Effect of biliary obstruction on 26-hydroxylation of C27-steroids in bile acid synthesis.

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.