The Selective Inhibition of Chenodeoxycholate Synthesis by Cholate Metabolites in Man

Abstract

1. Seven normal volunteers took 0-28--0-42 mmol (100--150 mg) of deoxycholate by mouth. This resulted in a reduced proportion of chenodeoxycholate in bile and an increased proportion of deoxycholate. Cholate was unchanged. 2. Cholate and chenodeoxycholate pools and rats of synthesis were determined in four of the subjects by simultaneously labelling each pool with 14C-labelled bile acids. The chenodeoxycholate pool and rate of synthesis decreased after deoxycholate administration. Cholate synthesis and pool size did not change appreciably. 3. The proportion of deoxycholate in bile samples of sixty-two subjects with intact enterohepatic circulation was found to be inversely related to the proportion of chenodeoxycholate in bile, but not to the cholate. 4. It is suggested that inhibition of chenodeoxycholate synthesis by deoxycholate, the principal bacterial product of cholate, regulates the size of the chenodeoxycholate pool independently of the total amount of bile salt.

Role of primary and secondary bile acids as feedback inhibitors of bile acid synthesis in the rat in vivo.

“…During partial or total interruption of the enterohepatic circulation of bile acids with cholestyramine or bile diversion bile acid synthesis increased (9)(10)(11)(12) due to apparent derepression. These data obtained in rats were confirmed by work in primates (13,14) and in humans (15)(16)(17)(18)(19)(20)(21)(22)(23) using both bile acid depletion and administration.…”

“…In the hamster deoxycholic acid appears to be extremely toxic (45), whereas in the baboon deoxycholic acid was the single most potent feedback inhibitor of bile acid synthesis (14). In man, most (16,17,19) but not all (34) of the available evidence supports a role for deoxycholic acid as feedback inhibitor. It has also been suggested that this bile acid is instrumental not only in regulating bile acid pool sizes but also in affecting biliary cholesterol saturation (46)(47)(48)(49).…”

Effect of Oat Bran on Lithogenic Index of Bile and Bile Acid Metabolism

“…Pre vious studies [19,20] have demonstrated that a change in deoxycholate is accompa nied by a reciprocal change in chenodeoxycholate. possibly because chenodeoxycholate synthesis is sensitive to inhibition by deoxy cholate [21], However, it should be noted that this reciprocal effect has not been con firmed in another study [22] which still leaves the problem unsettled.…”

Effect of Selective Proximal and Truncal Vagotomy on Canine Gallbladder Bile Composition

“…In this respect a species difference exists between dog and man. In man no correlation could be demonstrated between the percentages of deoxycholic acid and of cholic acid in bile [Pomare and Low-Beer, 1975]. These authors, however, noted an inverse relationship between deoxycholic acid an chenodeoxycholic acid in human bile.…”