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Analytical and Bioanalytical Chemistry

, Volume 407, Issue 17, pp 5045–5052 | Cite as

Evidence for an N-methyl transfer reaction in phosphatidylcholines with a terminal aldehyde during negative electrospray ionization tandem mass spectrometry

  • Ann-Charlotte Almstrand
  • Christopher Johnson
  • Robert C. MurphyEmail author
Paper in Forefront
Part of the following topical collections:
  1. Lipidomics

Abstract

Lipidomic analysis of the complex mixture of lipids isolated from biological systems can be a challenging process that often involves tandem mass spectrometry and interpretation of both precursor ions and product ions relative to the molecular structure of the lipids. Therefore, detailed understanding of the gas-phase ion chemistry occurring for each class of phospholipids is critically important for an accurate assignment of lipid structure. Some oxidized phosphatidylcholines are known to be biologically active and responsible for pathological events, and are therefore important targets for detection in lipidomic studies. Modification of fatty acyl chains by oxidation may, however, change the behavior of ion formation and decomposition in the mass spectrometer. In this study, we report on the mass-spectrometric behavior of 1-palmitoyl-2-(9′-oxononanoyl)-sn-glycero-3-phosphocholine, a bioactive product of phosphatidylcholine oxidation. In addition to [M−15] and the acetate adduct [M+59], three additional adduct ions, including [M−H], were present in significant abundance in the negative ion electrospray mass spectrum. It was found that this unexpected [M−H] ion was formed by the transfer of a methyl group from the choline residue on the polar head group to the aldehyde functionality of the sn-2 substituent, resulting in a 14-Da increase in the mass of the resulting sn-2 carboxylate anion formed by collisional activation of this ion. These results suggest additional rules for understanding the gas-phase ion chemistry of aldehydic phosphatidylcholine molecular species.

Keywords

Lipidomics Electrospray ionization Mass spectrometry Phosphatidylcholine Omega-aldehyde phosphatidylcholine Tandem mass spectrometry 

Notes

Acknowledgments

This work was supported by the Swedish Research Council Formas (210-2011-1606) and a grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health (HL034303).

Supplementary material

216_2015_8555_MOESM1_ESM.pdf (157 kb)
ESM 1 (PDF 156 kb)

References

  1. 1.
    Quehenberger O, Armando AM, Brown AH, Milne SB, Myers DS, Merrill AH, Bandyopadhyay S, Jones KN, Kelly S, Shaner RL, Sullards CM, Wang E, Murphy RC, Barkley RM, Leiker TJ, Raetz CR, Guan Z, Laird GM, Six DA, Russell DW, McDonald JG, Subramaniam S, Fahy E, Dennis EA (2010) Lipidomics reveals a remarkable diversity of lipids in human plasma. J Lipid Res 51:3299–3305CrossRefGoogle Scholar
  2. 2.
    Ivanova PT, Cerda BA, Horn DM, Cohen JS, McLafferty FW, Brown HA (2001) Electrospray ionization mass spectrometry analysis of changes in phospholipids in RBL-2H3 mastocytoma cells during degranulation. Proc Natl Acad Sci U S A 98:7152–7157CrossRefGoogle Scholar
  3. 3.
    Murphy RC, Axelsen PH (2011) Mass spectrometric analysis of long-chain lipids. Mass Spectrom Rev 30:579–599CrossRefGoogle Scholar
  4. 4.
    Harrison KA, Murphy RC (1995) Negative electrospray ionization of glycerophosphocholine lipids: formation of [M-15]- ions occurs via collisional decomposition of adduct anions. J Mass Spectrom 30:1772–1773CrossRefGoogle Scholar
  5. 5.
    Hsu FF, Lodhi IJ, Turk J, Semenkovich CF (2014) Electrospray ionization/tandem quadrupole mass spectrometric studies on phosphatidylcholines: the fragmentation process. J Am Soc Mass Spectrom 25:1412–1420CrossRefGoogle Scholar
  6. 6.
    Kayganich-Harrison KA, Murphy RC (1994) Characterization of chain-shortened oxidized glycerophosphocholine lipids using fast atom bombardment and tandem mass spectrometry. Anal Biochem 221:16–24CrossRefGoogle Scholar
  7. 7.
    Watson AD, Leitinger N, Navab M, Faull KF, Horkko S, Witztum JL, Palinski W, Schwenke D, Salomon RG, Sha W, Subbanagounder G, Fogelman AM, Berliner JA (1997) Structural identification by mass spectrometry of oxidized phospholipids in minimally oxidized low density lipoprotein that induce monocyte/endothelial interactions and evidence for their presence in vivo. J Biol Chem 272:13597–13607CrossRefGoogle Scholar
  8. 8.
    Bochkov VN (2007) Inflammatory profile of oxidized phospholipids. Thromb Haemost 97:348–354Google Scholar
  9. 9.
    Volinsky R, Kinnunen PK (2013) Oxidized phosphatidylcholines in membrane-level cellular signaling: from biophysics to physiology and molecular pathology. FEBS J 280:2806–2816CrossRefGoogle Scholar
  10. 10.
    Ou Z, Ogamo A, Guo L, Konda Y, Harigaya Y, Nakagawa Y (1995) Identification and quantitation of choline glycerophospholipids that contain aldehyde residues by fluorometric high-performance liquid chromatography. Anal Biochem 227:289–294CrossRefGoogle Scholar
  11. 11.
    Uhlson C, Harrison K, Allen CB, Ahmad S, White CW, Murphy RC (2002) Oxidized phospholipids derived from ozone treated lung surfactant extract reduce macrophage and monocyte viability. Chem Res Toxicol 15:896–906CrossRefGoogle Scholar
  12. 12.
    Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917CrossRefGoogle Scholar
  13. 13.
    Pulfer MK, Harrison K, Murphy RC (2004) Direct electrospray tandem mass spectrometry of the unstable hydroperoxy bishemiacetal product derived from cholesterol ozonolysis. J Am Soc Mass Spectrom 15:194–202CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Ann-Charlotte Almstrand
    • 1
    • 2
  • Christopher Johnson
    • 1
  • Robert C. Murphy
    • 1
    Email author
  1. 1.Department of PharmacologyUniversity of Colorado DenverAuroraUSA
  2. 2.Department of Public Health and Community MedicineUniversity of GothenburgGothenburgSweden

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