Association of the liver peroxisomal fatty acyl-CoA beta-oxidation system with the synthesis of bile acids.
The association of liver peroxisomal fatty acyl-CoA beta-oxidizing system (FAOS) with the synthesis of bile acids was investigated. When rats were given clofibrate, a peroxisome proliferator and stimulator of peroxisomal FAOS, the biosynthesis of bile acids was significantly increased. Di(2-ethylhexyl)phthalate, another peroxisome proliferator, also increased the biosynthesis of bile acids. On the other hand, administration of orotate, an inhibitor of mitochondrial FAOS activity, did not affect the biosynthesis. It is known that fatty acyl-CoA oxidase [EC 1.3.99.3] in peroxisomal FAOS conjugates with catalase [EC 1.11.1.6]. When the catalase activity of liver peroxisomes was irreversibly inhibited by administration of 3-amino-1,2,4-triazole (amino-triazole), the biosynthesis of bile acids was suppressed to about one-third, and the serum cholesterol level was increased. However, the bile acid components of the bile obtained from aminotriazole-treated rats were not essentially different from those of control rats, and no accumulation of intermediates of bile acid synthesis was found in this experiment. Peroxisomal FAOS activity of the liver from amino-triazole-treated rats was considerably lower than that of control liver. The above results indicate that liver peroxisomes play a role in the biosynthesis of bile acids in vivo.
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002784:Cholesterol / Q000097:blood; D002994:Clofibrate / Q000494:pharmacology; D004051:Diethylhexyl Phthalate / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D000214:Acyl Coenzyme A; D001647:Bile Acids and Salts; D000960:Hypolipidemic Agents; D002784:Cholesterol; D004051:Diethylhexyl Phthalate; D002994:Clofibrate; D000640:Amitrole