Functional characterisation of peroxisomal ß-oxidation disorders in fibroblasts using lipidomics.
J Inherit Metab Dis
; 41(3): 479-487, 2018 05.
Article
en En
| MEDLINE
| ID: mdl-28849344
ABSTRACT
Peroxisomes play an important role in a variety of metabolic pathways, including the α- and ß-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 ß-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 ß-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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Trastorno Peroxisomal
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Metabolómica
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Fibroblastos
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Lípidos
Tipo de estudio:
Observational_studies
Límite:
Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article