Bacteria of the intestinal microbiota (see p. 372) can deconjugate (remove glycine and taurine) bile salts. They can also dehydroxylate carbon 7, producing secondary bile salts such as deoxycholic acid from cholic acid and lithocholic acid from chenodeoxycholic acid.
E. Enterohepatic circulation
Bile salts secreted into the intestine are efficiently reabsorbed (>95%) and reused. The liver actively secretes bile salts via the bile salt export pump. In the intestine, they are reabsorbed in the terminal ileum via the apical sodium (Na+)–bile salt cotransporter and returned to the blood via a separate transport system. [Note: Lithocholic acid is only poorly absorbed.] They are efficiently taken up from blood by the hepatocytes via an isoform of the cotransporter and reused. [Note: Albumin binds bile salts and transports them through the blood as was seen with FA (see p. 181).] The continuous process of secretion of bile salts into the bile, their passage through the duodenum where some are deconjugated then dehydroxylated to secondary bile salts, their uptake in the ileum, and their subsequent return to the liver as a mixture of primary and secondary forms is termed the enterohepatic circulation (Fig. 18.11). Between 15 and 30 g of bile salts are secreted from the liver into the duodenum each day, yet only ~0.5 g (<3%) is lost daily in the feces. Approximately 0.5 g/day is synthesized from cholesterol in the liver to replace the amount lost. Bile acid sequestrants, such as cholestyramine, bind bile salts in the gut and prevent their reabsorption, thereby promoting their excretion. They are used in the treatment of hypercholesterolemia because the removal of bile salts relieves the inhibition on bile acid synthesis in the liver, thereby diverting additional cholesterol into that pathway. [Note: Dietary fiber also binds bile salts and increases their excretion (see p. 365).]
F. Bile salt deficiency: Cholelithiasis
The movement of cholesterol from the liver into the bile must be accompanied by the simultaneous secretion of phospholipid and bile salts. If this dual process is disrupted and more cholesterol is present than can be solubilized by the bile salts and PC present, the cholesterol may precipitate in the gallbladder, leading to cholesterol gallstone disease or cholelithiasis (Fig. 18.12). This disorder is typically caused by a decrease of bile acids in the bile. Cholelithiasis also may result from increased secretion of cholesterol into bile, as seen with the use of fibrates (for example, gemfibrozil) to reduce cholesterol (and TAG) in the blood. Laparoscopic cholecystectomy (surgical removal of the gallbladder through a small incision) is currently the treatment of choice. However, for patients who are unable to undergo surgery, oral administration of chenodeoxycholic acid to supplement the body’s supply of bile acids results in a gradual (months to years) dissolution of the gallstones. [Note: Cholesterol stones account for >85% of cases of cholelithiasis, with bilirubin and mixed stones accounting for the rest].
VI. PLASMA LIPOPROTEINS