Glycolithocholic Acid
(Synonyms: 甘氨石胆酸,Lithocholylglycine) 目录号 : GC43778
A glycine-conjugated form of lithocholic acid
Cas No.:474-74-8
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
Glycolithocholic acid is a glycine-conjugated form of the secondary bile acid lithocholic acid.[1] It is increased in livers of mice that are fed diets supplemented with ursodeoxycholic acid.[2] Glycolithocholic acid levels are decreased in lean mice treated with obestatin.[3] Serum glycolithocholic acid levels increase with age in children.[4]
甘氨酸结合的次级胆汁酸黄石胆酸（Glycolithocholic acid）是黄石胆酸的一种结合形式。[1] 它在添加了优胆酸的饮食中的小鼠肝脏中升高。[2] 瘦小鼠接受obestatin治疗后，血清甘氨酸结合的黄石胆酸水平降低。[3] 儿童血清中的甘氨酸结合的黄石胆酸水平随着年龄增长而升高。[4]
Reference:
[1]. Lefebvre, P., Cariou, B., Lien, F., et al. Role of bile acids and bile acid receptors in metabolic regulation. Physiol. Rev. 89(1), 147-191 (2009).
[2]. Eyssen, H.J., Parmentier, G.G., and Mertens, J.A. Sulfate bile acids in germ-free and conventional mice. Eur. J. Biochem. 66(3), 507-514 (1976).
[3]. Cowan, E., Kimar, P., Burch, K.J., et al. Treatment of lean and diet-induced obesity (DIO) mice with a novel stable obestatin analogue alters plasma metabolite levels as detected by untargeted LC-MS metabolomics. Metabolomics 12(124), (2016).
[4]. Semba, R.D., Gonzalez-Freier, M., Moaddel, R., et al. Environmental enteric dysfunction is associated with altered bile acid metabolism. J. Pediatr. Gastenterol. Nutr. 64(4), 536-540 (2017).
n.
| Cas No. | 474-74-8 | SDF | |
| 别名 | 甘氨石胆酸,Lithocholylglycine | ||
| 化学名 | N-[(3α,5β)-3-hydroxy-24-oxocholan-24-yl]-glycine | ||
| Canonical SMILES | C[C@H](CCC(NCC(O)=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 | C26H43NO4 | 分子量 | 433.6 |
| 溶解度 | 20mg/mL in ethanol & 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 | 2.3063 mL | 11.5314 mL | 23.0627 mL |
| 5 mM | 0.4613 mL | 2.3063 mL | 4.6125 mL |
| 10 mM | 0.2306 mL | 1.1531 mL | 2.3063 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。
Synthesis of sulfate esters of lithocholic acid, Glycolithocholic Acid, and taurolithocholic acid with sulfur trioxide-triethylamine
J Lipid Res 1977 Jul;18(4):491-5.PMID:894140doi
The facile synthesis of lithocholic acids sulfates by a procedure that produced the desired products in over 90% yield is described. Lithocholic acid sulfate and Glycolithocholic Acid sulfate were synthesized by reacting lithocholic acid or Glycolithocholic Acid with sulfur trioxide-triethylamine complex in dimethylformamide for 0.5-1 hr. Taurolithocholic acid sulfate was obtained by conjugating lithocholic acid sulfate with taurine in dimethylformamide at 90 degrees C for 0.5 hr. The one-pot synthesis of taurolithocholic acid sulfate starting from lithocholic acid is also described. This procedure, which generated lithocholic acid sulfate in situ, produced taurolithocholic acid sulfate in 98% yield, compared to an overall yield of less than 10% obtained by previously published procedures.
Biliary lipid secretion in the rat. The uncoupling of biliary cholesterol and phospholipid secretion from bile acid secretion by sulfated Glycolithocholic Acid
Biochim Biophys Acta 1987 Nov 21;922(2):136-44.PMID:3676338DOI:10.1016/0005-2760(87)90147-0.
Glycolithocholic Acid and its sulfated derivative are major metabolites of the secondary bile acid lithocholic acid in man. Both compounds are known to induce cholestasis in experimental animals. We compared the effects of these endogenous hepatotoxins on bile production and biliary lipid composition in rats with chronic biliary drainage. The compounds were administered enterally at relatively low rates (5-50% of the rats' endogenous bile acid secretion in these experiments) to simulate enterohepatic circulation. Both compounds were substantially secreted into bile (more than 90% of dose); sulfated Glycolithocholic Acid unchanged and Glycolithocholic Acid after hepatic hydroxylation predominantly in the form of glyco-beta-muricholic acid (cf. Kuipers et al. (1986) Am. J. Physiol. 251, G189-G194). Neither Glycolithocholic Acid nor its sulfated derivative affected the biliary excretion of endogenous bile acids or bile flow in these experiments. In spite of this, phospholipid and cholesterol secretion were significantly reduced by sulfated Glycolithocholic Acid but were not altered by Glycolithocholic Acid. Phospholipid and cholesterol secretion rapidly decreased to 25 and 50% of their initial values, respectively, at biliary output rates of sulfated Glycolithocholic Acid up to 2 mumol/h, and did not further decrease when this output was increased to 6 mumol/h. Small unilamellar liposomes consisting of cholesterol, [Me-14C]choline-labeled phosphatidylcholine, phosphatidylserine and [3H]cholesteryl oleate in a 5:4:1:0.1 molar ratio were employed to label intrahepatic lipid pools. Administration of sulfated Glycolithocholic Acid slightly reduced bile acid synthesis from [3H]cholesteryl oleate, but significantly reduced the biliary secretion of [14C]phospholipid. Glycolithocholic Acid did not affect the hepatic processing of liposomal lipids. It is concluded that sulfated Glycolithocholic Acid at low doses causes the uncoupling of biliary lipid secretion from that of bile acids, which might represent in initiating event in sulfated Glycolithocholic Acid hepatotoxicity.
Inhibition of Human Sulfotransferase 2A1-Catalyzed Sulfonation of Lithocholic Acid, Glycolithocholic Acid, and Taurolithocholic Acid by Selective Estrogen Receptor Modulators and Various Analogs and Metabolites
J Pharmacol Exp Ther 2019 Jun;369(3):389-405.PMID:30918069DOI:10.1124/jpet.119.256255.
Lithocholic acid (LCA) is a bile acid associated with adverse effects, including cholestasis, and it exists in vivo mainly as conjugates known as glyco-LCA (GLCA) and tauro-LCA (TLCA). Tamoxifen has been linked to the development of cholestasis, and it inhibits sulfotransferase 2A1 (SULT2A1)-catalyzed dehydroepiandrosterone (DHEA) sulfonation. The present study was done to characterize the sulfonation of LCA, GLCA, and TLCA and to investigate whether triphenylethylene (clomifene, tamoxifen, toremifene, ospemifene, droloxifene), benzothiophene (raloxifene, arzoxifene), tetrahydronaphthalene (lasofoxifene, nafoxidine), indole (bazedoxifene), and benzopyran (acolbifene) classes of selective estrogen receptor modulator (SERM) inhibit LCA, GLCA, and TLCA sulfonation. Human recombinant SULT2A1, but not SULT2B1b or SULT1E1, catalyzed LCA, GLCA, and TLCA sulfonation, whereas each of these enzymes catalyzed DHEA sulfonation. LCA, GLCA, and TLCA sulfonation is catalyzed by human liver cytosol, and SULT2A1 followed the substrate inhibition model with comparable apparent K m values (≤1 µM). Each of the SERMs inhibited LCA, GLCA, and TLCA sulfonation with varying potency and mode of enzyme inhibition. The potency and extent of inhibition of LCA sulfonation were attenuated or increased by structural modifications to toremifene, bazedoxifene, and lasofoxifene. The inhibitory effect of raloxifene, bazedoxifene, and acolbifene on LCA sulfonation was also observed in HepG2 human hepatocellular carcinoma cells. Overall, among the SERMs investigated, bazedoxifene and raloxifene were the most effective inhibitors of LCA, GLCA, and TLCA sulfonation. These findings provide insight into the structural features of specific SERMs that contribute to their inhibition of SULT2A1-catalyzed LCA sulfonation. Inhibition of LCA, GLCA, and TLCA detoxification by a SERM may provide a biochemical basis for adverse effects associated with a SERM.
Cholestasis induced by sulphated Glycolithocholic Acid in the rat: protection by endogenous bile acids
Clin Sci (Lond) 1985 Feb;68(2):127-34.PMID:3967462DOI:10.1042/cs0680127.
Sulphated Glycolithocholic Acid (SGLC) causes cholestasis in experimental animals, despite its sulphated form. In the present study, the cholestatic potency and the pharmacokinetics of SGLC were investigated in rats under two conditions: (a) in the presence of an intact circulating bile acid pool and (b) after exhaustion of the bile acid pool by 24 h of bile diversion. Intravenous administration of SGLC (8 mumol/100 g body weight) to rats with an intact bile acid pool did not cause cholestasis. However, biliary phospholipid and cholesterol concentrations were reduced by 40% and 29% respectively during the first hour after administration. When the same dose of the bile acid was injected in rats with a 24 h biliary drainage, a complete cessation of bile production was observed within 1 h. Twelve hours after the onset of cholestasis, bile production gradually increased again, showed a marked overshoot, and reached control levels after 3 days. In the recovery phase, biliary phospholipid and cholesterol concentrations were greatly reduced. The absence of endogenous bile acids did not change the hepatic clearance rate of a tracer dose of radiolabelled SGLC, but markedly decreased its biliary excretion rate. It was concluded that the hepatotoxic effect of SGLC is much more pronounced in rats with an exhausted bile acid pool, possibly due to a slower biliary excretion of the toxic compound. This phenomenon may have clinical implications for patients with a contracted bile acid pool.
Bile secretion of sulfated Glycolithocholic Acid is required for its cholestatic action in rats
Am J Physiol 1992 Feb;262(2 Pt 1):G267-73.PMID:1539660DOI:10.1152/ajpgi.1992.262.2.G267.
To test our hypothesis that the cholestatic action of sulfated Glycolithocholic Acid (SGLC) in the rat is related to its interaction with calcium in the biliary tree [R. van der Meer, R. J. Vonk, and F. Kuipers. Am. J. Physiol. 254 (Gastrointest. Liver Physiol. 17): G644-G649, 1988], we have now compared its effects on bile formation in control Wistar rats and mutant Groningen Yellow (GY) Wistar rats. Intravenous injection of 0.6 mumol/100 g body wt of [14C]SGLC in unanesthetized rats with permanent biliary drainage did not induce cholestasis in either of the strains; however, its biliary secretion was strongly impaired in GY rats (12% dose at 1 h after injection vs. 95% dose in controls). Injection of 6.0 and 12.0 mumol/100 g body wt of [14C]SGLC caused an almost complete cessation of bile flow in control rats within 3 and 1 h, respectively. In contrast, administration of the same doses did not cause cholestasis in GY rats. Cholestasis in control rats was preceded by coprecipitation of [14C]SGLC and calcium in bile and incomplete biliary recovery of radioactivity. The hepatic content 15 min after injection of [14C]SGLC (6.0 mumol/100 g body wt) was similar in control and GY rats, 51 and 49% of the dose, respectively. Administration of Glycolithocholic Acid, the unsulfated parent compound of SGLC (6.0 mumol/100 g body wt), induced a rapid but reversible cessation of bile flow in both controls and GY rats; in this case no precipitation was observed in bile. This study shows that rapid bile secretion of SGLC is required for the induction of cholestasis.(ABSTRACT TRUNCATED AT 250 WORDS)