title: An in vivo evaluation of the quantitative significance of several potential pathways to cholic and chenodeoxycholic acids from cholesterol in man.
abstract: The present study was designed to obtain more definitive information in man on the metabolic pathways to chenodeoxycholic acid and to cholic acid via a pathway not involving an initial 7 alpha-hydroxylation of cholesterol. Four bile fistula patients were administered consecutively two or more of the following 3H-labeled bile acid intermediates: 7 alpha-hydroxycholesterol, 7 alpha-hydroxy-4-cholesten-3-one, 5 beta-cholestane 3 alpha,7 alpha,26-triol, 26-hydroxycholesterol,7 alpha,26-dihydroxy-4-cholesten-3-one, and 5-cholestene-3 beta,12 alpha-diol. Both 7 alpha-hydroxy[7 beta-3H]cholesterol and 7 alpha-hydroxy-4-[6 beta-3H]cholesten-3-one were efficiently converted to bile acids and preferred chenodeoxycholic acid over cholic acid. The specific activity time curves indicated that a portion of cholic acid synthesis did not pass through 7 alpha-hydroxycholesterol. [3H]26-Hydroxycholesterol and [3H]-5-cholestene 3 beta,12 alpha-diol, two potential intermediates of this bypass pathway to cholic acid, were poorly converted to primary bile acids (10 to 27%). The [3H]26-hydroxycholesterol preferred chenodeoxycholic over cholic acid by about 4 to 1. The [3H]5-cholestene 3 beta,12 alpha-diol formed cholic acid in low yield (10 to 20%). It is concluded that pathways to primary acids from cholesterol through 26-hydroxycholesterol and 5-cholestene 3 beta,12 alpha-diol are probably of minor quantitative significance. A selective pathway to chenodeoxycholic acid via 26-hydroxylation of 7 alpha-hydroxy-4-cholesten-3-one was also investigated. The 5 beta-cholestane 3 alpha,7 alpha,26-triol was converted in about equal amounts to cholic and chenodeoxycholic acids. The 7 alpha-hydroxy-4-cholesten-3-one was also efficiently converted to both bile acids but preferred chemodeoxycholic acid. The most efficient precursor of chenodeoxycholic acid was 7 alpha,26-dihydroxy-4-cholesten-3-one, which was efficiently converted to primary bile acids; chenodeoxycholic acid was preferred over cholic acid by approximately 7 to 1. These findings suggest the presence of a major pathway to chenodeoxycholic acid via the 26-hydroxylation of 7 alpha-hydroxy-4-cholesten-3-one and intermediate formation of 7 alpha,26-dihydroxy-4-cholesten-3-one.
mesh_terms: D001646:Bile / Q000378:metabolism; D002635:Chenodeoxycholic Acid / Q000378:metabolism; D002777:Cholestanols; D002783:Cholestenones; D002784:Cholesterol / Q000378:metabolism*; D002793:Cholic Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols; D007700:Kinetics
chemical_list: D002777:Cholestanols; D002783:Cholestenones; D002793:Cholic Acids; D006888:Hydroxycholesterols; D002635:Chenodeoxycholic Acid; C011722:cholestane-3,7,26-triol; C002656:7 alpha-hydroxy-4-cholesten-3-one; C025573:7 alpha,26-dihydroxy-4-cholesten-3-one; C025574:5-cholestene-3 beta,12 alpha-diol; D002784:Cholesterol