Bile Acid Metabolism
Page 1083 muscle cells in particular take up large amounts of dietary lipids for storage or metabolism. The bypass of the liver may have evolved to protect this organ from a lipid overload after a meal. The differential handling of medium and longchain fatty acids by intestinal cells can be specifically exploited to provide the liver with highcaloric nutrients in the form of fatty acids. Short and mediumchain fatty acids are not very palatable; however, triacylglycerols synthesized from these fatty acids are quite palatable and can be used as part of the diet. 26.7— Bile Acid Metabolism All bile acids are synthesized within the liver from cholesterol but can be modified by bacterial enzymes in the intestinal lumen. Primary bile acids synthesized by the liver are cholic and chenodeoxycholic (or chenic) acid. The secondary bile acids are derived from the primary bile acids by bacterial dehydroxylation in position 7 of the ring structure, resulting in deoxycholate and lithocholate, respectively (Figure 26.35). Primary and secondary bile acids are reabsorbed by the intestine into the portal blood, taken up by the liver, and then resecreted into bile. Within the liver, primary as well as secondary bile acids are linked to either glycine or Figure 26.35 Bile acid metabolism in the rat. Green and black arrows indicate reactions catalyzed by liver enzymes; red arrows indicate those of bacterial enzymes within the intestinal lumen. (NH—), glycine or taurine conjugate of the bile acids. Page 1084 taurine via an isopeptide bond. These derivatives are called glyco and tauroconjugates, respectively, and constitute the forms that are secreted into bile. With the conjugation, the carboxyl group of the unconjugated acid is replaced by an even more polar group. The pK values of the carboxyl group of glycine and of the sulfonyl group of taurine are lower than that of unconjugated bile acids, so that conjugated bile acids remain ionized over a wider pH range (see Table 26.10). The conjugation is partially reversed within the intestinal lumen by hydrolysis of the isopeptide bond. The total amount of conjugated and unconjugated bile acids secreted per day by the liver is 16–70 g for an adult. As the total body pool is only 3–4 g, bile acids have to recirculate 5–14 times each day between the intestinal lumen and the liver. Reabsorption of bile acids is important to conserve the pool. Most of the uptake is probably by passive diffusion along the entire small intestine. In addition, the lower ileum contains a specialized Na+bile acid cotransport system for concentrative reuptake. Thus during a meal, bile acids from the gallbladder and liver are released into the lumen of the upper small intestine, pass with the chyme down the small intestinal lumen, are reabsorbed by the epithelium of the lower small intestine into the portal blood, and are then extracted from the portal blood by the liver parenchymal cells. The process of secretion and reuptake is referred to as the enterohepatic circulation (Figure 26.36). Reabsorption of bile acids by the intestine is quite efficient as only about 0.5 g of bile acids escapes reuptake each day and is secreted with the feces. Serum levels of bile acids normally vary with the rate of reabsorption and therefore are highest during a meal. Cholate, deoxycholate, chenodeoxycholate, and their conjugates continuously participate in the enterohepatic circulation. In contrast, most of the lithocholic acid that is produced by bacterial enzymes is sulfated during the next passage through the liver. The sulfate ester of lithocholic acid is not a substrate for the bile acid transport system in the ileum and therefore is excreted in the feces. Figure 26.36 Enterohepatic circulation of bile acids. Redrawn from Clark, M. L., and Harries, J. T. In: I. McColl and G. E. Sladen (Eds.), Intestinal Absorption in Man. New York: Academic Press, 1975, p. 195.