Gloerich J, van den Brink D M, Ruiter J P N, van Vlies N, Vaz F M, Wanders R J A, Ferdinandusse S
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.
J Lipid Res. 2007 Jan;48(1):77-85. doi: 10.1194/jlr.M600050-JLR200. Epub 2006 Oct 2.
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.
叶绿醇是一种支链脂肪醇，是植烷酸和降植烷酸这两种支链脂肪酸的天然前体，而这两种支链脂肪酸都是核激素受体过氧化物酶体增殖物激活受体α（PPARα）的配体。为了研究叶绿醇的代谢及其调控过程中PPARα的作用，给野生型和PPARα基因敲除（PPARα-/-）小鼠喂食富含叶绿醇的饮食，或者作为对照，喂食富含合成PPARα激动剂Wy-14,643的饮食。在喂食富含叶绿醇的饮食后，仅在摄取部位小肠和肝脏中检测到叶绿醇。随着饮食时间延长，与野生型小鼠相比，PPARα-/-小鼠肝脏中叶绿醇的（E）-异构体水平显著增加。参与叶绿醇代谢的酶活性测量结果表明，用PPARα激动剂处理会导致肝脏中叶绿醇降解途径至少两个步骤的PPARα依赖性诱导。此外，所涉及的酶对其各自底物的（E）-异构体的活性高于（Z）-异构体，表明对（E）-叶绿醇代谢具有立体特异性。总之，此处描述的结果表明，叶绿醇向植烷酸的转化通过PPARα进行调节，并且对（E）-叶绿醇的分解具有特异性。
