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 i ncubated with rat liver homogenate (800 x g supernatant and light mito chondrial fraction) to study substrate specificity in the side-chain c leavage reaction (beta-oxidation) of bile acid biosynthesis. The C-27- intermediates (5 beta-cholest-24-en-26-oic acids and 24-hydroxy-5 beta -cholestan-26-oic acids) in beta-oxidation and the corresponding, C-24 -bile acids were quantitatively determined by capillary gas chromatogr aphy. Monohydroxy-5 beta-cholestan-26-oic acid was not converted into C-24-bile acid. Di- and trihydroxy-5 beta-cholestan-26-oic acids were effectively transformed into the C-27-intermediates and C-24-bile acid s. Tetrahydroxy-5 beta-cholestan-26-oic acids were also converted into C-27-intermediates and corresponding C-24-bile acids. The intermediat es 24-hydroxy-5 beta-cholestan-26-oic acids could not be detected in t he products by incubation with the light mitochondrial fraction. The t otal specific activity of protein in the light mitochondrial fraction of the production of C-27-intermediates and C-24-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. (C) 1997 by Elsevier Science Inc.