Conclusive evidence that very-long-chain fatty acids are oxidized exclusively in peroxisomes in human skin fibroblasts.
We have investigated the contribution of peroxisomes and mitochondria to the beta-oxidation of palmitate (C16:0) and cerotate (C26:0) in intact human skin fibroblasts. The oxidation of both fatty acids was found to be inhibited by rotenone plus antimycin and cyanide, respectively, although to a different extent. When 2-[5-(4-chlorophenyl)pentyl]-oxirane-2-carboxylate (POCA) was used to specifically block carnitine palmitoyltransferase I, it was found that palmitate beta-oxidation was inhibited almost completely whereas cerotate beta-oxidation was not affected. Since carnitine palmitoyltransferase is essential for the oxidation of fatty acids in mitochondria this result provides conclusive evidence that oxidation of very-long-chain fatty acids is initiated in peroxisomes and not in mitochondria.
Jakobs
B S
BS
Dept. of Clinical Biochemistry, University Hospital Amsterdam, The Netherlands.
Wanders
R J
RJ
D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D004852:Epoxy Compounds / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007700:Kinetics; D008830:Microbodies / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism*; D011190:Potassium Cyanide / Q000494:pharmacology; D012402:Rotenone / Q000494:pharmacology; D012867:Skin / Q000378:metabolism*
D004852:Epoxy Compounds; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D010169:Palmitic Acids; D012402:Rotenone; C032456:antimycin; D019308:Palmitic Acid; D000968:Antimycin A; C035111:B 807-27; C017364:hexacosanoic acid; D011190:Potassium Cyanide