Bile acids


NADPH.Formation of bile acids    The primary bile acids are synthesized in the liver from cholesterol. The 7-hydroxylation of cholesterol is the first and principal regulatory step in the biosynthesis of bile acids and is catalyzed by cholesterol 7-hydroxylase. These are cholic acid (found in the largest amount) and chenodeoxycholic acid. Subsequent hydroxylation steps are also catalyzed by monooxygenases. and cytochrome P450. a microsomal enzyme. . A typical monooxygenase. it requires oxygen.

the ratio of the glycine to the taurine conjugates is normally 3:1.    The pathway of bile acid biosynthesis divides early into one subpathway leading to cholyl-CoA." . and another pathway leading to chenodeoxycholylCoA . Conjugation takes place in peroxisomes. In humans. A second pathway in mitochondria involving the 27hydroxylation of cholesterol by sterol 27hydroxylase as the first step is responsible for a significant proportion of the primary bile acids synthesized. the bile acids and their conjugates are assumed to be in a salt form²hence the term "bile salts. characterized by an extra -OH group on position 12. In the alkaline bile. The primary bile acids enter the bile as glycine or taurine conjugates.

including cholesterol. the primary and secondary bile acids are absorbed almost exclusively in the ileum.Most Bile Acids Return to the Liver in the Enterohepatic Circulation   Although products of fat digestion. and 98±99% are returned to the liver via the portal circulation. This is known as the enterohepatic circulation. However. is not reabsorbed to any significant extent. are absorbed in the first 100 cm of small intestine. lithocholic acid. because of its insolubility. .

   Only a small fraction of the bile salts escapes absorption and is therefore eliminated in the feces. Each day the small pool of bile acids (about 3±5 g) is cycled through the intestine six to ten times and an amount of bile acid equivalent to that lost in the feces is synthesized from cholesterol. This is accomplished by a system of feedback controls. . Nonetheless. so that a pool of bile acids of constant size is maintained. this represents a major pathway for the elimination of cholesterol.

When the size of the bile acid pool in the enterohepatic circulation increases. FXR is activated and transcription of the cholesterol 7-hydroxylase gene is suppressed. glucagon.Bile Acid Synthesis Is Regulated at the 7-Hydroxylase Step     The principal rate-limiting step in the biosynthesis of bile acids is at the cholesterol 7-hydroxylase reaction. Cholesterol 7-hydroxylase activity is also enhanced by cholesterol of endogenous and dietary origin and regulated by insulin. and thyroid hormone. glucocorticoids. Chenodeoxycholic acid is particularly important in activating FXR. The activity of the enzyme is feedback-regulated via the nuclear bile acid-binding receptor farnesoid X receptor (FXR). .

Enterohepatic circulation of bile salts .

    Of the total bile salts reaching intestine only a very small fraction about 300-500mg/day is excreted through feces The rest is reabsorbed from ileum. reaches liver and re-excreted through bile While bile acids binding resin is given.the reabsorption of bile acid id inhibited Hence more cholesterol gets converted to bile acids and cholesterol is decreased .

Daily volume of secretion is about 500ml Secreted bile is stored in the gall bladder and released on demand The pH of the hepatic duct is 7.and in gall bladder is 7.8.4. An enzyme present in bile is alkaline phosphatase .Bile     Chief secretion of liver.

Functions of bile      Bile acts to some extent as a surfactant. such as the vitamins D. Since bile increases the absorption of fats. bile serves also as the route of excretion for bilirubin. . Without bile salts. K and A. E. Besides its digestive function. undigested. Bilirubin derives from haemoglobin by glucuronidation. it is an important part of the absorption of the fat-soluble substances. The alkaline bile also has the function of neutralizing any excess stomach acid before it enters the ileum. destroying many of the microbes that may be present in the food. helping to emulsify the fats in the food. Bile salts also act as bactericides. a byproduct of red blood cells recycled by the liver. most of the lipids in the food would be passed out in feces. the final section of the small intestine.

Sign up to vote on this title
UsefulNot useful