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

The oxidation of the fatty acid [1-14C]22:4n–6 was studied in isolated hepatocytes. Labeled acetate was the main acid soluble product identified by HPLC after short incubation periods. At low substrate concentrations and longer incubations [14C]acetate was gradually replaced by labeled β-hydroxybutyrate, acetoacetate and oxaloacetate/malate. Preincubation with 2-tetradecylglycidic acid (TDGA), an inhibitor of mitochondrial fatty acid oxidation, did not reduce the oxidation but acetate was the only product recovered. TDGA also strongly inhibited the metabolism of added [1-14C]acetate to mitochondrial oxidation products. During the preparation procedure of hepatocytes the cellular -carnitine concentration was decreased but it was restored after preincubation with -carnitine. With low [1-14C]22:4n–6, concentrating a low level of [14C]acetate and high levels of labeled mitochondrial oxidation products were recovered after preincubation with -carnitine. A small amount of [14C]acetylcarnitine was also detected under this incubation condition. The results suggest that a significant part of labeled acetyl groups from the peroxisomal oxidation of [1-14C]22:4n–6 is transported to the mitochondria as free acetate. Moreover, the results also suggest that -carnitine at physiological concentrations may facilitate the transport of part of the acetyl groups from peroxisomes to mitochondria as acetylcarnitine. However, the possibility that an increased cellular -carnitine concentration may stimulate oxidation of [1-14C]22:4n–6 in mitochondria could not be excluded.