Effect of the hydroxyl group on the oxidative cleavage (beta-oxidation) of steroidal side chain for bile acid biosynthesis in rat liver homogenate.
Mono-, di-, tri-, and tetrahydroxy-5 beta-cholestan-26-oic acids were incubated with rat liver homogenate (800 x g supernatant and light mitochondrial fraction) to study substrate specificity in the side-chain cleavage reaction (beta-oxidation) of bile acid biosynthesis. The C27-intermediates (5 beta-cholest-24-en-26-oic acids and 24-hydroxy-5 beta-cholestan-26-oic acids) in beta-oxidation and the corresponding C24-bile acids were quantitatively determined by capillary gas chromatography. Monohydroxy-5 beta-cholestan-26-oic acid was not converted into C24-bile acid. Di- and trihydroxy-5 beta-cholestan-26-oic acids were effectively transformed into the C27-intermediates and C24-bile acids. Tetrahydroxy-5 beta-cholestan-26-oic acids were also converted into C27-intermediates and corresponding C24-bile acids. The intermediate 24-hydroxy-5 beta-cholestan-26-oic acids could not be detected in the products by incubation with the light mitochondrial fraction. The total specific activity of protein in the light mitochondrial fraction for the production of C27-intermediates and C24-bile acids was higher than that of 800 x g supernatant solution. The effects of the number and the position of hydroxyl groups on the side-chain degradation are discussed.
Kurosawa
T
T
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan.
Sato
M
M
Kikuchi
F
F
Watanabe
T
T
Suga
T
T
Tohma
M
M
D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002849:Chromatography, Gas; D017665:Hydroxyl Radical / Q000378:metabolism*; D006900:Hydroxylation; D008099:Liver / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011921:Rats, Inbred WKY; D013379:Substrate Specificity
D001647:Bile Acids and Salts; D017665:Hydroxyl Radical