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Journal of Lipid Research, Vol. 48, 77-85, January 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Metabolism of phytol to phytanic acid in the mouse, and the role of PPAR in its regulation

J. Gloerich, D. M. van den Brink, J. P. N. Ruiter, N. van Vlies, F. M. Vaz, R. J. A. Wanders and S. Ferdinandusse¹

Laboratory of Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma's Children's Hospital, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands

Published, JLR Papers in Press, October 2, 2006.

¹ To whom correspondence should be addressed. e-mail: s.ferdinandusse{at}amc.uva.nl

Phytol, a branched-chain fatty alcohol, is the naturally occurring precursor of phytanic and pristanic acid, branched-chain fatty acids that are both ligands for the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR). To investigate the metabolism of phytol and the role of PPAR in its regulation, wild-type and PPAR knockout (PPAR^–/–) mice were fed a phytol-enriched diet or, for comparison, a diet enriched with Wy-14,643, a synthetic PPAR agonist. After the phytol-enriched diet, phytol could only be detected in small intestine, the site of uptake, and liver. Upon longer duration of the diet, the level of the (E)-isomer of phytol increased significantly in the liver of PPAR^–/– mice compared with wild-type mice. Activity measurements of the enzymes involved in phytol metabolism showed that treatment with a PPAR agonist resulted in a PPAR-dependent induction of at least two steps of the phytol degradation pathway in liver. Furthermore, the enzymes involved showed a higher activity toward the (E)-isomer than the (Z)-isomer of their respective substrates, indicating a stereospecificity toward the metabolism of (E)-phytol. In conclusion, the results described here show that the conversion of phytol to phytanic acid is regulated via PPAR and is specific for the breakdown of (E)-phytol.

Supplementary key words peroxisome proliferator-activated receptor • fatty aldehyde dehydrogenase • branched-chain fatty acids

Abbreviations: FALDH, fatty aldehyde dehydrogenase; MBP, maltose binding protein; MTBSTFA, N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide; PPAR, peroxisome proliferator-activated receptor

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