title: Concentration of unsulfated lithocholic acid in portal and systemic venous plasma: evidence that lithocholic acid does not down regulate the hepatic cholesterol 7 alpha-hydroxylase activity in gallstone patients.
abstract: It has been proposed that lithocholic acid may have a physiological role for the regulation of bile acid synthesis in humans. In this study, the portal concentration and hepatic uptake of unsulfated lithocholic acid was determined in 21 gallstone patients-untreated, cholestyramine-treated and chenodeoxycholic acid-treated-at cholecystectomy. Lithocholic acid was analyzed by a combined gas-liquid mass-fragmentographic technique. In most of the patients a liver biopsy was obtained for assay of the cholesterol 7 alpha-hydroxylase activity. The portal venous concentration of unsulfated lithocholic acid averaged 0.32 mumol/l in untreated patients, constituting about 4% of the total bile acids. The apparent hepatic uptake of lithocholic acid averaged 78%, being as high as that of cholic acid. No significant correlation was obtained between the portal venous concentration of unsulfated lithocholic acid and the hepatic cholesterol 7 alpha-hydroxylase activity. This study thus confirms an enterohepatic circulation of lithocholic acid in humans. No evidence was obtained that the portal venous inflow of small amounts of lithocholic acid to the liver is of regulatory importance for the cholesterol 7 alpha-hydroxylase activity.
authors.affiliation: Division of Medicine, Karolinska Institute at Huddinge University Hospital, Stockholm, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Einarsson
authors.forename: G
authors.initials: G
authors.lastname: Alvelius
authors.forename: C G
authors.initials: CG
authors.lastname: Hillebrant
authors.forename: E
authors.initials: E
authors.lastname: Reihnér
authors.forename: I
authors.initials: I
authors.lastname: Björkhem
mesh_terms: D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000097:blood / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000627:therapeutic use; D002769:Cholelithiasis / Q000188:drug therapy / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000627:therapeutic use; D015536:Down-Regulation; D004764:Enterohepatic Circulation; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008095:Lithocholic Acid / Q000097:blood* / Q000378:metabolism; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D011169:Portal Vein
chemical_list: D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D002792:Cholestyramine Resin; D008095:Lithocholic Acid; D002790:Cholesterol 7-alpha-Hydroxylase