TY - JOUR
T1 - Bioconversion of 3β-hydroxy-5-cholenoic acid into chenodeoxycholic acid by rat brain enzyme systems
AU - Mano, Nariyasu
AU - Sato, Yoshiaki
AU - Nagata, Masanori
AU - Goto, Takaaki
AU - Goto, Junichi
PY - 2004/9
Y1 - 2004/9
N2 - 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 24S-hydroxycholesterol, which plays an important role in cholesterol homeostasis in the body.
AB - 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 24S-hydroxycholesterol, which plays an important role in cholesterol homeostasis in the body.
KW - Biosynthesis
KW - Brain bile acid
KW - Cholesterol homeostasis
KW - Stable isotope dilution
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U2 - 10.1194/jlr.M400157-JLR200
DO - 10.1194/jlr.M400157-JLR200
M3 - Article
C2 - 15175361
AN - SCOPUS:4644303733
VL - 45
SP - 1741
EP - 1748
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 9
ER -