Rabbit liver contains one major sterol 12α-hydroxylase with broad substrate specificity

Conversion of cholesterol into cholic acid in mammalian liver requires a 12 alpha-hydroxylation step. Results have been presented suggesting that two different enzymes are involved in this hydroxylation with different activities towards the two steroids believed to be the physiological substrates for the enzyme, 7 alpha-hydroxy-4-cholesten-3-one and 5 beta-cholestane-3 alpha,7 alpha-diol. It is shown here that rabbit Liver microsomes and partly purified sterol 12 alpha-hydroxylase as well as COS cells transfected with a cDNA coding for this enzyme are able to catalyze 12 alpha-hydroxylation of the two substrates at similar relative rates. Also 7 alpha-hydroxycholesterol and 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid are 12 alpha-hydroxylated by the three systems. It is concluded that rabbit liver contains one major sterol 12 alpha-hydroxylase with a broad substrate specificity. (C) 1998 Elsevier Science B.V.