The reactions catalyzed by the inducible bifunctional enzyme of rat liver peroxisomes cannot lead to the formation of bile acids.
The ability of the bifunctional 2-enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase from rat liver peroxisomes to metabolize (24E)-3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholest-24-enoyl-CoA, a presumed intermediate during the beta-oxidative degradation of the steroid side chain in the formation of cholic acid, was investigated. The bifunctional enzyme efficiently hydrated the above compound specifically to (24S,25S)-3alpha, 7alpha, 12alpha, 24-tetrahydroxy-5beta-cholestanoyl-CoA, but the dehydrogenase component of the enzyme was virtually inactive toward this product. In contrast, the bifunctional enzyme efficiently catalyzed the dehydrogenation of the (24S,25R) diastereomer of the above hydroxy intermediate to two products whose uv absorbance and chemical properties were consistent with those of alpha-methyl-beta-ketoacyl-CoAs. These results suggest that the bifunctional enzyme is not sufficient for the formation of a 24-keto intermediate in bile acid biosynthesis.
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Department of Chemistry, Southwest Missouri State University, Springfield, 65804, USA.
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D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism*; D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002384:Catalysis; D004746:Enoyl-CoA Hydratase / Q000378:metabolism*; D007535:Isomerases / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008830:Microbodies / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D063994:Peroxisomal Bifunctional Enzyme; D051381:Rats; D013237:Stereoisomerism
D001647:Bile Acids and Salts; D009097:Multienzyme Complexes; D009243:NAD; D015094:3-Hydroxyacyl CoA Dehydrogenases; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases