Molecular Cloning and Expression of Human Carnitine Octanoyltransferase: Evidence for Its Role in the Peroxisomal β-Oxidation of Branched-Chain Fatty Acids

• Published in: Biochemical and biophysical research communications Vol. 263; no. 1; pp. 213 - 218
• Main Authors: Ferdinandusse, Sacha, Mulders, Joyce, IJlst, Lodewijk, Denis, Simone, Dacremont, Georges, Waterham, Hans R., Wanders, Ronald J.A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.09.1999
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Carnitine Acyltransferases - genetics; Carnitine Acyltransferases - metabolism; Cattle; Cloning, Molecular; DNA Primers - genetics; DNA, Complementary - genetics; Fatty Acids - metabolism; Gene Expression; Humans; In Vitro Techniques; Microbodies - metabolism; Molecular Sequence Data; Oxidation-Reduction; Rats; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Sequence Homology, Amino Acid; Species Specificity
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.1340

To study the putative role of human carnitine octanoyltransferase (COT) in the β-oxidation of branched-chain fatty acids, we identified and cloned the cDNA encoding human COT and expressed it in the yeast Saccharomyces cerevisiae. Enzyme activity measurements showed that COT efficiently converts one of the end products of the peroxisomal β-oxidation of pristanic acid, 4,8-dimethylnonanoyl-CoA, to its corresponding carnitine ester. Production of the carnitine ester of this branched/medium-chain acyl-CoA within the peroxisome is required for its transport to the mitochondrion where further β-oxidation occurs. In contrast, 4,8-dimethylnonanoyl-CoA is not a substrate for carnitine acetyltransferase, another acyltransferase localized in peroxisomes, which catalyzes the formation of carnitine esters of the other products of pristanic acid β-oxidation, namely acetyl-CoA and propionyl-CoA. Our results shed new light on the function of COT in fatty acid metabolism and point to a crucial role of COT in the β-oxidation of branched-chain fatty acids.