Study on Stereospecificity of Enzyme Reaction Related to Peroxisomal Bile Acid Synthesis in Rat Liver

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We examined stereoselectivities of enzymes related to bile acid formation in hepatic peroxisomes using two stereoisomers of 3α, 7α, 12α-trihydroxy-5β-cholestanoic acid (THCA) and its coenzyme A (CoA) derivatives. The activity of acyl-CoA synthetase for 25S-THCA was 1.4-times higher than that for 25R-THCA. The difference was also observed after clofibrate-treatment. This activity was located in microsomes, differing from palmitoyl-CoA synthetase located in mitochondria, peroxisomes and microsomes. There was no stereoselectivity in the reaction of peroxisomal fatty acyl-CoA oxidase for THCA isomers, and the activity was one tenth of that for acyl-CoA synthetase. Considering the overall raction of peroxisomal bile acid formation, the stereoselective difference observed in THCA-CoA synthesis should be denied. Thus, the previous finding that the overall formation of bile acid from THCA was not stereoselective was further confirmed. Furthermore, the activity for THCA oxidation was not induced by clofibric acid, suggesting that there would be different isozymes of peroxisomal acyl-CoA oxidase against THCA-CoA and palmitoyl-CoA.
1992-02-25