Bile acid
Introduction
Bile acids are a group of steroid acids found predominantly in the bile of mammals. They play a crucial role in the digestion and absorption of lipids in the small intestine. Bile acids are synthesized from cholesterol in the liver and are conjugated with amino acids glycine or taurine before being secreted into the bile. They are essential for the emulsification of dietary fats and the absorption of fat-soluble vitamins.
Synthesis and Metabolism
Primary Bile Acids
Primary bile acids are synthesized in the liver from cholesterol through a series of enzymatic reactions. The two main primary bile acids in humans are cholic acid and chenodeoxycholic acid. The synthesis of these bile acids involves the action of several enzymes, including cholesterol 7α-hydroxylase (CYP7A1), which is the rate-limiting enzyme in the pathway.
Conjugation
Before being secreted into the bile, primary bile acids are conjugated with either glycine or taurine. This conjugation increases their solubility and reduces their toxicity. Conjugated bile acids are often referred to as bile salts. The conjugation process involves the enzyme bile acid-CoA:amino acid N-acyltransferase (BAAT).
Enterohepatic Circulation
Bile acids are secreted into the bile and stored in the gallbladder. During digestion, they are released into the small intestine, where they aid in the emulsification and absorption of dietary fats. Approximately 95% of bile acids are reabsorbed in the ileum and returned to the liver via the portal vein in a process known as enterohepatic circulation. The remaining 5% are excreted in the feces.
Function
Emulsification of Fats
Bile acids play a critical role in the digestion of dietary fats. They act as detergents, breaking down large fat globules into smaller micelles, which increases the surface area for the action of pancreatic lipase. This process is essential for the efficient digestion and absorption of triglycerides and other lipids.
Absorption of Fat-Soluble Vitamins
Bile acids are also important for the absorption of fat-soluble vitamins, including vitamins A, D, E, and K. These vitamins are incorporated into micelles formed by bile acids, which facilitates their transport across the intestinal mucosa.
Types of Bile Acids
Primary Bile Acids
Primary bile acids are synthesized in the liver and include cholic acid and chenodeoxycholic acid. These bile acids are conjugated with glycine or taurine before being secreted into the bile.
Secondary Bile Acids
Secondary bile acids are formed in the intestine by the action of bacterial enzymes on primary bile acids. The main secondary bile acids in humans are deoxycholic acid and lithocholic acid. These secondary bile acids can be reabsorbed and returned to the liver, where they may be reconjugated and secreted into the bile.
Clinical Significance
Bile Acid Malabsorption
Bile acid malabsorption (BAM) is a condition characterized by the excessive loss of bile acids in the stool, leading to chronic diarrhea and malabsorption of fats. BAM can be caused by diseases affecting the ileum, such as Crohn's disease, or by surgical resection of the ileum. Treatment often involves the use of bile acid sequestrants, which bind bile acids in the intestine and reduce their loss.
Cholestasis
Cholestasis is a condition characterized by impaired bile flow, which can lead to the accumulation of bile acids in the liver and bloodstream. This can result in jaundice, itching, and liver damage. Causes of cholestasis include liver diseases such as primary biliary cholangitis and primary sclerosing cholangitis, as well as bile duct obstructions.
Bile Acid Sequestrants
Bile acid sequestrants are a class of drugs used to treat hypercholesterolemia and certain types of diarrhea. These drugs bind bile acids in the intestine, preventing their reabsorption and promoting their excretion in the feces. This leads to an increased conversion of cholesterol to bile acids in the liver, thereby lowering blood cholesterol levels.
Research and Future Directions
Recent research has focused on the role of bile acids as signaling molecules. Bile acids activate nuclear receptors such as the farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor 1 (GPBAR1), also known as TGR5. These receptors regulate various metabolic processes, including glucose and lipid metabolism, and have potential therapeutic implications for metabolic diseases such as diabetes and non-alcoholic fatty liver disease (NAFLD).