7-ALPHA-HYDROXYLATION OF 27-HYDROXYCHOLESTEROL IN HUMAN LIVER-MICROSOMES

Human liver microsomes were found to catalyze 7alpha-hydroxylation of 27-hydroxycholesterol at a rate of up to about 0.2 nmol/mg protein per min. The product of the reaction, 5-cholestene-3beta,7alpha,27-triol, was identified by means of combined gas chromatography-mass spectrometry. Liver microsomes from two patients with an upregulated cholesterol 7alpha-hydroxylase, did not have higher 7alpha-hydroxylase activity towards 27-hydroxycholesterol than those from untreated patients, suggesting that the 7alpha-hydroxylase active towards 27-hydroxycholesterol is not the same as that active towards cholesterol. The mitochondrial fraction of liver from untreated patients and patients treated with cholestyramine, had neglible 7alpha-hydroxylase activity towards 27-hydroxy-cholesterol less than 0.01 nmol/mg protein per min). The results are in accord with the possibility that there is a pathway to bile acids in human liver in which the first step is a 27-hydroxylation of cholesterol.