title: Detection of unusual very-long-chain fatty acid and ether lipid derivatives in the fibroblasts and plasma of patients with peroxisomal diseases using liquid chromatography-mass spectrometry.
abstract: Metabolic changes occur in patients with peroxisomal diseases owing to impairments in the genes involved in peroxisome function. For diagnostic purposes, saturated very-long-chain fatty acids (VLCFAs) such as C24:0 and C26:0, phytanic acid, pristanic acid, and plasmalogens are often measured as metabolic hallmarks. As the direct pathology of peroxisomal disease is yet to be fully elucidated, we sought to explore the fatty acid species that accumulate in patients with peroxisomal diseases. We developed a method for detecting a range of fatty acids implicated in peroxisomal diseases such as Zellweger syndrome (ZS) and X-linked adrenoleukodystrophy (X-ALD). To this end, we employed an ultra-performance liquid chromatography-mass spectrometry (LC-MS) coupled with negatively charged electrospray ionization. Fatty acids from patients and control subjects were extracted from total lipids by acid-hydrolysis and compared. In accordance with previous results, the amounts of VLCFAs, phytanic acid, and pristanic acid differed between the two groups. We identified extremely long and highly polyunsaturated VLCFAs (ultra-VLC-PUFAs) such as C44:12 in ZS samples. Moreover, three unknown molecules were prominent in control samples but scarcely detectable in ZS samples. LC-MS/MS analysis identified these as 1-alkyl-sn-glycerol 3-phosphates derived from ether lipids containing fatty alcohols such as C16:0, C18:0, or C18:1. Our method provides an approach to observing a wide range of lipid-derived fatty acids and related molecules in order to understand the metabolic changes involved in peroxisomal diseases. This technique can therefore be used in identifying metabolic markers and potential clinical targets for future treatment.
authors.affiliation: Division of Genomics Research, Life Science Research Center, Gifu University, Japan. Electronic address: staka@gifu-u.ac.jp.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Takashima
authors.affiliation: Division of Genomics Research, Life Science Research Center, Gifu University, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Toyoshi
authors.affiliation: Department of Biomolecular Science, Faculty of Engineering, Gifu University, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Division of Genomics Research, Life Science Research Center, Gifu University, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kajiwara
authors.affiliation: Division of Genomics Research, Life Science Research Center, Gifu University, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Honda
authors.affiliation: Division of Genomics Research, Life Science Research Center, Gifu University, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ohba
authors.affiliation: Division of Genomics Research, Life Science Research Center, Gifu University, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Takemoto
authors.affiliation: Department of Biomolecular Science, Faculty of Engineering, Gifu University, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Division of Genomics Research, Life Science Research Center, Gifu University, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimozawa
mesh_terms: D000326:Adrenoleukodystrophy / Q000378:metabolism*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004987:Ethers / Q000097:blood / Q000378:metabolism*; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000097:blood; D018901:Peroxisomal Disorders / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods; D015211:Zellweger Syndrome / Q000378:metabolism*
chemical_list: D004987:Ethers; D005227:Fatty Acids; D008055:Lipids
keywords: Peroxisomal diseases; Phytanic acid; Plasmalogens; Pristanic acid; Very-long-chain fatty acid; X-linked adrenoleukodystrophy; Zellweger syndrome