Studies on the transport of acetyl groups from peroxisomes to mitochondriain isolated liver cells oxidizing the polyunsaturated fatty acid 22 : 4n-6

The oxidation of the fatty acid [I-C-14]22:4n-6 was studied in isolated hep atocytes. Labeled acetate was the main acid soluble product identified by H PLC after short incubation periods. At low substrate concentrations and lon ger incubations [C-14]acetate was gradually replaced by labeled beta -hydro xybutyrate, acetoacetate and oxaloacetate/malate. Preincubation with 2-tetr adecylglycidic acid (TDGA), an inhibitor of mitochondrial fatty acid oxidat ion, did not reduce the oxidation but acetate was the only product recovere d. TDGA also strongly inhibited the metabolism of added [I-C-14]acetate to mitochondrial oxidation products. During the preparation procedure of hepat ocytes the cellular L-carnitine concentration was decreased but it was rest ored after preincubation with L-carnitine. With low [I-C-14]22:4n-6, concen trating a low level of [C-14]acetate and high levels of labeled mitochondri al oxidation products were recovered after preincubation with L-carnitine. A small amount of [C-14]acetylcarnitine was also detected under this incuba tion condition. The results suggest that a significant part of labeled acet yl groups from the peroxisomal oxidation of [1-C-14]22:4n-6 is transported to the mitochondria as free acetate. Moreover, the results also suggest tha t L-carnitine at physiological concentrations may facilitate the transport of part of the acetyl groups from peroxisomes to mitochondria as acetylcarn itine. However, the possibility that an increased cellular L-carnitine conc entration may stimulate oxidation of [1-C-14]22:4n-6 in mitochondria could not be excluded. (C) 2001 Elsevier Science B.V. All rights reserved.