Metabolism of lithocholate in healthy man. II. Enterohepatic circulation

Studies were carried out in healthy subjects to characterize the enterohepatic circulation of lithocholate and its metabolites. When mixed with bile and infused into the jejunum, radiolabeled lithocholylglycine was absorbed more rapidly and more efficiently than sulfolithocholylglycine, based on recovery from bile. When these metabolites were administered at 1800 hr in a liquid test meal containing radiolabeled taurocholate as an absorbable marker, 60% of lithocholylglycine was conserved, based on recovery of radioactivity in fasting bile the following morning, but only 20% of sulfolithocholylglycine was conserved. Iotope dilution studies in 4 subjects showed that daily input of lithocholate into the bile acid pool averaged 100 mg per day, about one-third to one-half of the chenodeoxycholic acid synthesis, but the t 1/2 was extremely short (0.74 day). The small lithocholate pool (about 100 mg) could be explained by rapid fecal excretion caused by sulfation which decreases passive absorption in the jejunum and active absorption in the ileum. Experiments with [35S]sulfo- [3H]lithocholylglycine indicated little desulfation during enterohepatic cycling but rapid desulfation in the distal intestine, with absorption of 35S (presumably as sulfate) followed by urinary excretion. A decreasing 35S:3H ratio in bile indicated that some steroid moiety was conserved to be resulfated. These studies indicate that considerable lithocholate is absorbed from the distal intestine in healthy subjects but efficient sulfation results in rapid fecal excretion, so that the total lithocholate pool remains small. A multicompartment model, previously used to describe the metabolism of the steroid and amino acid moieties of the major conjugated biliary bile acids, was extended to encompass lithocholyl conjugates and their sulfates.