title: Bioconversion of 3beta-hydroxy-5-cholenoic acid into chenodeoxycholic acid by rat brain enzyme systems.
abstract: We have previously demonstrated that the rat brain contains three unconjugated bile acids, and chenodeoxycholic acid (CDCA) is the most abundantly present in a tight protein binding form. The ratio of CDCA to the other acids in rat brain tissue was significantly higher than the ratio in the peripheral blood, indicating a contribution from either a specific uptake mechanism or a biosynthetic pathway for CDCA in rat brain. In this study, we have demonstrated the existence of an enzymatic activity that converts 3beta-hydroxy-5-cholenoic acid into CDCA in rat brain tissue. To distinguish marked compounds from endogenous related compounds, 18O-labeled 3beta-hydroxy-5-cholenoic acid, 3beta,7alpha-dihydroxy-5-cholenoic acid, and 7alpha-hydroxy-3-oxo-4-cholenoic acid were synthesized as substrates for in vitro incubation studies. The results clearly suggest that 3beta-hydroxy-5-cholenoic acid was converted to 3beta,7alpha-dihydroxy-5-cholenoic acid by microsomal enzymes. The 7alpha-hydroxy-3-oxo-4-cholenoic acid was produced from 3beta,7alpha-dihydroxy-5-cholenoic acid by the action of microsomal enzymes, and Delta4-3-oxo acid was converted to CDCA by cytosolic enzymes. These findings indicate the presence of an enzymatic activity that converts 3beta-hydroxy-5-cholenoic acid into CDCA in rat brain tissue. Furthermore, this synthetic pathway for CDCA may relate to the function of 24S-hydroxycholesterol, which plays an important role in cholesterol homeostasis in the body.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Aoba, Sendai 980-8578, Japan.
authors.forename: Nariyasu
authors.initials: N
authors.lastname: Mano
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sato
authors.forename: Masanori
authors.initials: M
authors.lastname: Nagata
authors.forename: Takaaki
authors.initials: T
authors.lastname: Goto
authors.forename: Junichi
authors.initials: J
authors.lastname: Goto
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D002635:Chenodeoxycholic Acid / Q000096:biosynthesis*; D002789:Cholesterol Oxidase / Q000378:metabolism*; D002793:Cholic Acids / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008968:Molecular Conformation; D009249:NADP / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D002793:Cholic Acids; D002635:Chenodeoxycholic Acid; C014596:3 beta-hydroxy-delta 5-cholenic acid; D009249:NADP; D002789:Cholesterol Oxidase