Conjugated Bile Salts are the product of Bile acids linked with amino acids like glycine and taurine. These bile salts are produced in the body's liver and are chemically synthesized for various studies.
These amphipathic molecules prove to be a significant entity for formulating drugs as they increase their water solubility, improving bioavailability. Therefore, conjugated bile salts must be highly pure and well-tested before using them for drug formulations. In this blog, we shed light on conjugated bile acids and their types, Bile Salt formation, functions, and applications. Lastly, we guide you to find the fine and speciality chemicals suitable for your applications.
What are Conjugated Bile Salts?
Conjugated Bile salts are bile salts chemically bonded to amino acids, such as glycine or taurine. This Bile Acid Conjugation enhances water solubility, surfactant properties, and digestion efficiency.
Chemically, bile acid conjugates are amphipathic steroid molecules synthesized from cholesterol. Being amphipathic in nature, they exhibit cell-signalling functions via nuclear and membrane receptors like FXR and TGR5. Bile acid metabolism occurs in the liver, leading to the Bile liquid formation, which plays a vital role in the breakdown of fat molecules. Before the secretion of these bile acids into bile, they undergo Bile Salt Formation by conjugating with glycine or taurine to form Glycocholic acid (cholic acid+glycine) or Taurocholic acid (cholic acid+taurine), respectively.
Types of Bile Acids
Synthesized in Liver- Primary Bile Acids: Cholic Acid and Chenodeoxycholic acid are synthesized in hepatocytes and then conjugated with glycine or taurine to form Conjugated Bile Salts.
Produced by Gut Microbes- Secondary Bile Acids: Acids like deoxycholic acid (formed from cholic acid) and lithocholic acid (formed from chenodeoxycholic acid) are produced due to the Bile Acid Metabolism of primary bile acids by gut bacteria.
How is Bile Salt Synthesized in the liver?
Bile Salt Synthesis occurs in hepatocytes via a multistep process:
Cholesterol is first catabolised into primary bile acids like cholic acid and chenodeoxycholic acid.
Next, these bile acids undergo a conjugation step with either glycine or taurine to form conjugated bile salts with increased water solubility.
Further, these conjugated bile salts are stored in the gall bladder and released into the small intestine when required.
The Bile Salt Absorption process occurs in the ileum, where up to 95% of the conjugated bile salts are reabsorbed and returned to the liver for reuse.
What are the differences between Conjugated Bile Salts vs. Unconjugated Bile Salts?
Here are the key differences between conjugated bile salts and unconjugated bile salts:
Types of Conjugated Bile Salts
Primary Bile Salts: They are derived from primary bile acids
a.Sodium Glycocholate: Cholic Acid + Glycine
b. Sodium Taurocholate: Cholic Acid + Taurine
c. Sodium Glycochenodeoxycholate: Chenodeoxycholic acid + Glycine
d. Sodium Taurochenodeoxycholate: Chenodeoxycholic Acid + Taurine
Secondary Bile Salts: They are formed as a result of the metabolism of primary bile acids in the intestine
a. Sodium Glycodeoxycholate: Deoxycholic Acid + Glycine
b. Sodium Taurodeoxycholate: Deoxycholic Acid + Taurine
c. Sodium Glycolithocholate: Lithocholic acid + Glycine
d. Sodium Taurolithocholate: Lithocholic Acid + Taurine
Functions of Conjugated Bile Salts in Digestion
The conjugated bile salts are responsible for the Bile Salt function, which is to break down large fat globules into smaller droplets, increasing their surface area for the enzyme pancreatic lipase to act on. These bile salts also allow lipid absorption by forming micelles which transport monoglycerides, cholesterol, and fat-soluble vitamins (A, D, E, K) to the intestinal lining.
Also, bile salts assist in eliminating excess cholesterol from the body by converting it into bile acids for excretion and are responsible for maintaining intestinal microbiome balance.
In the absence of conjugated bile salts, fat digestion would be inefficient, leading to malabsorption disorders and steatorrhea (fatty stools). They prevent the risks of gallstone formation by maintaining cholesterol in soluble form. A deficiency in bile salt can also cause liver dysfunction disorders.
Pharmaceutical Applications of Conjugated Bile Salts
Improving Drug Solubility and Bioavailability: The conjugated bile salts enhance the lipophilic drug’s solubility in water and gastrointestinal permeability by forming micelles. Chenodeoxycholic acid is used in drug formulations to enhance the bioavailability of cyclosporine, an immunosuppressant important during organ transplantation. Bile salts can also improve the solubility of poorly water-soluble drugs like Fenofibrate, enhancing its absorption in the gut.
Used to treat Hepatic Disorders: UDCA (Ursodeoxycholic acid), a secondary bile acid, when conjugated with Glycine or Taurine, is used to treat cholestatic liver diseases, including primary biliary cholangitis. It modulates bile acid composition, reduces hepatocellular toxicity, and ameliorates cholestasis.
Targeted Drug Delivery Systems: Bile salt-based micellar and nanoparticle formulations are being studied to deliver target-specific drugs. For example, taurocholate-modified nanocarriers have shown better cellular uptake of doxorubicin, thus improving the drug’s therapeutic efficacy while reducing off-target toxicity. Alkan-Onyuksel et al. studied the development of a mixed micellar formulation by solubilizing paclitaxel (an anticancer drug) in a bile salt-phospholipid mixture. The results showed an amplified solubilization of the drug with an increase in the molar ratio of bile salt/phospholipid and the total lipid concentration.
Antimicrobial Properties: Bile salt function includes antimicrobial activity due to its surfactant-like nature. Sodium taurocholate exhibits bactericidal activity against S. aureus.
Oral-Route Drug Delivery: Sodium glycocholate is used as an absorption enhancer in oral drug formulations as it improves the intestinal permeability of peptide-based therapeutics like insulin. These salts offer a potential alternative to the subcutaneous route of drug administration to manage diabetes.
Nucleic Acid Delivery: The detergent-like properties of bile salts are being leveraged to deliver nucleic acids. The siRNA delivery system formulated using bile salts has shown promising results for treating cancers by enhancing gene silencing efficiency.
Savan Patel and his team studied a strategy to achieve extrahepatic delivery of mRNA using bile acids (cholic acid, chenodeoxycholic acid, deoxycholic acid) for Lipid Nanoparticle (LNP) synthesis. As per the results, the Bile Acid-LNPs exhibited promising results for gastrointestinal or immune cell delivery of mRNA.
Where to buy pure Bile Salts?
Conjugated bile salts used in pharma \and biotech industries must be highly pure (>98%), and HPLC must be tested to confirm the chemical identity and purity of the bile salt. It must be free from Endotoxin (< 0.1 EU/mg) when used for cell culture and drug development studies.
When used for drug solubilization studies, Sodium Taurocholate must be >98% pure. Sodium Glycocholate must have more than >99% purity when used for liposome stabilization.
Highly pure Bile Salt Conjugates appear white to off-white crystalline or powder form. It must completely dissolve in both water and organic solvents. The pure solution of Bile Salts has a pH range of 7 to 8.5. Pure Bile Salts have heavy metals of less than 10 ppm and should not have any microbial contamination. These Salts have a two or more years of shelf life if stored in the right conditions (-20°C to 4°C, protected from light and moisture).
At Advent, we offer high-purity Conjugated Bile Salts with a Certificate of Analysis. We are an ISO 9001:2015 & ISO 14001:2015 Certified Company, supporting R&D since the time of inception. To explore more fine and speciality chemicals, visit our website now.
