12 alpha-hydroxylase activity in human liver and its relation to cholesterol 7 alpha-hydroxylase activity.
Interruption of the enterohepatic circulation by cholestyramine causes a several-fold increase in bile acid synthesis, reflected in a stimulation of cholesterol 7 alpha-hydroxylase activity; the synthesis of cholic acid being stimulated to a greater extent than chenodeoxycholic acid. It is not known if this preferential increase in cholic acid is due to an increase of the 12 alpha-hydroxylase activity. The present study aimed at investigating the 12 alpha-hydroxylase activity and its relation to cholesterol 7 alpha-hydroxylase activity in liver microsomes of patients with different levels of cholesterol 7 alpha-hydroxylase activity. Liver biopsies were obtained from four gallstone-free patients, and seven untreated and two cholestyramine-treated gallstone patients undergoing cholecystectomy, and four patients with Crohn's disease undergoing intestinal resection. The combined group of cholestyramine-treated and ileum-resected patients had four times higher cholesterol 7 alpha-hydroxylase activity and two times higher 12 alpha-hydroxylase activity than the other patients. A positive correlation was obtained between cholesterol 7 alpha-hydroxylase activity and 12 alpha-hydroxylase activity (r = +0.69; n = 16). These results indicate that the increased ratio between the synthesis of cholic acid and chenodeoxycholic acid during cholestyramine treatment is due to a compensatory increase of the 12 alpha-hydroxylase activity.
Einarsson
K
K
Department of Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
Akerlund
J E
JE
Reihnér
E
E
Björkhem
I
I
D000328:Adult; D002769:Cholelithiasis / Q000188:drug therapy / Q000201:enzymology; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000627:therapeutic use; D003424:Crohn Disease / Q000201:enzymology / Q000601:surgery; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008875:Middle Aged; D013253:Steroid 12-alpha-Hydroxylase / Q000378:metabolism*
D002792:Cholestyramine Resin; D002790:Cholesterol 7-alpha-Hydroxylase; D013253:Steroid 12-alpha-Hydroxylase