Gallbladder bile acids

Cowles, R.L., Lee, J.-Y., Gallaher, D.D., Stuefer-Powell, C.L., and Carr, T.P. 2002. Dietary stearic acid alters gallbladder bile acid composition in hamsters fed cereal-based diets. J. Nutr. 132, 3119-3122. 

Bile is produced by hepatocytes from several essential components, including water, bile acids, cholesterol, phospholipids and bilirubin. Most of these substances are absorbed in the distal ileum and delivered to the hepatocyte via the portal vein. The liver excretes approximately 500-600 mL of bile each day, most of which is stored in the gallbladder. Bile acids have an important function in emulsifying lipids in the digestive tract, which improves digestion by pancreatic lipases. 

A group of several similar compounds present in bile, a digestive fluid secreted by the liver, and stored in the gallbladder. Bile acids are (1) produced by the breakdown of cholesterol in the liver, and (2) converted into bile salts by the alkaline constituents of the bile. 

Gallstones. Bile acids keep cholesterol soluble in gallbladder bile. Therefore, they are used for the dissolution of cholesterol gallstones. Initial treatment... 

Cliolestyramine (Questran) and colestipol (Colestid) are examples of bile acid sequestrants. Bile, which is manufactured and secreted by the liver and stored in the gallbladder, emulsifies fat and lipids as these products pass through the intestine Once emulsified, fats and lipids are readily absorbed in the intestine These drug bind to bile acids to form an insoluble substance that cannot be absorbed by the intestine, so it is secreted in the feces. With increased loss of bile acids, the liver uses cholesterol to manufacture more bile This is followed by a decrease in cholesterol levels. 

Bicarbonate is only one of the digestive chemicals that get secreted into the small intestines. Bile acids play a role as well. Bile is made in the liver, stored in the gallbladder, and, when needed, secreted into the small intestines via the bile duct. Bile plays an essential role in the breakdown of fat by dissolving it in the small intestine, much like soap dissolves oil on a frying pan. This breaks the fat down into small droplets. These fat droplets are broken down even further by other intestinal enzymes so that they can be absorbed by the body. 

It is impossible to determine the relative contributions of each of these pathways to total bile-acid biosynthesis, due to the nature of the data. Some values were obtained from patients whose gallbladders had been surgically removed other patients would be atypical due to illness, and many data were obtained from experimental animals, which may metabolise these compounds differently from humans. Also, the exact order of many of the reactions is not known, since the intermediates may act as substrates for more than one enzyme. Further details for these reactions can be found in reviews by Chiang, Moore et al. and Fuchs et al ... 

Gallbladder contraction ejects a bolus of bile acids into the small bowel where they participate in fat digestion. 

Many sites of exposure to bile in the body are associated with the development of cancer, e.g. the oesophagus, gallbladder and bile duct, pancreas, small intestine and colon (reviewed in ref. 2). One explanation for increased cancer at these sites could be that bile acids stimulate carcinogenesis via DNA-damaging effects. This chapter provides an overview of research conducted in relation to establishing the genotoxic and carcinogenic effects of bile acids. 

Results obtained in this way were helpful, but of limited value. The analyses told us whether or not the bile was supersaturated with cholesterol, but did not tell us whether the abnormality was due to too much cholesterol, too few bile acids, too few phospholipids or to some combined defect. The next step, therefore, was to measure the hour-by-hour bile lipid-secretion rates using marker-corrected perfusion techniques. These assume that, in response to the perfusion stimulus (such as an intra-duodenal amino acid mixture), the gallbladder remains tonically contracted throughout and steady-state conditions ensue. 

Samples of gallbladder bile obtained in this way were analysed for bile acids, phospholipids and cholesterol (from which the cholesterol saturation indices were derived). Biliary bile-acid composition was then measured by HPLC. The vesicles were separated from micelles by sucrose density gradient ultra-centrifugation and the cholesterol microcrystal nucleation time measured as described above. 

Bile. The liver forms a thin secretion (bile) that is stored in the gallbladder after water and salts have been extracted from it. From the gallbladder, it is released into the duodenum. The most important constituents of bile are water and inorganic salts, bile acids and bile salts (see p. 314), phospholipids, bile pigments, and cholesterol. Bile salts, together with phospholipids, emulsify insoluble food lipids and activate the lipases. Without bile, fats would be inadequately cleaved, if at all, resulting in fatty stool (steatorrhea). Resorption of fat-soluble vitamins would also be affected. 

Before leaving the liver, a large proportion of the bile acids are activated with CoA and then conjugated with the amino acids g/ycine or taurine (2 cf A). In this way, cholic acid gives rise to glycocholic acid and taurocholic acid. The liver bile secreted by the liver becomes denser in the gallbladder as a result of the removal of water (bladder bile 3). 

The liver secretes about 1 L of bile daily. Bile flow and composition depend on the secretory activity of the hepatic cells that line the biliary canaliculi. As the bile flows through the biliary system of ducts, its composition can be modified in the ductules and ducts by the processes of reabsorption and secretion, especially of electrolytes and water. For example, osmotically active compounds, including bile acids, transported into the bile promote the passive movement of fluid into the duct lumen. In the gallbladder, composition of the bile is modified further through reabsorptive processes. 

These agents have also been found to increase the incidence of symptomatic gallbladder disease, including cholecystitis and cholangitis. This is probably the result of the alterations responsible for jaundice and bile acid changes described above. 

Bile consists of a watery mixture of organic and inorganic compounds. Phosphatidylcholine (lecithin, see p. 201) and bile salts (conjugated bile acids) are quantitatively the most important organic components of bile. Bile can either pass directly from the liver where it is synthesized into the duodenum through the common bile duct, or be stored in Ihe gallbladder when not immediately needed for digestion. 

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