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

• Published in: Biochimica et biophysica acta 2001-10, Vol.1533 (3), p.255-265
• Main Authors: Tran, T N, Christophersen, B O
• Format: Article
• Language: English
• Subjects: Acetates - analysis; Acetates - metabolism; Acetyl Coenzyme A - analysis; Acetyl Coenzyme A - metabolism; Animals; Biological Transport; Carbon Dioxide - analysis; Carbon Radioisotopes; Carnitine - pharmacology; Cells, Cultured; Epoxy Compounds - pharmacology; Fatty Acids - pharmacology; Fatty Acids, Unsaturated - metabolism; Liver - metabolism; Male; Mitochondria, Liver - metabolism; Oxidation-Reduction; Palmitic Acid - metabolism; Peroxisomes - metabolism; Rats; Rats, Wistar
• ISSN: 0006-3002; 1388-1981
• DOI: 10.1016/s1388-1981(01)00159-7

The oxidation of the fatty acid [1-(14)C]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 [(14)C]acetate was gradually replaced by labeled beta-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-(14)C]acetate to mitochondrial oxidation products. During the preparation procedure of hepatocytes the cellular L-carnitine concentration was decreased but it was restored after preincubation with L-carnitine. With low [1-(14)C]22:4n-6, concentrating a low level of [(14)C]acetate and high levels of labeled mitochondrial oxidation products were recovered after preincubation with L-carnitine. A small amount of [(14)C]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-(14)C]22:4n-6 is transported to the mitochondria as free acetate. Moreover, the results also suggest that L-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 L-carnitine concentration may stimulate oxidation of [1-(14)C]22:4n-6 in mitochondria could not be excluded.