Bile Acids

Bile acids (BAs), also known as 24-carbon sterols, are the main components of bile and are a general term for a class of cholic acids synthesized in the liver from cholesterol, which play an important role in fat metabolism and play a protective role for the enterohepatic circulatory system. BAs are amphiphilic steroidal acids, whose production and diversity depend on the metabolism of the host and microorganisms. BOC Sciences provides a broad range of bile acids for use in scientific research, covering biomedical, medical device, food, environmental, and related fields. Every product undergoes rigorous quality control checks to ensure high purity and quality, fulfilling customers' demands for top-quality bile acids. In addition, we offer a range of custom liposome services for you to choose from. At BOC Sciences, you will definitely make a difference in liposomes.

What are Bile Acids?

Bile acids are steroid acids found in the bile of mammals, synthesized in the liver from cholesterol. These molecules are essential for the emulsification and absorption of dietary fats and fat-soluble vitamins in the small intestine. Bile acids are amphipathic molecules with both hydrophobic and hydrophilic regions, allowing them to break down lipid aggregates and enhance the solubility of lipids for absorption in the digestive system. Beyond their digestive role, bile acids function as signaling molecules that regulate gene expression and metabolism. They interact with specific receptors, such as the farnesoid X receptor (FXR), to influence processes like glucose homeostasis, lipid metabolism, and inflammation.

Chemical structure diagrams of some common bile acids. (Zhao, X.; et al, 2022)

Bile Acid Structure

Bile acids have a steroid backbone with one hydrophilic and one hydrophobic face. The hydrophilic side contains hydroxyl groups, while the hydrophobic side has a long hydrophobic chain. This amphipathic nature allows bile acids to interact with both lipids and aqueous solutions, acting as effective emulsifiers. Bile acids are usually conjugated with the amino acids glycine or taurine to enhance their solubility and increase their detergent-like action. Conjugation also influences the interaction of bile acids with bile acid receptors, contributing to their role as signaling molecules in many physiological processes, including glucose metabolism and lipid homeostasis.

Examples of Bile Acids

There are several types of bile acids, with the primary bile acids being cholic acid and chenodeoxycholic acid. These are synthesized in the liver and then conjugated with either glycine or taurine to form bile salts, which are the active components of bile.

• Cholic Acid: A primary bile acid produced in the liver, known for its role in emulsifying fats and aiding their absorption.
• Chenodeoxycholic Acid: Another primary bile acid involved in fat digestion, often used therapeutically to dissolve gallstones.
• Ursodeoxycholic Acid: A secondary bile acid with potential therapeutic benefits, particularly in treating liver diseases and gallstone prevention.
• Deoxycholic Acid: A secondary bile acid formed by bacterial action in the intestines, used in certain medical treatments like fat reduction therapy.
• Deoxycholic acid: A secondary bile acid formed by intestinal bacteria, involved in fat digestion, commonly used in fat reduction treatments.
• Ursocholic acid: A bile acid derivative with hepatoprotective properties, used in treating liver diseases caused by cholestasis.
• Glycoursodeoxycholic acid: A conjugate of ursodeoxycholic acid with glycine, used to improve liver function, especially in primary biliary cholangitis.
• Isodeoxycholic acid: An isomer of deoxycholic acid, involved in bile acid metabolism, potentially useful for liver diseases and cholesterol metabolism.

These bile acids perform diverse functions in the body, from promoting fat absorption to modulating metabolic processes that regulate cholesterol levels.

Bile Acid Resins

Bile acid sequestrants, also known as bile acid resins, are synthetic polymers that bind bile acids in the gastrointestinal tract and prevent their reabsorption into the bloodstream. This binding action promotes the excretion of bile acids and leads to a reduction in cholesterol levels, as the liver must synthesize new bile acids from cholesterol. Bile acid resins like cholestyramine and colesevelam are commonly used in the management of hyperlipidemia, particularly in patients who are unable to tolerate statins or other cholesterol-lowering drugs. These resins not only aid in cholesterol reduction but have also shown promise in the treatment of metabolic disorders such as type 2 diabetes. Studies have indicated that colesevelam, for instance, can reduce glycated hemoglobin (A1C) levels by up to 0.8% without significantly affecting weight. This makes bile acid sequestrants an attractive therapeutic option for conditions associated with dyslipidemia and insulin resistance.

Bile Acid Conjugates

Bile acids are typically conjugated with either glycine or taurine before being secreted into the bile. These conjugated bile acids have enhanced solubility and stability in the aqueous environment of the digestive tract. This conjugation also plays a role in the biological activity of bile acids, as conjugates can interact with bile acid receptors such as FXR, TGR5, and GPBAR1. The binding of bile acids to these receptors influences a variety of biological processes, including glucose metabolism, inflammation, and liver function. Moreover, the regulation of bile acid conjugation affects their interaction with gut microbiota and their role in maintaining intestinal health.

Bile Acid Synthesis

The synthesis of bile acids from cholesterol is a highly regulated process that ensures the body maintains a proper balance between bile acid production and cholesterol levels. The major pathway begins with the conversion of cholesterol into 7α-hydroxycholesterol through the action of cholesterol 7α-hydroxylase. This step is the rate-limiting step of bile acid synthesis, and its activity is regulated by FXR. Once 7α-hydroxycholesterol is formed, it is converted into either cholic acid or chenodeoxycholic acid, depending on the Additionally, bile acid metabolism is influenced by factors like dietary fat intake, liver function, and gut microbiota, which can modify the composition and function of bile acids, impacting metabolic processes such as lipid absorption and glucose homeostasis.

Bile Acid Synthesis Pathway

Bile acid synthesis begins with the conversion of cholesterol into primary bile acids. This process occurs mainly in the liver, and involves multiple enzymatic steps. The two primary bile acids, cholic acid and chenodeoxycholic acid, are synthesized via two distinct pathways: the classic (neutral) pathway and the alternative (acidic) pathway.

• Classic Pathway: This pathway is the dominant route for bile acid synthesis. The rate-limiting step involves the enzyme cholesterol 7α-hydroxylase (CYP7A1), which hydroxylates cholesterol at the 7α position, resulting in the formation of 7α-hydroxycholesterol. This is further metabolized into cholic acid and chenodeoxycholic acid.
• Alternative Pathway: In this pathway, cholesterol is converted to bile acids via a different series of enzymes, leading to the production of chenodeoxycholic acid as the main bile acid.

Once these primary bile acids are produced, they are conjugated with glycine or taurine in the liver to form bile salts. The synthesis of bile acids is tightly regulated by feedback mechanisms involving the FXR receptor and other nuclear receptors.

Bile Acid Function

• Bile acids serve several vital functions in the body, with their primary role being in the digestion and absorption of dietary fats. As amphipathic molecules, bile acids facilitate the breakdown of large fat droplets into smaller micelles, making lipids more accessible to digestive enzymes like pancreatic lipase. This action is essential for the absorption of fat-soluble vitamins (A, D, E, and K) and essential fatty acids.
• In addition to their digestive role, bile acids are also involved in regulating cholesterol metabolism. Through a process known as enterohepatic circulation, bile acids are reabsorbed in the ileum and returned to the liver, where they suppress the synthesis of new cholesterol. This feedback mechanism helps maintain cholesterol homeostasis.
• Bile acids also act as signaling molecules, activating receptors such as FXR and TGR5. FXR regulates various metabolic processes, including lipid and glucose homeostasis, while TGR5 activation leads to the production of factors like glucagon-like peptide-1 (GLP-1), which improves insulin sensitivity and promotes glucose metabolism.

Bile Acid Metabolism

Bile acids undergo extensive metabolism in the liver and intestines, and their circulation is regulated through the enterohepatic system. After bile acids are synthesized in the liver, they are stored in the gallbladder and released into the small intestine during digestion. Once they have completed their role in fat digestion, bile acids are largely reabsorbed in the ileum and transported back to the liver.

In the gut, bile acids undergo microbial transformations, resulting in the production of secondary bile acids like deoxycholic acid and lithocholic acid. These secondary bile acids can have varying effects on metabolic processes, and their composition is influenced by the gut microbiota, highlighting the importance of gut health in bile acid metabolism.

Bile Acid Test

The bile acid test is used to measure the concentration of bile acids in the blood, typically for the diagnosis of liver diseases or disorders related to bile acid metabolism. Elevated bile acid levels in the bloodstream can indicate cholestasis, a condition where bile flow is impaired, often leading to liver damage. Additionally, bile acid testing may be used to monitor the effectiveness of bile acid sequestrants or other medications that influence bile acid levels. These tests help clinicians assess the functioning of the liver and biliary system, providing valuable insights into the patient's metabolic health.

Bile Acid Normal Range

The normal range for bile acids in the blood can vary depending on the laboratory and the specific method used for measurement. However, typical reference ranges for fasting serum bile acid levels are between 1 to 10 µmol/L. Elevated bile acid levels may indicate liver dysfunction, cholestasis, or other metabolic disturbances. Monitoring bile acid concentrations can help guide the treatment of conditions such as non-alcoholic fatty liver disease (NAFLD), primary biliary cholangitis (PBC), and other liver-related disorders.

Bile Acid vs Bile Salt

The terms "bile acid" and "bile salt" are sometimes used interchangeably but refer to slightly different concepts. Bile acids are the free, unbound forms of these molecules, while bile salts refer to the conjugated forms of bile acids. When bile acids are conjugated with glycine or taurine, they become bile salts, which are more soluble and effective in their emulsifying role in digestion.

The key difference lies in their solubility and function: bile acids are more hydrophobic, while bile salts are more hydrophilic due to their conjugation. Both forms of bile acids are essential for the digestion and absorption of fats, but bile salts are the active species in the intestine due to their higher solubility.

Why Choose BOC Sciences' Bile Acids?

• With both mass production and customizable manufacturing capabilities, BOC Sciences can tailor production to meet our clients' needs while ensuring timely delivery.
• BOC Sciences prides itself on providing bile acid products that meet our clients' demands for purity and quality within the field of drug discovery and development.
• Our rigorous quality control measures at BOC Sciences means that our manufacturing process adheres to the highest standards of quality with every product.
• BOC Sciences offers a variety of packaging options and sizes, providing convenience for our clients' storage and handling needs.
• Our broad spectrum of bile acid products, available in various types and sizes, caters to the diverse research purposes and requirements of our clients at BOC Sciences.

Bile acids are far more than just digestive aids; they are potent signaling molecules that regulate various metabolic processes, including lipid metabolism, glucose homeostasis, and inflammation. The growing understanding of bile acid metabolism, particularly through their conjugation and regulation by nuclear receptors like FXR, has opened new avenues for therapeutic applications. BOC Sciences, through its research and development in biologically active compounds and therapeutic agents, contributes to expanding our knowledge of bile acid physiology and its clinical implications. As we continue to explore the roles of bile acids in metabolic diseases, the potential for developing novel therapeutic strategies will only increase.

Reference

1. Zhao, X.; et al. Bile Acid Detection Techniques and Bile Acid-Related Diseases. Front. Physiol. 2022, 13: 826740.