JBC, Vol. 251, Issue 20, 6308-6314, Oct, 1976
Quantitative aspects of the conversion of 5 beta-cholestane intermediates to bile acids in man
C. C. Schwartz, B. I. Cohen, Z. R. Vlahcevic, D. H. Gregory, L. G. Halloran, T. Kuramoto, E. H. Mosbach and L. Swell
The in vivo conversion of several 5 beta-cholestane intermediates to
primary bile acids was investigated in three patients with total biliary
diversion. The following compounds were administered intravenously: 5
beta-[G-3H]-cholestane-3 alpha, 7 alpha-diol, 5 beta-[G-3H]cholestane-3
alpha, 7alpha, 26-triol, and 5 beta-[24-14C]cholestane-3 alpha, 7
alpha-25-triol. Bile was then collected quantitatively at frequent
intervals for the next 21 to 28 h. The administered 5
beta-[G-3H]cholestane-3alpha, 7alpha, 26-triol was found to be efficiently
converted to cholic and chenodeoxycholic acids in two patients; 61 and 75%
of the administered label was found in primary bile acids. The proportion
of labeled cholic to chenodeoxycholic acid was 1.20 and 1.02 in the bile of
these patients, indicating that the C-26 triol was efficiently converted to
cholic acid. The ratio of cholic to chenodeoxycholic acid (mass) in the
bile of these patients was 1.23 and 2.32. The 5 beta-cholestane-3alpha,
7alpha-diol intermediate was also efficiently converted (71%) to both
primary bile acids. The cholic to chenodeoxycholic acid ratios by mass and
label were similar (2.97 versus 2.23). By contrast, the
5beta-cholestane-3alpha, 7alpha, 25-triol was poorly converted to bile
acids in three patients. Following the administration of this compound
almost all of the administered radioactivity found in the bile acid
fraction was in cholic acid (5 to 19%) and very little (less than 5%) was
found in chenodeoxycholic acid. These findings indicate that ring
hydroxylation at position 12 is not materially hindered by the presence of
a hydroxyl group on the side chain at C-26 in patients with biliary
diversion. The labeled C-26-triol which was efficiently converted to both
primary bile acids in a proportion similar to that which was observed for
the bile acids synthesized by the liver suggests that this 5beta-cholestane
derivative may be a major intermediate in the synthesis of both cholic and
chenodeoxycholic acids.
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