Conversion of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 26-tetrol into 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid by rabbit liver mitochondria |
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| Authors: | H Dahlb?ck H Danielsson M Gustafsson J Sj?vall K Wikvall |
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| Institution: | Department of Pharmaceutical Biochemistry, University of Uppsala, Sweden. |
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| Abstract: | Rabbit liver mitochondria in the presence of NAD+ were found to catalyze the conversion of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 26-tetrol into 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid. The peroxisomal fraction did not catalyze the reaction. Sonication of the mitochondria or dialysis overnight against a hypotonic buffer increased the rate of oxidation twofold. Most of the enzyme activity was recovered in the supernatant fraction after centrifugation at 100,000xg of sonicated mitochondria. 4-Heptylpyrazole, an inhibitor of cytosolic ethanol dehydrogenase, inhibited the mitochondrial formation of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid by 70%. Disulfiram, an inhibitor of cytosolic acetaldehyde dehydrogenase, did not inhibit the reaction. The role of the mitochondrial dehydrogenase system in bile acid biosynthesis is discussed. |
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