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.