Esterified and total 7 alpha-hydroxycholesterol in human serum as an indicator for hepatic bile acid synthesis.
Serum levels of 7 alpha-hydroxycholesterol and activities of hepatic microsomal cholesterol 7 alpha-hydroxylase in surgical patients were analyzed by capillary gas-liquid chromatography-selected ion monitoring technique using a new internal standard, 5 alpha-cholestane-3 beta, 7 beta-diol. We found that concentrations of 7 alpha-hydroxycholesterol obtained after alkaline hydrolysis were higher than those without alkaline hydrolysis, indicating that a considerable amount of 7 alpha-hydroxycholesterol in human serum is present in esterified form. Esterified 7 alpha-hydroxycholesterol could also be quantitatively hydrolyzed with cholesterol esterase, suggesting that fatty acid is bound at the 3 beta-position of the cholestenediol. The serum levels of esterified and free 7 alpha-hydroxycholesterol in patients with cholelithiasis were 198.0 +/- 90.3 and 48.3 +/- 19.8 pmol/ml (mean +/- SD), respectively, and were similar to those in patients without hepatobiliary diseases. After treatment with chenodeoxycholic acid (300 mg per day) for 7 to 10 days, esterified and free 7 alpha-hydroxycholesterol levels decreased to 64.9 +/- 33.6 and 20.5 +/- 11.1 pmol/ml, respectively. Activity of cholesterol 7 alpha-hydroxylase was also inhibited. Treatment with ursodeoxycholic acid (600 mg per day) for 7 to 10 days had no inhibitory effect on serum 7 alpha-hydroxycholesterol levels and the enzyme activity. In all groups, high correlations were found between the activity of cholesterol 7 alpha-hydroxylase and serum levels of 7 alpha-hydroxycholesterol: free (r = 0.71, n = 38, P less than 0.001); esterified (r = 0.87, n = 38, P less than 0.001); total (r = 0.87, n = 38, P less than 0.001). Esterified and total 7 alpha-hydroxycholesterol was more highly correlated with the enzyme activity than the free form. We conclude that a significant amount of 3 beta-acyl esters of 7 alpha-hydroxycholesterol is present in human serum and that serum levels of esterified and/or total 7 alpha-hydroxycholesterol are likely to reflect the activity of hepatic cholesterol 7 alpha-hydroxylase and thus the amount of primary bile acids synthesized in the liver.
Oda
H
H
Department of Surgery I, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Yamashita
H
H
Kosahara
K
K
Kuroki
S
S
Nakayama
F
F
D000328:Adult; D000368:Aged; D001646:Bile / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D004951:Esterification; D005260:Female; D006801:Humans; D006868:Hydrolysis; D006888:Hydroxycholesterols / Q000097:blood*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008875:Middle Aged; D002787:Sterol Esterase / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000494:pharmacology
D006888:Hydroxycholesterols; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; D002787:Sterol Esterase