Bacterial deconjugation and enterohepatic circulation of norursocholic acid conjugates in rats.
Experiments were performed to define the metabolism of norusocholic acid (nUC) conjugates and to quantify to what extent the bile acid pool can be enriched in these bile acids. In vitro incubations of norusocholylglycine (nUCG) and -taurine (nUCT) with small intestinal or cecal content showed deconjugation with only cecal content. Cholylglycine (CG) was deconjugated by small intestinal and cecal content. Infusion of nUCG and CG showed that only a small proportion of nUCG was deconjugated after 24 h of enterohepatic circulation, whereas all CG was deconjugated. When nUCT was administered orally, deconjugation was shown to take place mainly in the cecum. Chronic feeding of nUCT enriched the bile acid pool with only 20% nUCT. We conclude that nUC conjugates are deconjugated primarily by bacteria in the cecum and colon, in contrast to CG, which, in addition to cecum and colon, is deconjugated in the distal small intestine. nUCT and its metabolites do not enrich in the circulating bile acid pool mainly for the following reasons: 1) nUC conjugates have a low affinity for the ileal transport system; 2) nUC, even if formed by deconjugation, is not passively absorbed at a sufficient rate; 3) the small amount of norursodeoxycholic acid formed from nUC is glucuronidated in the liver and glucuronide conjugates do not undergo enterohepatic circulation; and 4) nUC conjugates do not suppress bile acid biosynthesis.
Lillienau
J
J
Department of Medical and Physiological Chemistry, University of Lund, Sweden.
Borgström
B
B
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D019826:Cholic Acid; D002793:Cholic Acids / Q000378:metabolism; D003227:Conjugation, Genetic; D004032:Diet; D004064:Digestive System / Q000378:metabolism* / Q000382:microbiology; D007700:Kinetics; D008099:Liver / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001647:Bile Acids and Salts; D002793:Cholic Acids; D010743:Phospholipids; D019826:Cholic Acid