presence of liquid crystals. The detailed mechanism of gallstone prevention by hydrophilic bile acids in this model remains to be elucidated.
Species Differences of Bile Acid Redox Metabolism: Tertiary Oxidation of Deoxycholate is Conserved in Preclinical Animals
Drug Metab Dispos 2020 Jun;48(6):499-507.PMID:32193215DOI:10.1124/dmd.120.090464.
It was recently disclosed that CYP3A is responsible for the tertiary stereoselective oxidations of deoxycholic acid (DCA), which becomes a continuum mechanism of the host-gut microbial cometabolism of bile acids (BAs) in humans. This work aims to investigate the species differences of BA redox metabolism and clarify whether the tertiary metabolism of DCA is a conserved pathway in preclinical animals. With quantitative determination of the total unconjugated BAs in urine and fecal samples of humans, dogs, rats, and mice, it was confirmed that the tertiary oxidized metabolites of DCA were found in all tested animals, whereas DCA and its oxidized metabolites disappeared in germ-free mice. The in vitro metabolism data of DCA and the other unconjugated BAs in liver microsomes of humans, monkeys, dogs, rats, and mice showed consistencies with the BA-profiling data, confirming that the tertiary oxidation of DCA is a conserved pathway. In liver microsomes of all tested animals, however, the oxidation activities toward DCA were far below the murine-specific 6β-oxidation activities toward chenodeoxycholic acid (CDCA), ursodeoxycholic acid, and lithocholic acid (LCA), and 7-oxidation activities toward Murideoxycholic Acid and hyodeoxycholic acid came from the 6-hydroxylation of LCA. These findings provided further explanations for why murine animals have significantly enhanced downstream metabolism of CDCA compared with humans. In conclusion, the species differences of BA redox metabolism disclosed in this work will be useful for the interspecies extrapolation of BA biology and toxicology in translational researches. SIGNIFICANCE STATEMENT: It is important to understand the species differences of bile acid metabolism when deciphering biological and hepatotoxicology findings from preclinical studies. However, the species differences of tertiary bile acids are poorly understood compared with primary and secondary bile acids. This work confirms that the tertiary oxidation of deoxycholic acid is conserved among preclinical animals and provides deeper understanding of how and why the downstream metabolism of chenodeoxycholic acid dominates that of cholic acid in murine animals compared with humans.