Bile acid N-acetylglucosaminidation : in vivo and in vitro evidence for a selective conjugation reaction of 7β-hydroxylated bile acids in humans

• Published in: The Journal of clinical investigation 1992-06, Vol.89 (6), p.1981-1987
• Main Authors: MARSCHALL, H.-U, MATERN, H, WIETHOLTZ, H, EGESTAD, B, MATERN, S, SJÖVALI, J
• Format: Article
• Language: English
• Subjects: Acetylglucosamine - metabolism; Administration, Oral; Bile Acids and Salts - administration & dosage; Bile Acids and Salts - metabolism; Biological and medical sciences; Chenodeoxycholic Acid - metabolism; Cholestasis - metabolism; Deoxycholic Acid - metabolism; Fundamental and applied biological sciences. Psychology; Glycosides - urine; Humans; Hydroxylation; Liver Diseases - metabolism; Liver. Bile. Biliary tracts; Mass Spectrometry; Ursodeoxycholic Acid - metabolism; Vertebrates: digestive system
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci115806

The aim of this study was to define whether N-acetylglucosaminidation is a selective conjugation pathway of structurally related bile acids in humans. The following bile acids released enzymatically from N-acetylglucosaminides were identified: 3 alpha,7 beta-dihydroxy-5 beta-cholanoic (ursodeoxycholic), 3 beta, 7 beta-dihydroxy-5 beta-cholanoic (isoursodeoxycholic), 3 beta,7 beta-dihydroxy-5 alpha-cholanoic (alloisoursodeoxycholic), 3 beta,7 beta-dihydroxy-5-cholenoic, 3 alpha,7 beta,12 alpha-trihydroxy-5 beta-cholanoic, and 3 alpha,6 alpha,7 beta-trihydroxy-5 beta-cholanoic acids. The selectivity of conjugation was studied by administration of 0.5 g ursodeoxycholic (UDCA) or hyodeoxycholic (HDCA) acids, labeled with 13C, to patients with extrahepatic cholestasis, and of 0.5 g of 13C-labeled chenodeoxycholic acid (CDCA) to patients with extra- or intrahepatic cholestasis. After administration of [24-13C]-CDCA, labeled glucosides, and the glucuronide of CDCA were excreted in similar amounts. Labeled N-acetylglucosaminides of UDCA and isoUDCA were also formed. When [24-13C]-UDCA was given, 13C-label was detected in the N-acetylglucosaminide, the glucosides, and the glucuronide of UDCA, and in the N-acetylglucosaminide of isoUDCA. In the patient studied, 32% of the total UDCA excreted in urine was conjugated with N-acetylglucosamine. In contrast, 96% of the excreted amount of [24-13C]HDCA was glucuronidated, and 13C-labeled glucosides but no N-acetylglucosaminide were detected. The selectivity of N-acetylglucosaminidation towards bile acids containing a 7 beta-hydroxyl group was confirmed in vitro using human liver and kidney microsomes and uridine diphosphate glucose (UDP)-N-acetylglucosamine. These studies show that N-acetylglucosaminidation is a selective conjugation pathway for 7 beta-hydroxylated bile acids.