Studies on phytanic acid alpha-oxidation in rat liver and cultured human skin fibroblasts.
We have studied the alpha-oxidation of phytanic acid in rat liver and human skin fibroblasts in order to try to resolve the controversial issue of the subcellular site of alpha-oxidation of phytanic acid. The results show that isolated mitochondria are able to alpha-oxidize phytanic acid whereas isolated peroxisomes show no phytanic acid alpha-oxidation activity. Intact hepatocytes were found to alpha-oxidize phytanic acid at a rate which is more than 20-fold higher than the activity found in postnuclear supernatant fractions incubated under optimal conditions. The alpha-oxidation of phytanic acid was found to be sensitive to inhibitors of the respiratory chain and an uncoupler of oxidative phosphorylation. Furthermore, the alpha-oxidation of phytanic acid was found to be deficient in cultured human skin fibroblasts with an inherited deficiency of cytochrome c oxidase and in fibroblasts with a deficiency of functional peroxisomes. We conclude that mitochondria are indispensable for phytanic acid alpha-oxidation. Furthermore, we propose that one (or more) of the partial reactions in phytanic acid alpha-oxidation proceeds in peroxisomes leading to the concept that phytanic acid oxidation in the intact cell requires the participation of both mitochondria and peroxisomes.
Wanders
R J
RJ
Department of Clinical Biochemistry, University Hospital Amsterdam, The Netherlands.
Van Roermund
C W
CW
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured / Q000378:metabolism; D030401:Cytochrome-c Oxidase Deficiency; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008830:Microbodies / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010831:Phytanic Acid / Q000378:metabolism*; D051381:Rats; D012867:Skin / Q000378:metabolism*
D010831:Phytanic Acid; D000255:Adenosine Triphosphate