Inhibition of peroxisomal fatty acyl-CoA oxidase by antimycin A.
Peroxisomal fatty acyl-CoA oxidase was inhibited by micromolar concentrations of antimycin A, an inhibitor of mitochondrial respiration. The inhibition was observed with all three substrates tested, i.e. palmitoyl-CoA, trihydroxycoprostanoyl-CoA and hexadecanedioyl-CoA. The peroxisomal D-amino acid oxidase was also inhibited by antimycin, but the peroxisomal L-alpha-hydroxyacid oxidase and uric acid oxidase and the mitochondrial monoamine oxidase were not. The degree of inhibition of acyl-CoA oxidase by antimycin was strongly dependent on the amount of cellular protein present in the assay mixture: at a fixed antimycin concentration, the inhibition was gradually lost with increasing protein concentrations. At a fixed cellular protein concentration in the assay mixtures, the mitochondrial oxidation of glutamate or palmitoylcarnitine was inhibited at antimycin concentrations that were much lower than those required for the inhibition of fatty acyl-CoA oxidase. Our results, nevertheless, demonstrate that antimycin A must be used with caution, when it is added to homogenates or subcellular fractions in order to distinguish between mitochondrial and peroxisomal fatty acid oxidation.
Vamecq
J
J
Université Catholique de Louvain, Brussels, Belgium.
Schepers
L
L
Parmentier
G
G
Mannaerts
G P
GP
D042962:Acyl-CoA Oxidase; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology*; D002499:Centrifugation, Density Gradient; D002793:Cholic Acids / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008830:Microbodies / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012402:Rotenone / Q000494:pharmacology; D013347:Subcellular Fractions / Q000201:enzymology
D002793:Cholic Acids; D011506:Proteins; D012402:Rotenone; D000968:Antimycin A; C003681:3,7,12-trihydroxycoprostanic acid; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase