Bile acid N-acetylglucosaminidation. In vivo and in vitro evidence for a selective conjugation reaction of 7 beta-hydroxylated bile acids in humans.
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.
Marschall
H U
HU
Department of Internal Medicine III, Aachen University of Technology, Germany.
Matern
H
H
Wietholtz
H
H
Egestad
B
B
Matern
S
S
Sjövall
J
J
D000117:Acetylglucosamine / Q000378:metabolism*; D000284:Administration, Oral; D001647:Bile Acids and Salts / Q000008:administration & dosage / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000378:metabolism; D002779:Cholestasis / Q000378:metabolism; D003840:Deoxycholic Acid / Q000378:metabolism; D006027:Glycosides / Q000652:urine; D006801:Humans; D006900:Hydroxylation; D008107:Liver Diseases / Q000378:metabolism; D013058:Mass Spectrometry; D014580:Ursodeoxycholic Acid / Q000378:metabolism
D001647:Bile Acids and Salts; D006027:Glycosides; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; C010471:hyodeoxycholic acid; D000117:Acetylglucosamine