The plasma level of 7 alpha-hydroxy-4-cholesten-3-one reflects the activity of hepatic cholesterol 7 alpha-hydroxylase in man.
Circulating levels of 7 alpha-hydroxy-4-cholesten-3-one have been compared with activities of the rate-limiting enzyme in bile acid synthesis, microsomal cholesterol 7 alpha-hydroxylase, measured in liver biopsies obtained from patients undergoing surgery for gallstone disease. Some patients were treated with cholestyramine or bile acids prior to operation in order to alter the feed-back inhibition of the enzyme. The levels of the sterol were similar in untreated patients and in patients treated with ursodeoxycholic acid (median concentration 17 and 13 ng/ml, respectively), and so were the activities of the enzyme (median activity 7.0 and 5.5 pmol/min/mg protein, respectively). The sterol levels and enzyme activities were significantly increased in patients treated with cholestyramine (91 ng/ml and 45 pmol/min/mg protein) and decreased in patients treated with chenodeoxycholic acid (less than 2.0 ng/ml and 0.7 pmol/min/mg protein). There was a strong positive correlation (r = 0.90, P less than 0.00001) between levels of 7 alpha-hydroxy-4-cholesten-3-one in plasma and the activities of cholesterol 7 alpha-hydroxylase in the whole patient group. The results show that analysis of 7 alpha-hydroxy-4-cholesten-3-one in plasma is a sensitive and convenient method to determine relative rates of bile acid production in man.
Axelson
M
M
Department of Clinical Chemistry, Karolinska Hospital, Stockholm, Sweden.
Björkhem
I
I
Reihnér
E
E
Einarsson
K
K
D000328:Adult; D002635:Chenodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use; D002769:Cholelithiasis / Q000188:drug therapy / Q000201:enzymology; D002783:Cholestenones / Q000097:blood; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use
D002783:Cholestenones; D002635:Chenodeoxycholic Acid; D002792:Cholestyramine Resin; C002656:7 alpha-hydroxy-4-cholesten-3-one; D014580:Ursodeoxycholic Acid; D002790:Cholesterol 7-alpha-Hydroxylase