title: Molecular species of phospholipids with very long chain fatty acids in skin fibroblasts of Zellweger syndrome.
abstract: The ratio of C 26:0/C 22:0 fatty acids in patient lipids is widely accepted as a critical clinical criterion of peroxisomal diseases, such as Zellweger syndrome and X-linked adrenoleukodystrophy (X-ALD). However, phospholipid molecular species with very long chain fatty acids (VLCFA) have not been precisely characterized. In the present study, the structures of such molecules in fibroblasts of Zellweger syndrome and X-ALD were examined using LC-ESI-MS/MS analysis. In fibroblasts from Zellweger patients, a large number of VLCFA-containing molecular species were detected in several phospholipid classes as well as neutral lipids, including triacylglycerol and cholesteryl esters. Among these lipids, phosphatidylcholine showed the most diversity in the structures of VLCFA-containing molecular species. Some VLCFA possessed longer carbon chains and/or larger number of double bonds than C 26:0-fatty acid (FA). Similar VLCFA were also found in other phospholipid classes, such as phosphatidylethanolamine and phosphatidylserine. In addition, VLCFA-containing phospholipid species showed some differences among fibroblasts from Zellweger patients. It appears that phospholipids with VLCFA, with or without double bonds, as well as C 26:0-FA might affect cellular functions, thus leading to the pathogenesis of peroxisomal diseases, such as Zellweger syndrome and X-ALD.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hama
authors.forename: Toru
authors.initials: T
authors.lastname: Nagai
authors.forename: Chiho
authors.initials: C
authors.lastname: Nishizawa
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
authors.forename: Masashi
authors.initials: M
authors.lastname: Morita
authors.forename: Noriko
authors.initials: N
authors.lastname: Satoh
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Imanaka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shimozawa
authors.forename: Ryo
authors.initials: R
authors.lastname: Taguchi
authors.forename: Keizo
authors.initials: K
authors.lastname: Inoue
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Yokoyama
mesh_terms: D000326:Adrenoleukodystrophy / Q000378:metabolism / Q000503:physiopathology; D005227:Fatty Acids / Q000032:analysis / Q000737:chemistry*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D010713:Phosphatidylcholines / Q000032:analysis / Q000378:metabolism; D010743:Phospholipids / Q000032:analysis / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods; D015211:Zellweger Syndrome / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D005227:Fatty Acids; D010713:Phosphatidylcholines; D010743:Phospholipids