title: Molecular cloning and expression of human carnitine octanoyltransferase: evidence for its role in the peroxisomal beta-oxidation of branched-chain fatty acids.
abstract: To study the putative role of human carnitine octanoyltransferase (COT) in the beta-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 beta-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 beta-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 beta-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 beta-oxidation of branched-chain fatty acids.
authors.affiliation: Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Academic Medical Center, Amsterdam, 1100 DE, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Ferdinandusse
authors.forename: J
authors.initials: J
authors.lastname: Mulders
authors.forename: L
authors.initials: L
authors.lastname: IJlst
authors.forename: S
authors.initials: S
authors.lastname: Denis
authors.forename: G
authors.initials: G
authors.lastname: Dacremont
authors.forename: H R
authors.initials: HR
authors.lastname: Waterham
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002333:Carnitine Acyltransferases / Q000235:genetics* / Q000378:metabolism*; D002417:Cattle; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D008830:Microbodies / Q000378:metabolism; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D005227:Fatty Acids; D011994:Recombinant Proteins; C002844:pristanic acid; D002333:Carnitine Acyltransferases; C030162:carnitine octanoyltransferase