Endogenous Metabolite

The primary components of bile are bile acids. They are processed steroids that the liver tissue produces from bile [1].

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.[2]

[1]. Quantification of bile acids: a mass spectrometry platform for studying gut microbe connectionto metabolic diseases. J Lipid Res. 2020 Feb;61(2):159-177.

[2]. Effect of 7-ketolithocholic acid on bile acid metabolism in humans. Gastroenterology. 1982 Aug;83(2):341-7.

7-Oxolithocholic acid is a bile acid formed by introducing an additional oxo substituent at the 7-position of lithocholic acid. It is a human metabolite. It is a bile acid, monohydroxy-5β-cholanic acid, oxo-5β-cholanic acid, and 3α-hydroxysteroid. Functionally, it is related to lithocholic acid. It is the conjugate acid of 7-oxolithocholate. Bile acids (BAs) have a variety of biological functions, including the absorption of lipids and fat-soluble vitamins, and acting as signaling molecules by directly activating specific cellular receptors. Bile acids are synthesized by host and microbial pathways, and they are increasingly recognized for their involvement in regulating many pathways associated with metabolic diseases, including lipid and glucose metabolism, energy expenditure, and inflammation. Due to the unique and diverse physicochemical properties of bile acids (BAs), their quantitative analysis can present numerous challenges. Therefore, developing a quantitative analytical method that combines good accuracy, precision, extraction efficiency, and minimizes matrix effects for structurally diverse human and mouse bile acids is extremely challenging. This article describes the development and clinical validation of a stable isotope dilution liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the quantitative analysis of multiple primary and secondary bile acids in human and mouse biomatrices. We also used this method to investigate the role of gut microbiota in the generation of structurally specific bile acids in humans and mice. We examined the circulating levels of specific bile acids and compared them in an age- and sex-matched clinical case-control study of patients with type 2 diabetes mellitus (T2DM) and non-diabetic patients. Circulating bile acids associated with type 2 diabetes mellitus (T2DM) include multiple 12α-hydroxy bile acids (taurocholic acid, taurodeoxycholic acid, glycodeoxycholic acid, deoxycholic acid, and 3-ketodeoxycholic acid), while taurodeoxycholic acid is negatively correlated with diabetes. The liquid chromatography-tandem mass spectrometry (LC/MS/MS) platform described in this article can serve as a powerful high-throughput research tool for investigating the potential roles of structurally specific bile acids and gut microbiota in physiological and disease processes. [1]

C₂₄H₃₈O₄

390.56

390.277

4651-67-6

444262

Typically exists as White to off-white solid at room temperature

1.1±0.1 g/cm3

545.9±25.0 °C at 760 mmHg

205ºC

298.0±19.7 °C

0.0±3.3 mmHg at 25°C

1.535

4.25

2

4

4

28

645

9

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

DXOCDBGWDZAYRQ-AURDAFMXSA-N

InChI=1S/C24H38O4/c1-14(4-7-21(27)28)17-5-6-18-22-19(9-11-24(17,18)3)23(2)10-8-16(25)12-15(23)13-20(22)26/h14-19,22,25H,4-13H2,1-3H3,(H,27,28)/t14-,15+,16-,17-,18+,19+,22+,23+,24-/m1/s1

(4R)-4-[(3R,5S,8R,9S,10S,13R,14S,17R)-3-hydroxy-10,13-dimethyl-7-oxo-1,2,3,4,5,6,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pentanoic acid

7-Ketolithocholic acid; 7 Ketolithocholic acid; 4651-67-6; 7-Ketolithocholic acid; Nutriacholic acid; 3alpha-Hydroxy-7-oxo-5beta-cholanic acid; 7-Oxolithocholic acid; 3.alpha.-Hydroxy-7-oxo-5.beta.-cholanic acid; 3a-Hydroxy-7-oxo-5b-cholanic acid; 3alpha-Hydroxy-7-oxo-5beta-cholan-24-oic Acid; Nutriacholic Acid; 3α-Hydroxy-7-oxo-5β-cholanic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~256.04 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.40 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (6.40 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)