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A more recent version of this article appeared on July 1, 2004

Papers In Press, published online ahead of print April 21, 2004
J. Lipid Res., doi:10.1194/jlr.M400064-JLR200
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Submitted on February 17, 2004
Revised on April 13, 2004
Accepted on April 17, 2004

{omega}-Hydroxylation of phytanic acid in rat liver microsomes: Implications for Refsum disease

J. C. Komen, M. Duran, and R. J. A. Wanders

Clinical chemistry and Pediatrics, Academic Medical Center, Amsterdam, N-Holland 1105 AZ

Corresponding Author: r.j.wanders{at}amc.uva.nl

The 3-methyl-branched fatty acid phytanic acid is degraded by the peroxisomal {alpha}-oxidation route since the 3-methyl group blocks {beta}-oxidation. In Adult Refsum Disease (ARD) peroxisomal {alpha}-oxidation is defective, which is caused by mutations in the gene coding for phytanoyl-CoA hydroxylase in the majority of ARD patients. As a consequence, phytanic acid accumulates in tissues and body fluids. This study focuses on an alternative route of phytanic acid degradation, i.e. {omega}-oxidation. The first step in {omega}-oxidation is hydroxylation at the {omega}-end of the fatty acid, catalyzed by a member of the cytochrome P450 multi-enzyme family. In order to study this first step, the formation of hydroxylated intermediates was studied in rat liver microsomes incubated with phytanic acid and NADPH. Two hydroxylated metabolites of phytanic acid were formed, viz. {omega}- and ({omega}-1)-hydroxyphytanic acid (ratio of formation 5:1). Formation of {omega}-hydroxyphytanic acid was NADPH dependent and inhibited by imidazole derivatives. These results indicate that phytanic acid undergoes {omega}-hydroxylation in rat liver microsomes and that an isoform of cytochrome P450 catalyzes the first step of phytanic acid {omega}-oxidation.


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