7α‐Hydroxylation of 26‐hydroxycholesterol, 3β‐hydroxy‐5‐cholestenoic acid and 3β‐hydroxy‐5‐cholenoic acid by cytochrome P‐450 in pig liver microsomes

Abstract
Pig liver microsomes were found to catalyze the 7α‐hydroxylation of several potential bile acid precursors besides cholesterol. 26‐Hydroxycholesterol, 3β‐hydroxy‐5‐cholestenoic acid and 3β‐hydroxy‐5‐cholenoic acid were all efficiently converted into the 7α‐hydroxylated products. Two cytochrome P‐450 fractions showing 7α‐hydroxylase activity could be isolated. One fraction catalyzed 7α‐hydroxylation of 26‐hydroxycholesterol. 3β‐hydroxy‐5‐cholestenoic acid and 3β‐hydroxy‐5‐cholenoic acid but was inactive towards cholesterol. The other fraction catalyzed 7α‐hydroxylation of cholesterol in addition to the other substrates. 26‐Hydroxycholesterol in equimolar concentration did not inhibit the cholesterol 7α‐hydroxylase activity of this fraction. It is concluded that liver microsomes contain a cytochrome P‐450 catalyzing 7α‐hydroxylation of 26‐hydroxycholesterol, 3β‐hydroxy‐5‐cholestenoic acid and 3β‐hydroxy‐5‐cholenoic acid. The results indicate that this cytochrome P‐450 is different from that catalyzing 7α‐hydroxylation of cholesterol.

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