Author:

Keywords:

Acyl Coenzyme A, Adult, Animals, Bile Acids and Salts, Chromatography, Chromatography, Gel, Chromatography, Ion Exchange, Durapatite, Electrophoresis, Polyacrylamide Gel, Humans, Hydroxyapatites, Kidney, Kinetics, Liver, Microbodies, Molecular Weight, Oxidoreductases, Rats, Research Support, Non-U.S. Gov't, Subcellular Fractions, Substrate Specificity, Zellweger Syndrome, Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, RAT-LIVER, BETA-OXIDATION, ZELLWEGER SYNDROME, DEFICIENCY, PROTEINS, DISORDER, ENZYMES, POLYACRYLAMIDE, GELS, 03 Chemical Sciences, 06 Biological Sciences, 11 Medical and Health Sciences, 31 Biological sciences, 32 Biomedical and clinical sciences, 34 Chemical sciences

Abstract:

Rat liver peroxisomes contain three acyl-CoA oxidases: palmitoyl-CoA oxidase, which oxidizes the CoA esters of straight chain fatty acids and prostaglandins; pristanoyl-CoA oxidase, which oxidizes the CoA esters of 2-methyl-branched fatty acids (e.g. pristanic acid); and trihydroxycoprostanoyl-CoA oxidase, which oxidizes the CoA esters of the bile acid intermediates di- and trihydroxycoprostanic acids (Van Veldhoven, P. P., Vanhove, G., Asselberghs, S., Eyssen, H. J., and Mannaerts, G. P. (1992) J. Biol. Chem. 267, 20065-20074). In the present report we demonstrate that human liver peroxisomes contain only two acyl-CoA oxidases: palmitoyl-CoA oxidase, which oxidizes the CoA esters of straight chain fatty acids and prostaglandins, and a novel branched chain acyl-CoA oxidase, which oxidizes the CoA esters of 2-methyl-branched fatty acids as well as those of the bile acid intermediates (which also possess a 2-methyl substitution in their side chains). The branched chain acyl-CoA oxidase was purified to near homogeneity by means of column chromatography. It appeared to be a 70-kDa monomeric protein that did not cross-react with antisera raised against rat palmitoyl-CoA oxidase and pristanoyl-CoA oxidase. No indication was found for the presence of a separate trihydroxycoprostanoyl-CoA oxidase in human liver. The branched chain acyl-CoA oxidase was present also in human kidney, suggesting that it is expressed in other extrahepatic tissues as well. Our results explain a number of clinical-chemical observations made in certain cases of peroxisomal beta-oxidation disorders.