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Oral Sessions
Day 4, June 25（Wed.） 13:55-14:10
Room C (Top of Yaima)
- 4C-O2-1355
Profiling of the Low-Abundance Lipidome by Selective Enrichment and Isomer-Resolved Tandem Mass Spectrometry
(Tsinghua Univ.)
Zidang Wang, Yichun Wang, oYu Xia
The lipidome consists of thousands of distinct lipid species, with concentrations spanning at least eight orders of magnitude. However, low abundance lipid classes, which typically constitute less than 1% of total lipid mass, stand outside the dynamic range allowed from conventional lipidomic analsysis workflows. Herein, we have developed selective enrichment methods for neutral glycosphingolipids (nGSL) and gangliosides, respectively, using magnetic titanium dioxide nanoparticles (TiO₂ MNPs).1,2 These methods rely on forming strong coordination between the cis-diol of the glycan headgroup with Ti (IV) under basic pH conditions. Under these conditions, the interfering phospholipids only form weak electronic interactions with Ti (IV) which can be subsequently removed with a washing buffer containing ammonium salt. These methods achieve 30- to 100-fold enrichment of nGSLs and gangliosides, with detection limits in the sub-nM range. By combining selective enrichment with charge-tagging Paternò–Büchi reaction, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, we identify over 600 distinct structures of nGSLs and gangliosides from porcine brain lipid extract and human plasma at multiple structural levels, including subclass, species, chain composition, and double bond location. These deep-profiling workflows also reveal dysregulated metabolism of nGSLs and gangliosides in human glioma tissue and breast cancer cells.