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.
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.
Dahlbäck
H
H
Department of Pharmaceutical Biochemistry, University of Uppsala, Sweden.
Danielsson
H
H
Gustafsson
M
M
Sjövall
J
J
Wikvall
K
K
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D002777:Cholestanols / Q000378:metabolism*; D004221:Disulfiram / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000201:enzymology*; D011720:Pyrazoles / Q000494:pharmacology; D011817:Rabbits; D013010:Sonication
D002777:Cholestanols; D011720:Pyrazoles; C056061:4-heptylpyrazole; C022069:3,7,12-trihydroxycholestan-26-oic acid; C020262:cholestane-3,7,12,26-tetrol; D000429:Alcohol Oxidoreductases; D004221:Disulfiram