title: Metabolism of phytol to phytanic acid in the mouse, and the role of PPARalpha in its regulation.
abstract: 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.
authors.affiliation: Laboratory of Genetic Metabolic Diseases, Department of Clinical Chemistry, Emma's Children's Hospital, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Gloerich
authors.forename: D M
authors.initials: DM
authors.lastname: van den Brink
authors.forename: J P N
authors.initials: JP
authors.lastname: Ruiter
authors.forename: N
authors.initials: N
authors.lastname: van Vlies
authors.forename: F M
authors.initials: FM
authors.lastname: Vaz
authors.forename: R J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: S
authors.initials: S
authors.lastname: Ferdinandusse
mesh_terms: D000818:Animals; D006706:Homeostasis; D015151:Immunoblotting; D051379:Mice; D018345:Mice, Knockout; D047493:PPAR alpha / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D020025:Peroxisome Proliferators / Q000494:pharmacology; D010833:Phytic Acid / Q000378:metabolism*; D010836:Phytol / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D047493:PPAR alpha; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D010836:Phytol; D010833:Phytic Acid; C006253:pirinixic acid