Bile acids

Bile acids are steroid acids found predominantly in the bile of mammals. They are produced in the liver by the oxidation of cholesterol, and are stored in gallbladder and secreted into the intestine in the form of salts. They act as surfactants, emulsifying lipids and assisting with their absorption and digestion.

Cholic Acid vs Other Bile Acids

Synthesis of bile acids is a major consumer of cholesterol. The body synthetizes about 800 mg of cholesterol per day and about half of that is used for bile acid synthesis. In total about 20-30 grams of bile acids are secreted into the intestine daily; about 90% of excreted bile acids are reabsorbed and recycled.

The chemical distinctions between different bile acids are minute, depending only on the presence or absence of hydroxyl groups on positions 3, 7, and 12.

In humans, the most important bile acids are cholic acid and chenodeoxycholic acid, and their conjugates with taurine and glycine (glycocholate and taurocholate). Some mammals synthesize predominantly deoxycholic acid.

The principal bile acids are:

• Cholic acid
• Chenodeoxycholic acid
• Deoxycholic acid
• Taurocholic acid
• Glycocholic acid

Information about Bile acids

Bile acids are a large family of molecules that have a steroidal structure and are synthesized from cholesterol in the liver and actively secreted along with cholesterol and phospholipids into the bile. Bile flowing from the liver is concentrated in the gallbladder and, in response to a meal, released into the upper intestine. In the intestines, bile acids act as detergents and help to emulsify fats, aiding in their digestion and absorption.

Mechanism of action of Bile acids

After participating in digestion in the small bowel, bile acids are almost completely (95%) reabsorbed in the distal ileum and then retaken up from portal blood by the liver (enterohepatic circulation). The primary bile acids synthesized in the liver are cholic and chenodeoxycholic acid which are typically conjugated to glycine or taurine before secretion. In the intestine, the primary bile acids are often converted by colonic bacteria to the secondary bile acids, predominantly deoxycholic acid and lithocholic acid. The reabsorbed bile acids are transported to the liver in portal blood. Conjugated bile acids are then retaken up by hepatocytes via the sodium taurocholate cotransporter (NTCT), while unconjugated bile acids are taken up by organic anion transporters that also take up bilirubin and other anions. The total bile acid pool in humans is tightly controlled by a coordinated regulation of expression of genes involved with synthesis, secretion, reabsorption and reuptake of bile acids by the liver. The major components of the bile acid pool are cholic and chenodeoxycholic acid with lesser amounts deoxycholic and lithocholic acid and minor amounts of ursodeoxycholic acid.

Bile Acids

Bile acids also act as signaling molecules and are important in regulation of their own synthesis, uptake and secretion as well as control of cholesterol synthesis and regulation of lipid and glucose metabolism. Bile acid levels are increased in the serum and liver in patients with obstructive jaundice or cholestasis and, perhaps because of their inherent detergent activities, can cause hepatocyte injury. Thus, increased bile acid levels in hepatocytes may account for some of the liver damage in cholestatic liver diseases.

Bile acids can be used as therapeutic agents, particularly in patients with cholestatic liver diseases where administered bile acids (such as ursodeoxycholic acid) replace the more lipophilic and toxic bile acids that accumulate during cholestasis.

Gallstones and Bile Acids

Bile acids are also useful for the medical treatment (dissolution) of gallstones by increasing bile acid and decreasing cholesterol concentrations in bile (causing a less saturated bile). Bile acids can also be useful as replacement therapy in patients with bile acid synthetic defects. Finally, the other metabolic effects of bile acids can be useful in treating metabolic diseases including nonalcoholic steatohepatitis.

List of Bile acids

Four bile acids are currently approved for use in the United States and several others are under active investigation.

1. Cholic acid is used for treatment of inherited defects in bile acid synthesis, chenodeoxycholic (chenodiol) and
2. Ursodeoxycholic (ursodiol) acid for gallstone dissolution, and obeticholic and ursodiol for chronic cholestatic liver diseases, specifically primary biliary cirrhosis.
3. Obeticholic acid is under evaluation as therapy of other liver diseases including sclerosing cholangitis and nonalcoholic steatohepatitis.
4. Ursodiol is used off label to prevent, treat or ameliorate several uncommon forms of liver disease, including intrahepatic cholestasis of pregnancy, sinusoidal obstruction syndrome, graft-vs-host disease, cystic fibrosis associated liver disease, parenteral nutrition related liver injury and even acute, drug induced liver injury. The long term efficacy in ameliorating the course of these diseases is, however, unproven.

Bile acids Resources
Latest articles Most recent articles Ongoing trials	Wikipedia

• Chenodiol (Chenodeoxycholic Acid)
• Cholic Acid
• Obeticholic Acid
• Ursodiol (Ursodeoxycholic Acid)