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.

Lipidomic analysis of fibroblasts from Zellweger spectrum disorder patients identifies disease-specific phospholipid ratios

“…The upregulation of PE in combination with a decrease in PE ether phospholipid levels has also been reported in fibroblasts derived from RCDP and severe ZSD patients (25,26). Finally, we found an accumulation of SM species with C26 and C28 in severe ZSD patients, which was also observed in an earlier study with fibroblasts from severe ZSD patients (27).…”

Profiling and Imaging of Phospholipids in Brains of Abcd1‐Deficient Mice

“…The first feature is that VLCFA are mostly incorporated at the sn‐ 1 position of PtdCho and PtdEtn (Table ). This result is consistent with our previous lipid analysis on a fission yeast mutant and fibroblasts from Zellweger patients, both of which accumulate VLCFA (Hama et al, ; Yokoyama et al, ). Possible machinery responsible for these observations are phospholipase A 1 and acyltransferases cooperatively exchanging fatty acids into VLCFA at the sn ‐1 position.…”

Lipidomic profile in three species of dinoflagellates ( Amphidinium carterae , Cystodinium sp., and Peridinium aciculiferum ) containing very long chain polyunsaturated fatty acids

“…Tandem MS has recently been successfully used (Berdeaux et al, 2010;Hama et al, 2013) to show that all diacylphospholipid molecular species in skin fibroblasts of Zellweger syndrome contained only one VLCFA in their DAG moieties and they were mostly found in the sn-1 position. This suggested that some acyltransferases responsible for sn-1 position acylation preferred certain VLCFA or that some VLCFAselective acyltransferases possessed higher affinity for the sn-1 than the sn-2 position.…”