Abstract
Glycosphingolipids (GSLs) contain one or more sugars that are attached to a sphingolipid moiety, usually to a ceramide, but in rare cases also to a sphingoid base. A large structural heterogeneity results from differences in number, identity, linkage, and anomeric configuration of the carbohydrate residues, and also from structural differences within the hydrophobic part. GSLs form complex cell-type specific patterns, which change with the species, the cellular differentiation state, viral transformation, ontogenesis, and oncogenesis. Although GSL structures can be assigned to only a few series with a common carbohydrate core, their structural variety and the complex pattern are challenges for their elucidation and quantification by mass spectrometric techniques. We present a general overview of the application of lipidomics for GSL determination. This includes analytical procedures and instrumentation together with recent correlations of GSL molecular species with human diseases. Difficulties such as the structural complexity and the lack of standard substances for complex GSLs are discussed.
Highlights
Within systems biology, lipidomics is the discipline that creates, analyzes, and integrates complex data on the lipidome of so-called systems
Mass spectrometry has revolutionized the analysis oflipids and allowed the emergence of the field of “lipidomics”, which aims at a comprehensive analysis of thelipidome in a given system
This step is even more critical than the extraction of other lipid classes: Early work revealed that recovery of GSLs is improved if small amounts of water are present in the extraction solvent [52]
Summary
Lipidomics is the discipline that creates, analyzes, and integrates complex data on the lipidome of so-called systems. Despite their various roles in human health and disease, GSL analysis is often neglected or incompletely addressed within “omics” approaches, even in lipidomics [4,5] and glycomics This is mainly due to the structural complexity and diversity of cellular glycolipids, and to differences in abundance, chemical stability, and biophysical properties between the analytes. Sialic acids can be attached to several galactosyl residues within the core structures of the ganglio-, lacto-, and neolacto-series, and to GalCer (ganglioside GM4; Figure 2) They can be further modified by acylation of different alcohol groups [15], or by lactonisation [16] (Figure 3). Very little is known about how this part of the lipidome changes with disease states and how it influences human health
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