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J Inherit Metab Dis. 2018 May;41(3):479-487. doi: 10.1007/s10545-017-0076-9. Epub 2017 Aug 28.

Functional characterisation of peroxisomal β-oxidation disorders in fibroblasts using lipidomics.

Author information

1
Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.
2
Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.
3
Biosystems Data Analysis, Swammerdam Institute for Life Sciences, University of Amsterdam, Science Park 904, Amsterdam, 1098 XH, The Netherlands.
4
Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands. h.r.waterham@amc.uva.nl.
5
Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands. f.m.vaz@amc.uva.nl.

Abstract

Peroxisomes play an important role in a variety of metabolic pathways, including the α- and β-oxidation of fatty acids, and the biosynthesis of ether phospholipids. Single peroxisomal enzyme deficiencies (PEDs) are a group of peroxisomal disorders in which either a peroxisomal matrix enzyme or a peroxisomal membrane transporter protein is deficient. To investigate the functional consequences of specific enzyme deficiencies on the lipidome, we performed lipidomics using cultured skin fibroblasts with different defects in the β-oxidation of very long-chain fatty acids, including ABCD1- (ALD), acyl-CoA oxidase 1 (ACOX1)-, D-bifunctional protein (DBP)-, and acyl-CoA binding domain containing protein 5 (ACBD5)-deficient cell lines. Ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry revealed characteristic changes in the phospholipid composition in fibroblasts with different fatty acid β-oxidation defects. Remarkably, we found that ether phospholipids, including plasmalogens, were decreased. We defined specific phospholipid ratios reflecting the different enzyme defects, which can be used to discriminate the PED fibroblasts from healthy control cells.

KEYWORDS:

Lipidomics; Peroxisomes; Phospholipids; Plasmalogens; Very long-chain fatty acids; β-oxidation

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