title: Studies on the effect of fenoprofen on the activation and oxidation of long chain and very long chain fatty acids in hepatocytes and subcellular fractions from rat liver.
abstract: We studied the effect of fenoprofen on the activation of palmitic acid (C16:0), lignoceric acid (C24:0) and cerotic acid (C26:0) in microsomal and peroxisomal fractions from rat liver. Fenoprofen was found to inhibit the formation of palmitoyl-CoA in both microsomal and peroxisomal fractions whereas the formation of lignoceroyl-CoA and cerotoyl-CoA was not inhibited at all. In freshly isolated rat hepatocytes palmitic acid beta-oxidation was progressively inhibited at increasing concentrations of fenoprofen, most probably due to its inhibitory effect on palmitoyl-CoA synthetase activity. On the other hand, fenoprofen was also found to inhibit the beta-oxidation of lignoceric acid and cerotic acid in rat hepatocytes. It is shown that the acyl-CoA oxidase activity with lignoceroyl-CoA as substrate was inhibited by fenoprofen whereas the palmitoyl-CoA and pristanoyl-CoA oxidase activities were not inhibited by fenoprofen. This finding provides an explanation for the inhibitory effect of fenoprofen on lignocerate and cerotate beta-oxidation in hepatocytes.
authors.affiliation: Department of Clinical Biochemistry, University of Amsterdam, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Lageweg
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism*; D005279:Fenoprofen / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008830:Microbodies / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D010169:Palmitic Acids; D019308:Palmitic Acid; D010088:Oxidoreductases; C082494:lignoceroyl-CoA oxidase; D005279:Fenoprofen; C010210:lignoceric acid