Bile Acids - The Role Of Bile Acids For Digestion - Definitions

Here is some information on bile production and the role of bile in digestion - the first part is some definitions about liver parts:

SECTION #1
BILIARY STENOSIS
narrowing or constriction of a bile duct

BILIARY TREE
all passageways inside and outside the liver that carry bile to the intestines

BILE
a fluid produced by the liver, stored in the gallbladder, and released into the small intestine to help absorb dietary fats

BILE DUCTS
the tubes through which bile flows

BILE LEAK
a hole in the bile-duct system that causes bile to spill into the abdominal cavity

BILIRUBIN
an orange-colored substance in bile produced by the breakdown of red blood cells

SECTION #2
Bile acid
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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.

Synthesis of bile acids is a major consumer of cholesterol. The body synthesizes 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 (by active transport in the ileum) and recycled. This is referred to as the enterohepatic circulation.

Since bile acids are made from endogenous cholesterol, the enterohepatic circulation of bile acids may be disrupted as a way to lower cholesterol. This is the mechanism of action behind bile acid sequestrants. Bile acid sequestrants bind bile acids in the gut, preventing their reabsorption. The sequestered bile acids are then excreted in the feces.

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
As surfactants or detergents, bile acids are potentially toxic to cells and their levels are tightly regulated. They function directly as signaling molecules in the liver and the intestines by activating a nuclear hormone receptor known as FXR and also NR1H4. This results in inhibition of bile acid synthesis in the liver when bile acid levels are too high. Emerging evidence associates FXR activation with alterations in triglyceride metabolism, glucose metabolism and liver growth.


SECTION #3
FROM ABOUT.COM :

Secretion of Bile and the Role of Bile Acids In Digestion
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Bile is a complex fluid containing water, electrolytes and a battery of organic molecules including bile acids, cholesterol, phospholipids and bilirubin that flows through the biliary tract into the small intestine. There are two fundamentally important functions of bile in all species:


Bile contains bile acids, which are critical for digestion and absorption of fats and fat-soluble vitamins in the small intestine.


Many waste products are eliminated from the body by secretion into bile and elimination in feces.
Adult humans produce 400 to 800 ml of bile daily, and other animals proportionately similar amounts. The secretion of bile can be considered to occur in two stages:


Initially, hepatocytes secrete bile into canaliculi, from which it flows into bile ducts. This hepatic bile contains large quantities of bile acids, cholesterol and other organic molecules.


As bile flows through the bile ducts it is modified by addition of a watery, bicarbonate-rich secretion from ductal epithelial cells.
In species with a gall bladder (man and most domestic animals except horses and rats), further modification of bile occurs in that organ. The gall bladder stores and concentrates bile during the fasting state. Typically, bile is concentrated five-fold in the gall bladder by absorption of water and small electrolytes - virtually all of the organic molecules are retained.

Secretion into bile is a major route for eliminating cholesterol. Free cholesterol is virtually insoluble in aqueous solutions, but in bile, it is made soluble by bile acids and lipids like lethicin. Gallstones, most of which are composed predominantly of cholesterol, result from processes that allow cholesterol to precipitate from solution in bile.

Role of Bile Acids in Fat Digestion and Absorption

Bile acids are derivatives of cholesterol synthesized in the hepatocyte. Cholesterol, ingested as part of the diet or derived from hepatic synthesis is converted into the bile acids cholic and chenodeoxycholic acids, which are then conjugated to an amino acid (glycine or taurine) to yield the conjugated form that is actively secreted into cannaliculi.




Bile acids are amphipathic, that is, they contain both hydrophobic (lipid soluble) and polar (hydrophilic) regions. The cholesterol portion of a bile acid is hydrophobic and the amino acid conjugate is polar and hydrophilic.

Their amphipathic nature enables bile acids to carry out two important functions:

Emulsification of lipid aggregates: Bile acids have detergent action on particles of dietary fat which causes fat globules to break down or be emulsified into minute, microscopic droplets. Emulsification is not digestion per se, but is of importance because it greatly increases the surface area of fat, making it available for digestion by lipases, which cannot access the inside of lipid droplets.


Solubilization and transport of lipids in an aqueous environment: Bile acids are lipid carriers and are able to solubilize many lipids by forming micelles - aggregates of lipids such as fatty acids, cholesterol and monoglycerides - that remain suspended in water. Bile acids are also critical for transport and absorption of the fat-soluble vitamins.
Role of Bile Acids in Cholesterol Homeostasis

Hepatic synthesis of bile acids accounts for the majority of cholesterol breakdown in the body. In humans, roughly 500 mg of cholesterol are converted to bile acids and eliminated in bile every day. This route for elimination of excess cholesterol is probably important in all animals, but particularly in situations of massive cholesterol ingestion.

Interestingly, it has recently been demonstrated that bile acids participate in cholesterol metabolism by functioning as hormones that alter the transcription of the rate-limiting enzyme in cholesterol biosynthesis.

Enterohepatic Recirculation

Large amounts of bile acids are secreted into the intestine every day, but only relatively small quantities are lost from the body. This is because approximately 95% of the bile acids delivered to the duodenum are absorbed back into blood within the ileum.

Venous blood from the ileum goes straight into the portal vein, and hence through the sinusoids of the liver. Hepatocytes extract bile acids very efficiently from sinusoidal blood, and little escapes the healthy liver into systemic circulation. Bile acids are then transported across the hepatocytes to be resecreted into canaliculi. The net effect of this enterohepatic recirculation is that each bile salt molecule is reused about 20 times, often two or three times during a single digestive phase.

It should be noted that liver disease can dramatically alter this pattern of recirculation - for instance, sick hepatocytes have decreased ability to extract bile acids from portal blood and damage to the canalicular system can result in escape of bile acids into the systemic circulation. Assay of systemic levels of bile acids is used clinically as a sensitive indicator of hepatic disease.

Pattern and Control of Bile Secretion

The flow of bile is lowest during fasting, and a majority of that is diverted into the gallbladder for concentration. When chyme from an ingested meal enters the small intestine, acid and partially digested fats and proteins stimulate secretion of cholecystokinin and secretin. As discussed previously, these enteric hormones have important effects on pancreatic exocrine secretion. They are both also important for secretion and flow of bile:

Cholecystokinin: The name of this hormone describes its effect on the biliary system - cholecysto = gallbladder and kinin = movement. The most potent stimulus for release of cholecystokinin is the presence of fat in the duodenum. Once released, it stimulates contractions of the gallbladder and common bile duct, resulting in delivery of bile into the gut.


Secretin: This hormone is secreted in response to acid in the duodenum. Its effect on the biliary system is very similar to what was seen in the pancreas - it simulates biliary duct cells to secrete bicarbonate and water, which expands the volume of bile and increases its flow out into the intestine.
The processes of gallbladder filling and emptying described here can be visualized using an imaging technique called scintography. This procedure is utilized as a diagnostic aid in certain types of hepatobiliary disease.



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