Altered metabolism of bile acids in cholestasis: determination of 1 beta- and 6 alpha-hydroxylated metabolites

Trihydroxy and tetrahydroxy bile acid metabolites substituted at the C-1 or C-6 position were studied using the urine, serum and liver tissue from sixteen patients with cholestatic liver diseases. Following extraction, isolation and hydrolysis, bile acids were converted into the dimethylethylsilyl derivatives and assayed by capillary gas chromatography-mass spectrometry. Five 1 beta-hydroxylated bile acids, viz. 1 beta,3 alpha,12 alpha-trihydroxy-, 1 beta,3 alpha,7 alpha-trihydroxy-, 1 beta,3 alpha,7 beta-trihydroxy-, 1 beta,3 alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholanoic acids and an epimer of the first compound, and two 6 alpha-hydroxylated bile acids, viz. 3 alpha,6 alpha,7 alpha-trihydroxy-, 3 alpha,6 alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholanoic acids, were completely or partially identified. Large amounts of 1 beta-hydroxylated and 6 alpha-hydroxylated bile acids were found in the urine, whereas only trace amounts were detected in the serum and liver tissue. These findings indicate that altered metabolism, such as 1 beta- or 6 alpha-hydroxylation of bile acids, is enhanced in cholestasis, and that the resulting hydroxylated metabolites are eliminated in the urine.