Altered bile acid metabolism in liver disease: concurrent occurrence of C-1 and C-6 hydroxylated bile acid metabolites and their preferential excretion into urine.
C-1 and C-6 hydroxylated bile acid metabolites in various biological specimens from subjects with liver disease (cholestasis, liver cirrhosis, chronic hepatitis, acute hepatitis) were determined by gas-liquid chromatography-mass spectrometry. Five C-1 hydroxylated bile acids and nine C-6 hydroxylated bile acids were identified in the urine studied; 1 beta,3 alpha,12 alpha-trihydroxy-, 1 beta,3 alpha,7 alpha-trihydroxy-, 1 beta,3 alpha,7 alpha,12 alpha-tetrahydroxy-, 3 alpha,6 alpha,7 alpha-trihydroxy-, and 3 alpha,6 alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholanoic acids were found as the major components. Most of the 1 beta- and 6 alpha-hydroxylated bile acids were excreted into urine in the nonsulfate-nonglucuronide form. The amounts in the urine were greater than those found in the bile, portal and peripheral venous sera, and liver specimens. The biliary excretion and hepatic extraction of 1 beta-hydroxylated metabolites were more impaired and less efficient than for cholic acid. These findings suggested that hepatic 1 beta- or 6 alpha-hydroxylation of bile acids occurred concurrently in the patients with liver disease and that the resulting hydroxylated metabolites were efficiently excreted in the nonsulfate-nonglucuronide form into urine rather than into bile.
Shoda
J
J
Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Tanaka
N
N
Osuga
T
T
Matsuura
K
K
Miyazaki
H
H
D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000378:metabolism* / Q000652:urine; D002779:Cholestasis / Q000378:metabolism / Q000652:urine; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006505:Hepatitis / Q000378:metabolism / Q000652:urine; D006801:Humans; D006900:Hydroxylation; D008103:Liver Cirrhosis / Q000378:metabolism / Q000652:urine; D008107:Liver Diseases / Q000378:metabolism* / Q000652:urine; D008297:Male; D008875:Middle Aged
D001647:Bile Acids and Salts