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.
Department of Clinical Biochemistry, University Hospital Amsterdam, The Netherlands.
R J
RJ
Wanders
C W
CW
Van Roermund
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