Issue 46, 2019

A lipidomic workflow capable of resolving sn- and C[double bond, length as m-dash]C location isomers of phosphatidylcholines

Abstract

As a major class of mammalian lipids, phosphatidylcholines (PCs) often contain mixtures of structural isomers, resulting from different lipogenesis pathways. Profiling PCs at the isomer level, however, remains challenging in lipidomic settings, especially for characterizing the positions of fatty acyls on the glycerol backbone (sn-positions) and the locations of carbon–carbon double bonds (C[double bond, length as m-dash]Cs) in unsaturated acyl chains. In this work, we have developed a workflow for profiling PCs down to sn- and C[double bond, length as m-dash]C locations at high coverage and sensitivity. This capability is enabled by radical-directed fragmentation, forming sn-1 specific fragment ions upon collision-induced dissociation (CID) of bicarbonate anion adducts of PCs ([M + HCO3]) inside a mass spectrometer. This new tandem mass spectrometry (MS/MS) method can be simply incorporated into liquid chromatography by employing ammonium bicarbonate in the mobile phase without any instrument modification needed. It is also compatible with the online Paternò–Büchì reaction and subsequent MS/MS for the assignment of C[double bond, length as m-dash]C locations in sn-1 fatty acyl chains of unsaturated PCs. The analytical performance of the workflow is manifested by identification of 82 distinct PC molecular species from the polar extract of bovine liver, including quantification of 19 pairs of sn-isomers. Finally, we demonstrate that five pairs of PC sn-isomers show significant compositional changes in tissue samples of human breast cancer relative to controls, suggesting a potential for monitoring PC sn-isomers for biomedical applications.

Graphical abstract: A lipidomic workflow capable of resolving sn- and C [[double bond, length as m-dash]] C location isomers of phosphatidylcholines

Supplementary files

Article information

Article type
Edge Article
Submitted
17 Jul 2019
Accepted
04 Oct 2019
First published
07 Oct 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2019,10, 10740-10748

A lipidomic workflow capable of resolving sn- and C[double bond, length as m-dash]C location isomers of phosphatidylcholines

X. Zhao, W. Zhang, D. Zhang, X. Liu, W. Cao, Q. Chen, Z. Ouyang and Y. Xia, Chem. Sci., 2019, 10, 10740 DOI: 10.1039/C9SC03521D

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