Peroxisomal fatty acid oxidation and inhibitors of the mitochondrial carnitine palmitoyltransferase I in isolated rat hepatocytes.
Fatty acid oxidation was studied in the presence of inhibitors of carnitine palmitoyltransferase I (CPT I), in normal and in peroxisome-proliferated rat hepatocytes. The oxidation decreased in mitochondria, as expected, but in peroxisomes it increased. These two effects were seen, in variable proportions, with (+)-decanoylcarnitine, 2-tetradecylglycidic acid (TDGA) and etomoxir. The decrease in mitochondrial oxidation (ketogenesis) affected saturated fatty acids with 12 or more carbon atoms, whereas the increase in peroxisomal oxidation (H2O2 production) affected saturated fatty acids with 8 or more carbon atoms. The peroxisomal increase was sensitive to chlorpromazine, a peroxisomal inhibitor. To study possible mechanisms, palmitoyl-, octanoyl- and acetyl-carnitine acyltransferase activities were measured, in homogenates and in subcellular fractions from control and TDGA-treated cells. The palmitoylcarnitine acyltransferase was inhibited, as expected, but the octanoyltransferase activity also decreased. The CoA derivative of TDGA was synthesized and tentatively identified as being responsible for inhibition of the octanoylcarnitine acyltransferase. These results show that inhibitors of the mitochondrial CPT I may also inhibit the peroxisomal octanoyl transferase; they also support the hypothesis that the octanoyltransferase has the capacity to control or regulate peroxisomal fatty acid oxidation.
Skorin
C
C
Departamento de Biología Celular y Molecular, Universidad Católica de Chile.
Necochea
C
C
Johow
V
V
Soto
U
U
Grau
A M
AM
Bremer
J
J
Leighton
F
F
D000818:Animals; D002333:Carnitine Acyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002332:Carnitine O-Acetyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007659:Ketones / Q000378:metabolism; D008297:Male; D008830:Microbodies / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000201:enzymology*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004852:Epoxy Compounds; D005227:Fatty Acids; D007659:Ketones; D010168:Palmitates; D006861:Hydrogen Peroxide; D002333:Carnitine Acyltransferases; C030162:carnitine octanoyltransferase; D002334:Carnitine O-Palmitoyltransferase; D002332:Carnitine O-Acetyltransferase; C021756:2-tetradecylglycidic acid; D002746:Chlorpromazine