PhytanoylâCoA hydroxylase activity is induced by phytanic acid
2000
Zomer, Anna W. M. | Jansen, Gerbert A. | van der Burg, Bart | Verhoeven, Nanda M. | Jakobs, Cornelis | van der Saag, Paul T. | Wanders, Ronald J. A. | PollâThe, Bwee Tien
Phytanic acid (3,7,11,15âtetramethylhexadecanoic acid) is a branchedâchain fatty acid present in various dietary products such as milk, cheese and fish. In patients with Refsum disease, accumulation of phytanic acid occurs due to a deficiency of phytanoylâCoA hydroxylase, a peroxisomal enzyme containing a peroxisomal targeting signal 2. Recently, phytanoylâCoA hydroxylase cDNA has been isolated and functional mutations have been identified. As it has been shown that phytanic acid activates the nuclear hormone receptors peroxisome proliferatorâactivated receptor (PPAR)α and all three retinoid X receptors (RXRs), the intracellular concentration of this fatty acid should be tightly regulated. When various cell lines were grown in the presence of phytanic acid, the activity of phytanoylâCoA hydroxylase increased up to four times, depending on the particular cell type. In one cell line, HepG2, no induction of phytanoylâCoA hydroxylase activity was observed. After addition of phytanic acid to COSâ1 cells, an increase in phytanoylâCoA hydroxylase activity was observed within 2âh, indicating a quick cell response. No stimulation of phytanoylâCoA hydroxylase was observed when COSâ1 cells were grown in the presence of clofibric acid, 9âcisâretinoic acid or both ligands together. This indicates that the activation of phytanoylâCoA hydroxylase is not regulated via PPARα or RXR. However, stimulation of PPARα and all RXRs by clofibric acid and 9âcisâretinoic acid was observed in transient transfection assays. These results suggest that the induction of phytanoylâCoA hydroxylase by phytanic acid does not proceed via one of the nuclear hormone receptors, RXR or PPARα.
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