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Bile acids are polar, water-soluble acidic steroids formed from cholesterol. In addition to being quantitatively the most important elimination products of cholesterol, bile acids are essential for the absorption of fat and fat soluble vitamins. Regardless of the pathogenesis, all liver diseases have consequences for bile acid turnover, and primary defects in bile acid production and transport have consequences for liver function.


Synthesis of Bile Acids

Conversion of cholesterol into bile acids illustrates the high capacity of the liver to convert lipids into excretable water-soluble products. The reactions and enzyme systems involved in this conversion are similar to those involved in detoxication and elimination of various drugs: hydroxylations, oxidations, side-chain shortening, and conjugations. In contrast to detoxication reactions, however, some of the reactions are highly specific and subject to metabolic control. The end result of the conversion of both cholesterol and various lipophilic drugs is biliary or renal elimination of a water-soluble compound.

The size of the normal bile acid pool in adults is about 2 to 4 g, and this represents the total bile acid content in the liver, intestine, bile ducts, and gallbladder. For comparison, in infants, the pool size related to body surface is approximately half of that of adults. This pool is recycled up to 10 times daily, a process stimulated by the contraction of the gallbladder that occurs after a meal.

The reabsorption of bile acids from the small intestine is very efficient, and the loss of bile acids in feces is normally less than 5%. This loss of bile acids is compensated for by de novo synthesis of bile acids in the liver. Bile acids synthesized in the liver are denoted as primary bile acids, but many of these are chemically modified by the intestinal microflora into secondary bile acids, some of which also are retrieved by the enterohepatic circulation. Bile salts represent approximately 50% of the organic constituents of the bile dry weight, while 25% is made up by phosphatidylcholine. The remaining part consists of cholesterol, bilirubin, and other constituents.

Deficient bile acid synthesis results in reduced production of the primary bile acids, with consequences for the bile flow and possibly also accumulation of abnormal bile acids or bile acid intermediates that may cause cholestasis and liver injury. It should be emphasized that the secretion of bile by the liver is dependent upon the flux of bile acids into the canaliculi.

The major primary bile acids in mammals are cholic acid and chenodeoxycholic acid, the structures of which are shown in Figure 25-1. In human bile most of these two bile acids are present as glycine or taurine conjugates. Conversion of cholesterol into bile acids occurs in the liver, but some of the initial steps in the conversion may also occur in extrahepatic tissues ...

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