The major metabolites of ursodeoxycholic acid in human urine are conjugated with N-acetylglucosamine.
Ursodeoxycholic acid (750 mg/day) was administered orally to ten healthy subjects over a period of 10 days; 24 hr urine samples were collected the day before and on the last day of the study. Urinary bile acids were extracted, separated into groups of conjugates and analyzed by gas chromatography-mass spectrometry and fast atom bombardment mass spectrometry. Excretion of ursodeoxycholic acid rose from 70 to 2,915 micrograms/24 h. The highest increase was observed among N-acetylglucosamine conjugates, 90% of which constituted the previously unknown double conjugate of ursodeoxycholic acid with N-acetylglucosamine and glycine. Excretion of isoursodeoxycholic acid increased from 50 to 738 micrograms/24 h. This isomerization product of ursodeoxycholic acid was excreted almost exclusively as N-acetylglucosamine conjugate. In total, N-acetylglucosamine conjugates constituted 50% of urinary metabolites of ursodeoxycholic acid. In addition, metabolites of ursodeoxycholic acid hydroxylated at carbon atoms 1, 6, 22 and possibly 21 were observed. These compounds were also found as conjugates with N-acetylglucosamine. Their formation from ursodeoxycholic acid was definitely demonstrated by 13C-labeling after giving [24-13C]ursodeoxycholic acid to one of the healthy subjects and to a patient with extrahepatic cholestasis in whom hydroxylation of ursodeoxycholic acid at C-23 was also observed. The patient was also found to excrete the double conjugate of ursodeoxycholic acid with N-acetylglucosamine and taurine. The N-acetylglucosaminidation of ursodeoxycholic acid in vivo was shown to occur at C-7.(ABSTRACT TRUNCATED AT 250 WORDS)
Marschall
H U
HU
Department of Internal Medicine III, Aachen University of Technology, Germany.
Griffiths
W J
WJ
Götze
U
U
Zhang
J
J
Wietholtz
H
H
Busch
N
N
Sjövall
J
J
Matern
S
S
D000117:Acetylglucosamine / Q000652:urine*; D000328:Adult; D001651:Cholestasis, Extrahepatic / Q000652:urine; D002849:Chromatography, Gas; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006900:Hydroxylation; D007536:Isomerism; D008297:Male; D012016:Reference Values; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014580:Ursodeoxycholic Acid / Q000652:urine*
D014580:Ursodeoxycholic Acid; D000117:Acetylglucosamine