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Journal of Lipid Research, Vol. 45, 1341-1346, July 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

-Hydroxylation of phytanic acid in rat liver microsomes

J. C. Komen, M. Duran and R. J. A. Wanders¹

University of Amsterdam, Academic Medical Center, Departments of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Laboratory for Genetic Metabolic Diseases, Amsterdam, the Netherlands

¹ To whom correspondence should be addressed. e-mail: r.j.wanders{at}amc.uva.nl

The 3-methyl-branched fatty acid phytanic acid is degraded by the peroxisomal -oxidation route because the 3-methyl group blocks ß-oxidation. In adult Refsum disease (ARD), peroxisomal -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, -oxidation. The first step in -oxidation is hydroxylation at the -end of the fatty acid, catalyzed by a member of the cytochrome P450 multienzyme family. 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, - and (-1)-hydroxyphytanic acid (ratio of formation, 5:1). The formation of -hydroxyphytanic acid was NADPH dependent and inhibited by imidazole derivatives.

These results indicate that phytanic acid undergoes -hydroxylation in rat liver microsomes and that an isoform of cytochrome P450 catalyzes the first step of phytanic acid -oxidation.

Abbreviations: ARD, adult Refsum disease; TMS, trimethylsilyl

Supplementary key words fatty acids • cytochrome P450 • -oxidation

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