出版社：American Society for Biochemistry and Molecular Biology
摘要：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 3β-hydroxy-5-cholenoic acid into CDCA in rat brain tissue. To distinguish marked compounds from endogenous related compounds, 18O-labeled 3β-hydroxy-5-cholenoic acid, 3β,7α-dihydroxy-5-cholenoic acid, and 7α-hydroxy-3-oxo-4-cholenoic acid were synthesized as substrates for in vitro incubation studies. The results clearly suggest that 3β-hydroxy-5-cholenoic acid was converted to 3β,7α-dihydroxy-5-cholenoic acid by microsomal enzymes. The 7α-hydroxy-3-oxo-4-cholenoic acid was produced from 3β,7α-dihydroxy-5-cholenoic acid by the action of microsomal enzymes, and Δ4-3-oxo acid was converted to CDCA by cytosolic enzymes. These findings indicate the presence of an enzymatic activity that converts 3β-hydroxy-5-cholenoic acid into CDCA in rat brain tissue. Furthermore, this synthetic pathway for CDCA may relate to the function of 24 S -hydroxycholesterol, which plays an important role in cholesterol homeostasis in the body.
