Characterisation of bile acid metabolism in man using bile acids labelled with stable isotopes

Abstract

Bile acids are acidic steroids formed in the liver from cholesterol and secreted into bile as their N-glycine or N-taurine conjugates. Their biological and clinical aspects have been thoroughly reviewed (Heaton, 1972; Dietschy, 1972; Nair and Kritchevsky, 1973; Paumgartner, 1977). Bile acids are amphipathic molecules which can disperse lecithin in micellar form, and bile is a concentrated micellar solution containing mixed micelles of bile acids, lecithin and cholesterol. When this mixed bile acid micelle reaches the small intestinal lumen, its composition changes and now the major lipid constituting the mixed micelle is fatty acid (plus some monoglyceride), which derives from pancreatic lipolysis of dietary triglyceride. Micellar solubilisation of the relatively insoluble fatty acid and monoglyceride greatly increases their aqueous concentration and thus accelerates the diffusive flux through the unstirred layer. Most of the bile acids are reabsorbed in the small intestine, especially the terminal ileum, where there is an active transport site. The bile acids return in the portal blood to the liver, where they are efficiently extracted and rapidly secreted into bile. This circulation of bile acids from liver to intestine and back to liver is termed the enterohepatic circulation, and it occurs about twice per meal. A small amount of bile acids are lost from the enterohepatic circulation and are excreted in faeces; the bile acid pool is maintained by hepatic synthesis. There is no urinary loss of bile acids (Figure 17.1). The bile acid conjugates are mostly absorbed in conjugated form from the small intestine, but a small amount of the bile acid conjugates is hydrolysed by bacterial deconjugases, releasing the unconjugated bile acid moiety. Most of this is reabsorbed to return to the liver, where it is reconjugated (Hepner et al., 1973).