Identification of (24E)-3 alpha,7 alpha-dihydroxy-5 beta-cholest-24-enoic acid and (24R,25S)-3 alpha,7 alpha,24-trihydroxy-5 beta-cholestanoic acid as intermediates in the conversion of 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid to chenodeoxycholic acid in rat liver homogenates.
Studies of chemical structure of the intermediates in the biosynthetic sequence between 3 alpha,7 alpha-dihydroxy-5 beta-cholestanoic acid (DHCA) and chenodeoxycholic acid have been undertaken. Radiolabeled DHCA was incubated with a rat liver preparation. The reaction products were converted to the p-bromophenacyl esters, and analyzed by reversed-phase high performance liquid chromatography. Under the conditions used, the radioactivity was found in (24E)-3 alpha,7 alpha-dihydroxy-5 beta-cholest-24-enoic acid (31%) and (24R,25S)-3 alpha,7 alpha,24-trihydroxy-5 beta-cholestanoic acid (7%) along with the starting material (62%). Neither the 24Z isomer of the alpha,beta-unsaturated bile acid nor the other three isomers of the beta-hydroxy bile acid were detected. The findings support the proposed pathway for the side chain cleavage in chenodeoxycholic acid biosynthesis, which is thought to be identical to that of cholic acid biosynthesis.
Une
M
M
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
Inoue
A
A
Kurosawa
T
T
Tohma
M
M
Hoshita
T
T
D000818:Animals; D002250:Carbon Radioisotopes; D002635:Chenodeoxycholic Acid / Q000096:biosynthesis*; D002777:Cholestanols / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
C000986:3,7-dihydroxycholestan-26-oic acid; D002250:Carbon Radioisotopes; D002777:Cholestanols; D002635:Chenodeoxycholic Acid; C059108:3,7,12-trihydroxycholest-24-enoic acid; D002784:Cholesterol