出版社：American Society for Biochemistry and Molecular Biology
摘要：Phytol, a branched-chain fatty alcohol, is the naturally occurringprecursor of phytanic and pristanic acid, branched-chain fattyacids that are both ligands for the nuclear hormone receptorperoxisome proliferator-activated receptor (PPAR). To investigatethe metabolism of phytol and the role of PPAR in its regulation,wild-type and PPAR knockout (PPAR–/–) mice werefed a phytol-enriched diet or, for comparison, a diet enrichedwith Wy-14,643, a synthetic PPAR agonist. After the phytol-enricheddiet, phytol could only be detected in small intestine, thesite of uptake, and liver. Upon longer duration of the diet,the level of the (E)-isomer of phytol increased significantlyin the liver of PPAR–/– mice compared with wild-typemice. Activity measurements of the enzymes involved in phytolmetabolism showed that treatment with a PPAR agonist resultedin a PPAR-dependent induction of at least two steps of the phytoldegradation pathway in liver. Furthermore, the enzymes involvedshowed a higher activity toward the (E)-isomer than the (Z)-isomerof their respective substrates, indicating a stereospecificitytoward the metabolism of (E)-phytol. In conclusion, the resultsdescribed here show that the conversion of phytol to phytanicacid is regulated via PPAR and is specific for the breakdownof (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
(PPAR
