TY - JOUR
T1 - ω‐Hydroxylation of Steroid Side‐Chain in Biosynthesis of Bile Acids
AU - BjÖRKHEM, Ingemar
AU - Gustafsson, Jan-Ake
PY - 1973/1/1
Y1 - 1973/1/1
N2 - ;. Hydroxylation (26 hydroxylation) of various C27 steroids by the microsomal and mitochondrial fraction was studied. Assay conditions for the microsomal 26 hydroxylation were determined with 5β cholestane 3α,7α diol as substrate. NADPH was the required cofactor. NADH stimulated the hydroxylation at suboptimal concentrations of NADPH. The hydroxylation was inhibited markedly by carbon monoxide Treatment with phenobarbital inhibited the reaction whereas starvation or biliary drainage had no significant effect. The rates of microsomal 26 hydroxylation of different C27 steroids expressed in nmol/mg protein per 20 min were cholesterol, <0.1; 5 cholestene 3β,7α diol, <0.1; 7α hydroxy 4 cholesten 3 one, 0.3; 7α,12α dihydroxy 4 cholesten 3 one, 0.9; 5β cholestane 3α,7α diol, 1.8; 5β cholestane 3α,7α,12α triol, 2.7. Assay conditions for the mitochondrial 26 hydroxylation were determined with cholesterol and 5β cholestane 3α,7α diol as substrates. The rate of reaction was faster with an NADPH generating system than with NADPH. The reaction was inhibited markedly with carbon monoxide. Biliary drainage inhibited the reaction whereas starvation or treatment with phenobarbital had no significant effect. The rates of mitochondrial 26 hydroxylation of different C27 steroids expressed in nmol/mg protein per 20 min were: cholesterol, 0.3; 5 cholestene 3β,7α diol, 0.9; 7α hydroxy 4 cholesten 3 one, 1.7; 7α,12α dihydroxy 4 cholesten 3 one, 0.9; 5β cholestane 3α,7α diol, 0.9; 5β cholestane 3α,7α,12α triol, 2.0. The results are consistent with previously postulated pathways concerning biosynthesis of cholic acid and chenodeoxycholic acid in which 5β cholestane 3α,7α,12α triol and 5β cholestane 3α,7α diol, respectively are the main substrates for the 26 hydroxylase. The possibility is discussed that pathways involving intermediary formation of 7α,26 dihydroxy 4 cholesten 3 one and 7α,12α,26 trihydroxy 4 cholesten 3 one also are of importance in the biosynthesis of bile acids.
AB - ;. Hydroxylation (26 hydroxylation) of various C27 steroids by the microsomal and mitochondrial fraction was studied. Assay conditions for the microsomal 26 hydroxylation were determined with 5β cholestane 3α,7α diol as substrate. NADPH was the required cofactor. NADH stimulated the hydroxylation at suboptimal concentrations of NADPH. The hydroxylation was inhibited markedly by carbon monoxide Treatment with phenobarbital inhibited the reaction whereas starvation or biliary drainage had no significant effect. The rates of microsomal 26 hydroxylation of different C27 steroids expressed in nmol/mg protein per 20 min were cholesterol, <0.1; 5 cholestene 3β,7α diol, <0.1; 7α hydroxy 4 cholesten 3 one, 0.3; 7α,12α dihydroxy 4 cholesten 3 one, 0.9; 5β cholestane 3α,7α diol, 1.8; 5β cholestane 3α,7α,12α triol, 2.7. Assay conditions for the mitochondrial 26 hydroxylation were determined with cholesterol and 5β cholestane 3α,7α diol as substrates. The rate of reaction was faster with an NADPH generating system than with NADPH. The reaction was inhibited markedly with carbon monoxide. Biliary drainage inhibited the reaction whereas starvation or treatment with phenobarbital had no significant effect. The rates of mitochondrial 26 hydroxylation of different C27 steroids expressed in nmol/mg protein per 20 min were: cholesterol, 0.3; 5 cholestene 3β,7α diol, 0.9; 7α hydroxy 4 cholesten 3 one, 1.7; 7α,12α dihydroxy 4 cholesten 3 one, 0.9; 5β cholestane 3α,7α diol, 0.9; 5β cholestane 3α,7α,12α triol, 2.0. The results are consistent with previously postulated pathways concerning biosynthesis of cholic acid and chenodeoxycholic acid in which 5β cholestane 3α,7α,12α triol and 5β cholestane 3α,7α diol, respectively are the main substrates for the 26 hydroxylase. The possibility is discussed that pathways involving intermediary formation of 7α,26 dihydroxy 4 cholesten 3 one and 7α,12α,26 trihydroxy 4 cholesten 3 one also are of importance in the biosynthesis of bile acids.
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U2 - 10.1111/j.1432-1033.1973.tb02902.x
DO - 10.1111/j.1432-1033.1973.tb02902.x
M3 - Article
C2 - 4147366
AN - SCOPUS:0015693755
VL - 36
SP - 201
EP - 212
JO - European Journal of Biochemistry
JF - European Journal of Biochemistry
SN - 0014-2956
IS - 1
ER -