Bile acid metabolism in cirrhosis. VII. Evidence for defective feedback control of bile acid synthesis.
The present report has been directed toward providing additional information on the major defects in the bile acid pathways present in patients with cirrhosis and its relevance to the problem of how bile acid synthesis is regulated in man. An unusual patient with severe liver disease and a completely broken enterohepatic circuit was studied. The synthesis of cholic and chenodeoxycholic acids was examined over a 5-d period. The secretion rats and the incorporation of [3H]7 alpha-hydroxycholesterol and [3H]26-hydroxycholesterol into both primary bile acids in the cirrhotic bile fistula patient was cross compared to earlier data obtained on patients with and without liver disease and an intact enterohepatic circuit and patients with no liver disease and a bile fistula. The daily synthesis rate of cholic acid increased 7-fold and chenodeoxycholic acid 2-fold in the cirrhotic bile fistula patient. The incorporation of [3H]7 alpha- hydroxycholesterol into bile acids in the cirrhotic bile fistula patient was efficient (75%) and equal to bile fistula patients with no cirrhosis (76%); chenodeoxycholic acid synthesis was favored over cholic acid particularly in the cirrhotic patient. [3H]26-hydroxycholesterol was poorly incorporated in patients with no cirrhosis (25%) and the cirrhotic patient (20%); chenodeoxycholic acid was favored by a wide margin. It is concluded from this and previous reports that the profound reduction in bile acid synthesis present in patients with cirrhosis is not caused singly by a failure in the metabolic pathways from 7 alpha-hydroxycholesterol to cholic and chenodeoxycholic acid (i.e., 12 alpha-hydroxylation step), but rather due to a defect in the feedback control regulating bile acid synthesis.
D001647:Bile Acids and Salts / Q000096:biosynthesis*; D001658:Biliary Fistula / Q000150:complications / Q000378:metabolism; D002635:Chenodeoxycholic Acid / Q000096:biosynthesis; D002793:Cholic Acids / Q000096:biosynthesis; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged
D001647:Bile Acids and Salts; D002793:Cholic Acids; D006888:Hydroxycholesterols; D002635:Chenodeoxycholic Acid