title: Kinetic characteristics of rat liver peroxisomal nafenopin-CoA ligase.
abstract: In this study we have demonstrated that rat hepatic peroxisomes catalyse the formation of nafenopin-CoA. The process is mediated by apparent high affinity (Km 6.7 microM), low capacity (Vmax 0.31 nmol/mg/min) and low affinity, high capacity isoforms. Palmitic acid (Ki 1.1 microM), R(-) ibuprofen (Ki 7.9 microM), ciprofibrate (Ki 60.2 microM) and clofibric acid (Ki 86.8 microM) competitively inhibited nafenopin-CoA formation catalysed by the apparent high affinity isoform. An antibody raised against the microsomal palmitoyl-CoA ligase inhibited the equivalent peroxisomal enzyme significantly (P < 0.001) but did not inhibit peroxisomal nafenopin-CoA ligase activity. These data suggest that nafenopin-CoA formation is catalysed by a peroxisomal CoA ligase which differs from the peroxisomal long chain fatty acid-CoA ligase in relation to its xenobiotic/antibody inhibitor profile and kinetic characteristics.
authors.affiliation: Department of Clinical Pharmacology, Flinders University of South Australia, Bedford Park.
authors.forename: B J
authors.initials: BJ
authors.lastname: Roberts
authors.forename: J K
authors.initials: JK
authors.lastname: MacLeod
authors.forename: I
authors.initials: I
authors.lastname: Singh
authors.forename: K M
authors.initials: KM
authors.lastname: Knights
mesh_terms: D000818:Animals; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058607:Fibric Acids; D007052:Ibuprofen / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008830:Microbodies / Q000201:enzymology*; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D058607:Fibric Acids; D010169:Palmitic Acids; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D019308:Palmitic Acid; D002995:Clofibric Acid; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; C019304:ciprofibrate; D007052:Ibuprofen