Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8302430 | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2014 | 10 Pages |
Abstract
Peroxisomes are subcellular organelles that function in multiple anabolic and catabolic processes, including β-oxidation of very-long-chain fatty acids (VLCFA) and biosynthesis of ether phospholipids. Peroxisomal disorders caused by defects in peroxisome biogenesis or peroxisomal β-oxidation manifest as severe neural disorders of the central nervous system. Abnormal peroxisomal metabolism is thought to be responsible for the clinical symptoms of these diseases, but their molecular pathogenesis remains to be elucidated. We performed lipidomic analysis to identify aberrant metabolites in fibroblasts from patients with Zellweger syndrome (ZS), acyl-CoA oxidase1 (AOx) deficiency, D-bifunctional protein (D-BP) and X-linked adrenoleukodystrophy (X-ALD), as well as in peroxisome-deficient Chinese hamster ovary cell mutants. In cells deficient in peroxisomal biogenesis, plasmenylethanolamine was remarkably reduced and phosphatidylethanolamine was increased. Marked accumulation of very-long-chain saturated fatty acid and monounsaturated fatty acids in phosphatidylcholine was observed in all mutant cells. Very-long-chain polyunsaturated fatty acid (VLC-PUFA) levels were significantly elevated, whilst phospholipids containing docosahexaenoic acid (DHA, C22:6n-3) were reduced in fibroblasts from patients with ZS, AOx deficiency, and D-BP deficiency, but not in fibroblasts from an X-ALD patient. Because patients with AOx deficiency suffer from more severe symptoms than those with X-ALD, accumulation of VLC-PUFA and/or reduction of DHA may be associated with the severity of peroxisomal diseases.
Keywords
plasmenylethanolamineABCD1d-bifunctional proteinPtdChoPBDPlsEtnAOXSFAMUFALC-ESI-MS/MSPtdEtnsiRNAperoxisome biogenesis disorderArachidonic acidOleic aciddocosahexaenoic acidsaturated fatty acidmonounsaturated fatty acidPolyunsaturated fatty acidPUFAChoChinese Hamster OvaryCNSDHAcentral nervous systemphosphatidylcholinephosphatidylethanolamineComplementation group
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Yuichi Abe, Masanori Honsho, Hiroki Nakanishi, Ryo Taguchi, Yukio Fujiki,