Journal of Lipid Research, Vol 19, 237-243, Copyright © 1978 by Lipid Research, Inc.
Effect of biliary obstruction on 26-hydroxylation of C27-steroids in bile acid synthesis
J Gustafsson
The effect of biliary obstruction on side chain hydroxylations in the
biosynthesis and metabolism of bile acids was studied in the rat. For
comparison, several other hydroxylation reactions in bile acid biosynthesis
and metabolism were assayed. Biliary obstruction inhibited microsomal
26-hydroxylation of 5beta-cholestane-3alpha,7alpha-diol and microsomal 25-
and 26-hydroxylation of 5beta-cholestane-3alpha,7alpha- 12alpha-triol.
Microsomal 7alpha-hydroxylation of cholesterol and 6beta- hydroxylation of
lithocholic acid acid increased significantly, whereas the increase in
microsomal 12alpha-hydroxylation of 5beta-cholestane- 3alpha,7alpha-diol
was less. Mitochondrial 26-hydroxylation of cholesterol,
5-cholestene-3beta,7alpha-diol, and 7alpha-hydroxy-4- cholesten-3-one was
stimulated, whereas 26-hydroxylation of 5beta-
cholestane-3alpha,7alpha-diol was not affected and that of 5beta-
cholestane-3alpha,7alpha,12alpha-triol was markedly inhibited. The results
indicate that mitochondrial 26-hydroxylation, particularly of substrates
that primarily are precursors of chenodeoxycholic acid, plays a more
important role in bile acid biosynthesis under conditions of biliary
obstruction than under normal conditions.