Assay of bile acids in biological samples

Abstract

Bile acids are steroid carboxylic acids containing 22–28 carbon atoms (Haslewood, 1967, 1978). The common naturally occurring bile acids are saturated C24 acids. Bile acids are found only in vertebrate species, and in the vertebrates so far examined the biosynthesis of bile acids from cholesterol takes place in the liver. In man, the major pathway of bile acid synthesis begins with 7α-hydroxylation of the cholesterol ring nucleus and ends with oxidation of the cholesterol side chain. Thus there are normally two primary bile acids in man: cholic acid and chenodeoxycholic acid (Figure 9.1). A minor pathway of bile acid synthesis in the human liver begins with oxidation of the cholesterol side chain and ends with hydroxylation of the ring nucleus. The bile acids produced by this pathway include 3β-hydroxy-5-cholen-24-oic acid, lithocholic acid and chenodeoxycholic acid (Mitropoulos and Myant, 1967; Javitt, 1972). The secondary bile acids in man are deoxycholic and lithocholic acids, which are formed from the primary bile acids by the action of intestinal organisms normally present in the terminal ileum, caecum and colon. Bile acids are conjugated in the human liver with taurine or glycine before they are secreted via the biliary canaliculi into the bile. Bile is concentrated in the gallbladder, which discharges its contents on contraction into the duodenum. Bacterial action on bile acids in the intestine usually begins with de-conjugation and includes 7α-dehydroxylation. Bacterial degradation of bile acids may also include dehydration, dehydrogenation and epimerisation, as a result of which there are a large number of bacterially derived bile acid metabolites. The best known of these is ursodeoxycholic acid (3α,7β-dihydroxy-5β-cholan-24-oic acid), the 7β epimer of chenodeoxycholic acid. The majority of bile acids in the intestinal lumen are absorbed and returned via the portal vein to the liver. They are then re-excreted as conjugated bile acids in bile. At several stages in their enterohepatic circulation the bile acids perform essential physiological functions peculiar to their chemical structure (Heaton, 1972). In addition to conjugation some bile acids, particularly secondary bile acids, may be sulphated or glucuronidated in the liver or kidney.