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

• DOI: 10.1194/jlr.m600050-jlr200
• Publication Date: 2006-10-03T00:40:23Z
• Authors: J. Gloerich; D.M. van den Brink; J. P.N. Ruiter; N. van Vlies; F.M. Vaz; R. J.A. Wanders; S. Ferdinandusse
• Keywords: Pharmacology; Mice, Knockout; 0303 health sciences; Phytic Acid; Reverse Transcriptase Polymerase Chain Reaction; Immunology; Immunoblotting; Farmacie(FARM); peroxisome proliferator-activated receptor α; QD415-436; fatty aldehyde dehydrogenase; Biomedische technologie en medicijnen; Overig medisch onderzoek; Biochemistry; Farmacie/Biofarmaceutische wetenschappen (FARM); Mice; 03 medical and health sciences; Pyrimidines; Phytol; branched-chain fatty acids; Animals; Homeostasis; PPAR alpha; Peroxisome Proliferators

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 alpha (PPARalpha). To investigate the metabolism of phytol and the role of PPARalpha in its regulation, wild-type and PPARalpha knockout (PPARalpha-/-) mice were fed a phytol-enriched diet or, for comparison, a diet enriched with Wy-14,643, a synthetic PPARalpha 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 PPARalpha-/- mice compared with wild-type mice. Activity measurements of the enzymes involved in phytol metabolism showed that treatment with a PPARalpha agonist resulted in a PPARalpha-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 PPARalpha and is specific for the breakdown of (E)-phytol.