Measurement of bile acid synthesis by 14CO2: the metabolism of propionyl CoA.
The relationship between 14CO2 evolution from the catabolism of [26 or 2714C] cholesterol to bile acids was studied in rats with biliary fistulae. When equal quantities of [26 or 2714C] cholesterol and [414C] cholesterol were administered, there was a significant linear relationship between 14CO2 expiration in the breath and [414C] bile acid excreted in the bile. Bile acid synthesis calculated as the ratio of 14CO2: molar specific activity of biliary cholesterol correlated highly with biliary bile acid excretion in the bile acid depleted rat. Phenobarbital, a known inducer of gamma-amino levulenic acid formation from succinyl CoA did not alter the relationship between the 14CO2 estimation of bile acid synthesis and biliary bile acid excretion, indicating that the relationship between [26 or 2714C] cholesterol side chain cleavage and 14CO2 formation was not altered. Phenobarbital, however, did cause a reduction in bile acid synthesis measured by 14CO2 evolution and by biliary bile acid excretion. The 14CO2 method underestimated bile acid excretion. 8.7% in untreated and phenobarbital treated rats respectively. Since 11% of the radioactivity which was expired as 14CO2 was isolated as bile acids, radioactivity cleaved as [1 or 314C] propionyl CoA may enter cholesterol-bile acid biosynthesis resulting in the underestimation of bile acid synthesis. To test whether radioactivity from propionyl CoA enters steroid biosynthesis [114C] propionate and [214C] propionate were given to untreated biliary fistula rats and the biliary lipids excreted in 60 hours were analyzed. Incorporation of radioactivity into cholesterol and bile acids was greater after the administration of [214C] propionate than after [114C] propionate than after [114C] propionate, suggesting that radioactivity from propionyl CoA may enter steroid biosynthesis by metabolic events in which the methylene and carboxyl carbon atoms are differentiated. Although the use of 14CO2 expiration from [26 or 2714C] cholesterol catabolism underestimates the rate of bile acid synthesis, it should have many applications because of the constant relationship between 14CO2 formation and cholesterol side chain cleavage.
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002245:Carbon Dioxide / Q000378:metabolism; D002404:Catheterization; D002635:Chenodeoxycholic Acid / Q000096:biosynthesis; D002784:Cholesterol / Q000378:metabolism*; D002793:Cholic Acids / Q000096:biosynthesis; D003065:Coenzyme A / Q000378:metabolism*; D005260:Female; D010634:Phenobarbital / Q000494:pharmacology; D011422:Propionates / Q000378:metabolism*; D051381:Rats
D001647:Bile Acids and Salts; D002793:Cholic Acids; D011422:Propionates; D002635:Chenodeoxycholic Acid; D002245:Carbon Dioxide; D002784:Cholesterol; D003065:Coenzyme A; D010634:Phenobarbital