7-Ketolithocholic acid
(Synonyms: 3Α-羟基-7-氧代-5Β-胆烷酸,3α-Hydroxy-7-oxo-5β-cholanic acid) 目录号 : GC39474
7-Ketolithocholic acid (3α-hydroxy-7-oxygen-5β-cholic acid)是一种胆汁酸，7-Ketolithocholic acid可被吸收，7-ketolithocholic acid抑制内源性胆汁酸的产生，并可影响分泌胆汁胆固醇。
Cas No.:4651-67-6
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
| Clinical experiment [1]: | |
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Animal models |
5 male subjects with gallstones (mean age, 55 yr) |
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Preparation Method |
400 mg/day of uniformly labeled 7-ketolithocholic acid (sp act, 1000 * 100 dpm/mg) was fed to each patient daily for 2 wk and the specific activities of chenodeoxycholic acid and ursodeoxycholic acid in bile were measured every other day. |
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Dosage form |
400 mg/day for 2 wk£¨ Intravenous injection£© |
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Applications |
7-ketolithocholic acid is absorbed, and suppresses endogenous bile acid production and biliary cholesterol secretion. |
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References: [1]. Salen G, Verga D, et,al. Effect of 7-ketolithocholic acid on bile acid metabolism in humans. Gastroenterology. 1982 Aug;83(2):341-7. PMID: 7084613. |
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7-Ketolithocholic acid (3α-hydroxy-7-oxygen-5β-cholic acid) is a kind of bile acid, 7-Ketolithocholic acid can be absorbed, 7-ketolithocholic acid inhibits the production of endogenous bile acid, and can affect the secretion of biliary cholesterol[1，2].
After 7-ketolithocholic acid (400 mg/day) was administered orally for 14 days, biliary bile acid composition changed: The proportion of cholic acid decreased (from 45% to 19%), deoxycholic acid decreased (from 15% to 10%), chenodeoxycholic acid increased markedly (from 36% to 59%), ursodeoxycholic acid increased (from 36% to 59%), ursodeoxycholic acid increased (from 2% to 7%), and lithocholic acid increased (from 2% to 5%), while only trace amounts of 7-ketolithocholic acid were detected. During this treatment, the biliary lithogenic index fell from 2.6 to 0.9 and was accompanied by a pronounced drop in biliary cholesterol concentration[2].
References:
[1]. Choucair I, Nemet I, et,al. Quantification of bile acids: a mass spectrometry platform for studying gut microbe connection to metabolic diseases. J Lipid Res. 2020 Feb;61(2):159-177. doi: 10.1194/jlr.RA119000311. Epub 2019 Dec 9. PMID: 31818878; PMCID: PMC6997600.
[2]. Salen G, Verga D, et,al. Effect of 7-ketolithocholic acid on bile acid metabolism in humans. Gastroenterology. 1982 Aug;83(2):341-7. PMID: 7084613.
7-Ketolithocholic acid (3α-hydroxy-7-oxygen-5β-cholic acid)是一种胆汁酸，7-Ketolithocholic acid可被人体吸收，7-ketolithocholic acid抑制内源性胆汁酸的产生，可影响胆汁胆固醇的分泌[1，2]。
口服 7-酮石胆酸（400 毫克/天）14 天后，胆汁酸成分发生变化:胆酸比例下降（从 45% 下降到 19%），脱氧胆酸下降（从 15% 下降到10%），鹅去氧胆酸显着增加（从 36% 到 59%），熊去氧胆酸增加（从 36% 到 59%），熊去氧胆酸增加（从 2% 到 7%），石胆酸增加（从 2% 到5%), 而仅检测到痕量的 7-酮石胆酸。在此治疗期间，胆道结石指数从 2.6 降至 0.9，并伴随着胆道胆固醇浓度的显着下降[2]。
| Cas No. | 4651-67-6 | SDF | |
| 别名 | 3Α-羟基-7-氧代-5Β-胆烷酸,3α-Hydroxy-7-oxo-5β-cholanic acid | ||
| Canonical SMILES | C[C@H](CCC(O)=O)[C@H]1CC[C@@]2([H])[C@]3([H])C(C[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)=O | ||
| 分子式 | C24H38O4 | 分子量 | 390.56 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,Ethanol: 30 mg/ml,Ethanol:PBS (pH 7.2) (1:3): 0.25 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 | 2.5604 mL | 12.8021 mL | 25.6043 mL |
| 5 mM | 0.5121 mL | 2.5604 mL | 5.1209 mL |
| 10 mM | 0.256 mL | 1.2802 mL | 2.5604 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。
Effect of 7-Ketolithocholic acid on bile acid metabolism in humans
Gastroenterology 1982 Aug;83(2):341-7.PMID:7084613doi
The effect of 7-Ketolithocholic acid on biliary bile acid composition, cholesterol saturation, and as an intermediate in the conversion of chenodeoxycholic acid to ursodeoxycholic acid was investigated in 5 subjects with gallstones. After 7-Ketolithocholic acid (400 mg/day) was administered orally for 14 days, biliary bile acid composition changed: The proportion of cholic acid decreased (from 45% to 19%), deoxycholic acid decreased (from 15% to 10%), chenodeoxycholic acid increased markedly (from 36% to 59%), ursodeoxycholic acid increased (from 36% to 59%), ursodeoxycholic acid increased (from 2% to 7%), and lithocholic acid increased (from 2% to 5%), while only trace amounts of 7-Ketolithocholic acid were detected. During this treatment, the biliary lithogenic index fell from 2.6 to 0.9 and was accompanied by a pronounced drop in biliary cholesterol concentration. After biliary bile acid levels became constant [24-14C]chenodeoxycholic acid was given intravenously as a pulse-label, and the resultant biliary ursodeoxycholic acid and lithocholic acid specific activity curves showed a precursor--product relationship with chenodeoxycholic acid. Similarly, when uniformly labeled 7-[24-14C]ketolithocholic acid was fed (400 mg/day, 1000 +/- 100 dpm/mg) the specific activities of biliary chenodeoxycholic acid and ursodeoxycholic acid became constant and approximated each other, but these were only 75% as high as the fed 7-Ketolithocholic acid. These results indicate that 7-Ketolithocholic acid is absorbed, and suppresses endogenous bile acid production and biliary cholesterol secretion. Both isotopic experiments infer that ursodeoxycholic acid and lithocholic acid are formed from chenodeoxycholic acid and not from 7-Ketolithocholic acid. The reduction in biliary lithogenic index and in cholesterol concentration suggest that low doses of 7-Ketolithocholic acid may be effective in dissolving gallstones.
Ursodeoxycholic acid, 7-Ketolithocholic acid, and chenodeoxycholic acid are primary bile acids of the nutria (Myocastor coypus)
Gastroenterology 1986 Mar;90(3):702-9.PMID:3943698DOI:10.1016/0016-5085(86)91126-1.
Because ursodeoxycholic and chenodeoxycholic acids are interconverted in humans via 7-Ketolithocholic acid, bile acid metabolism was studied in the nutria (Myocastor coypus), the bile of which is known to contain these three bile acids. Relative concentrations of ursodeoxycholic (37% +/- 20%), 7-ketolithocholic (33% +/- 17%), and chenodeoxycholic (17% +/- 9%) acids in gallbladder bile were unchanged by 5-20 h of complete biliary diversion (n = 7). Injection of either [14C]cholesterol, [14C]ursodeoxycholic, [14C]7-Ketolithocholic acid, or a mixture of [7 beta-3H]chenodeoxycholic acid and [14C]chenodeoxycholic acid into bile fistula nutria demonstrated that all three bile acids can be synthesized hepatically from cholesterol, that they are interconverted sparingly (2%-5%) by the liver, but that 7-Ketolithocholic acid is an intermediate in the hepatic transformation of chenodeoxycholic acid to ursodeoxycholic acid. An animal that had been fed antibiotics showed an unusually elevated concentration of ursodeoxycholic acid in gallbladder and hepatic bile, suggesting that bacterial transformation of ursodeoxycholic acid in the intestine may be a source of some biliary chenodeoxycholic acid and 7-Ketolithocholic acid.
Reduction of 7-Ketolithocholic acid by human liver enzyme preparations in vitro
Am J Physiol 1989 Jan;256(1 Pt 1):G67-71.PMID:2912152DOI:10.1152/ajpgi.1989.256.1.G67.
The formation of chenodeoxycholic and ursodeoxycholic acids from 7-Ketolithocholic acid by human liver preparations was examined in vitro. Liver preparations were incubated with 7-Ketolithocholic acid at pH 5.5 in a sodium-potassium-phosphate buffer containing NADPH or NADH. The products formed were analyzed by gas chromatography and gas chromatography-mass spectrometry. Results showed that chenodeoxycholic and ursodeoxycholic acids could be formed from 7-Ketolithocholic acid by human liver enzyme(s). The enzyme(s) required NADPH but not NADH as coenzyme and was localized largely in the microsomes. The conjugated 7-Ketolithocholic acid, especially the taurine conjugated, was predominantly reduced to chenodeoxycholic acid, whereas the unconjugated 7-Ketolithocholic acid was not reduced well to either chenodeoxycholic acid or ursodeoxycholic acid. Thus the reduction of 7-Ketolithocholic acid by human liver enzyme(s) was found to be dependent on whether the substrate was conjugated or not.
Ursodeoxycholic acid, chenodeoxycholic acid, and 7-Ketolithocholic acid are primary bile acids of the guinea pig
J Lipid Res 1990 Jul;31(7):1301-6.PMID:2401860doi
Guinea pig gallbladder bile contains chenodeoxycholic acid (62 +/- 5%), ursodeoxycholic acid (8 +/- 5%), and 7-Ketolithocholic acid (30 +/- 5%). All three bile acids became labeled to the same specific activity within 30 min after [3H]cholesterol was injected into bile fistula guinea pigs. When a mixture of [3H]ursodeoxycholic acid and [14C]chenodeoxycholic acid was infused into another bile fistula guinea pig, little 3H could be detected in either chenodeoxycholic acid or 7-Ketolithocholic acid. But, 14C was efficiently incorporated into ursodeoxycholic and 7-ketolithocholic acids. Monohydroxylated bile acids make up 51% and ursodeoxycholic acid 38% of fecal bile acids. After 3 weeks of antibiotic therapy, lithocholic acid was reduced to 6% of the total, but ursodeoxycholic acid (5-11%) and 7-ketolithocholic (15-21%) acid persisted in bile. Lathosterol constituted 19% of skin sterols and was detected in the feces of an antibiotic-fed animal. After one bile fistula guinea pig suffered a partial biliary obstruction, ursodeoxycholic and 7-ketolithocholic acids increased to 46% and 22% of total bile acids, respectively. These results demonstrate that chenodeoxycholic acid, ursodeoxycholic acid, and 7-Ketolithocholic acid can all be made in the liver of the guinea pig.
Metabolism in man of 7-Ketolithocholic acid: precursor of cheno- and ursodeoxycholic acids
Am J Physiol 1980 Sep;239(3):G161-6.PMID:7435569DOI:10.1152/ajpgi.1980.239.3.G161.
To define the metabolism of 7-Ketolithocholic acid in man, studies were carried out in gallstone patients with normal liver function. 7-[24-14C]ketolithocholic acid or its glycine or taurine conjugates were injected intravenously, and the chemical form of radioactivity appearing in bile was determined to define hepatic biotransformation. To study intestinal absorption 7-[24-14C]ketolithocholic acid was infused into the jejunum and ileum, respectively, and the chemical form of radioactivity appearing in peripheral blood and bile was assessed. 7-Ketolithocholic acid was extensively reduced in the liver to chenic acid and, to lesser extent, to ursodeoxycholic acid. Hepatic reduction was similar for both unconjugated as well as glycine- and taurine-conjugated 7-Ketolithocholic acid. 7-Ketolithocholic acid was well absorbed. There was no biotransformation in the small intestinal lumen or during absorption, because all radioactivity recovered from the lumen or in peripheral blood was in unchanged 7-Ketolithocholic acid. Biotransformation products in bile after jejunal infusion were similar to those after intravenous injection. The studies indicate that 7-Ketolithocholic acid is likely to be a physiological precursor of ursodeoxycholic acid in healthy man.