STUDIES ON PHYTANIC ACID ALPHA-OXIDATION IN RAT-LIVER AND CULTURED HUMAN SKIN FIBROBLASTS

We have studied the a-oxidation of phytanic acid in rat liver and huma n skin fibroblasts in order to try to resolve the controversial issue of the subcellular site of alpha-oxidation of phytanic acid. The resul ts show that isolated mitochondria are able to alpha-oxidize phytanic acid whereas isolated peroxisomes show no phytanic acid alpha-oxidatio n activity. Intact hepatocytes were found to alpha-oxidize phytanic ac id at a rate which is more than 20-fold higher than the activity found in postnuclear supernatant fractions incubated under optimal conditio ns. The alpha-oxidation of phytanic acid was found to be sensitive to inhibitors of the respiratory chain and an uncoupler of oxidative phos phorylation. Furthermore, the alpha-oxidation of phytanic acid was fou nd to be deficient in cultured human skin fibroblasts with an inherite d deficiency of cytochrome c oxidase and in fibroblasts with a deficie ncy of functional peroxisomes. We conclude that mitochondria are indis pensable for phytanic acid alpha-oxidation. Furthermore, we propose th at one (or more) of the partial reactions in phytanic acid alpha-oxida tion proceeds in peroxisomes leading to the concept that phytanic acid oxidation in the intact cell requires the participation of both mitoc hondria and peroxisomes.