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High-Throughput Metabolomics pp 81–105Cite as

Overview of Lipid Mass Spectrometry and Lipidomics

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1978))

Abstract

Mass spectrometry has played a critical role in the identification and quantitation of lipids present in biological extracts. Various strategies have emerged in order to carry out lipidomic studies. These include both shotgun approaches as well as those engaging liquid chromatographic separation of lipid species prior to mass spectrometric analysis. Nonetheless challenges remain at every level of the lipidomic experiment, including extraction of lipids, identification of specific species, and quantitation of the vast array of lipids present in the sample extract. New strategies have emerged to address some of these issues; however, precise quantitation remains a significant challenge. The use of the ratio of the abundance of the molecular ion species to that of an internal standard enables quite accurate assessment of fold changes within complex lipid species without the need for exact quantitation. Challenges continue to remain in terms of availability of reference standard material as well as relevant internal standards.

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References

  1. Fahy E, Subramaniam S, Brown HA, Glass CK, Merrill AH Jr, Murphy RC, Raetz CRH, Russell DW, Seyama Y, Shaw W, Shimizu T, Spener F, van Meer G, VanNieuwenhze MS, White SH, Witztum JL, Dennis EA (2005) A comprehensive classification system for lipids. J Lipid Res 46:839–862

    Article  CAS  PubMed  Google Scholar 

  2. Chilton FH, Murphy RC, Wilson BA, Sergeant S, Ainsworth H, Seeds MC, Mathias RA (2014) Diet-gene interactions and PUFA metabolism: a potential contributor to health disparities and human diseases. Nutrients 6:1993–2022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Jakobsson A, Westerberg R, Jacobsson A (2006) Fatty acid elongases in mammals: their regulation and roles in metabolism. Prog Lipid Res 45:237–249

    Article  CAS  PubMed  Google Scholar 

  4. Fagone P, Jackowski S (2009) Membrane phospholipid synthesis and endoplasmic reticulum function. J Lipid Res 50:S311–S316

    Article  PubMed  PubMed Central  Google Scholar 

  5. Yamashita A, Hayashi Y, Nemoto-Sasaki Y, Ito M, Oka S, Tanikawa T, Waku K, Sugiura T (2014) Acyltransferases and transacylases that determine the fatty acid composition of glycerolipids and the metabolism of bioactive lipid mediators in mammalian cells and model organisms. Prog Lipid Res 53:18–81

    Article  CAS  PubMed  Google Scholar 

  6. Duan J, Merrill AH Jr (2015) 1-Deoxysphingolipids encountered exogenously and made de novo: dangerous mysteries inside an enigma. J Biol Chem 90:15380–15389

    Article  Google Scholar 

  7. Maceyka M, Harikumar KB, Milstien S, Spiegel S (2012) Sphingosine-1-phosphate signaling and its role in disease. Trends Cell Biol 22:50–60

    Article  CAS  PubMed  Google Scholar 

  8. Merrill AH Jr (2011) Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics. Chem Rev 111:6387–6422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fitzgerald M, Murphy RC (2007) Electrospray mass spectrometry of human hair wax esters. J Lipid Res 48:1231–1246

    Article  CAS  PubMed  Google Scholar 

  10. Sarafian MH, Lewis MR, Pechlivanis A, Ralphs S, McPhail MJ, Patel VC, Dumas ME, Holmes E, Nicholson JK (2015) Bile acid profiling and quantification in biofluids using ultra-performance liquid chromatography tandem mass spectrometry. Anal Chem 87:9662–9670

    Article  CAS  PubMed  Google Scholar 

  11. Lu W, Su X, Klein MS, Lewis IA, Fiehn O, Rabinowitz JD (2017) Metabolite measurement: pitfalls to avoid and practices to follow. Annu Rev Biochem 20:277–304

    Article  Google Scholar 

  12. 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 51:3299–3305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917

    Article  CAS  PubMed  Google Scholar 

  14. Lebaron FN, Folch J (1959) The effect of pH and salt concentration on aqueous extraction of brain proteins and lipoproteins. J Neurochem 4:1–8

    Article  CAS  PubMed  Google Scholar 

  15. Hutchins PM, Barkley RM, Murphy RC (2008) Separation of cellular non–polar neutral lipids by normal phase chromatography and analysis by electrospray ionization mass spectrometry. J Lipid Res 49:804–813

    Article  CAS  PubMed  Google Scholar 

  16. Murphy RC (2015) Tandem mass spectrometry of lipids: molecular analysis of complex lipids. In: Gaskell S (ed) New developments in mass spectrometry. Royal Society of Chemistry, London

    Google Scholar 

  17. McAnoy AM, Wu CC, Murphy RC (2005) Direct qualitative analysis of triacylglycerols by electrospray mass spectrometry using a linear ion trap. J Am Soc Mass Spectrom 16:1498–1509

    Article  CAS  PubMed  Google Scholar 

  18. Hutchins PM, Murphy RC (2011) Peroxide bond driven dissociation of hydroperoxy-cholesterol esters following collision induced dissociation. J Am Soc Mass Spectrom 22:867–874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Williams TM, Kind AJ, Houghton E, Hill DW (1999) Electrospray collision-induced dissociation of testosterone and testosterone hydroxy analogs. J Mass Spectrom 34:206–216

    Article  CAS  PubMed  Google Scholar 

  20. Wooding KM, Barkley RM, Hankin JA, Johnson CA, Bradford AP, Santoro N, Murphy RC (2013) Mechanism of formation of the major estradiol product ions following collisional activation of the molecular anion in a tandem quadrupole mass spectrometer. J Am Soc Mass Spectrom 24:1451–1455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kita Y, Tokuoka SM, Shimizu T (2017) Mediator lipidomics by liquid chromatography-tandem mass spectrometry. Biochim Biophys Acta 1862:777–781

    Article  CAS  Google Scholar 

  22. Murphy RC, Barkley RM, Zemski Berry K, Hankin JA, Harrison K, Johnson C, Krank J, McAnoy A, Uhlson C, Zarini S (2005) Electrospray ionization and tandem mass spectrometry of eicosanoids. Anal Biochem 346:1–42

    Article  CAS  PubMed  Google Scholar 

  23. Björkhem I (1979) Selective ion monitoring in clinical chemistry. CRC Crit Rev Clin Lab Sci 11:53–105

    Article  PubMed  Google Scholar 

  24. Zarini S, Gijón MA, Ransome AE, Murphy RC, Sala A (2009) Transcellular biosynthesis of leukotrienes in vivo during mouse peritoneal inflammation. Proc Natl Acad Sci U S A 106:8296–8301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sales S, Knittelfelder O, Shevchenko A (2017) Lipidomics of human blood plasma by high-resolution shotgun mass spectrometry. Methods Mol Biol 1619:203–212

    Article  CAS  PubMed  Google Scholar 

  26. Han X, Gross RW (2003) Global analyses of cellular lipidomes directly from crude extracts of biological samples by ESI mass spectrometry: a bridge to lipidomics. J Lipid Res 44:1071–1079

    Article  CAS  PubMed  Google Scholar 

  27. Hankin JA, Murphy RC, Barkley RM, Gijón MA (2015) Ion mobility and tandem mass spectrometry of phosphatidylglycerol and bis(monoacylglycerol)phosphate (BMP). Intl J Mass Spectrom 378:255–263

    Article  CAS  Google Scholar 

  28. Han X, Yang K, Gross RW (2012) Multi-dimensional mass spectrometry-based shotgun lipidomics and novel strategies for lipidomic analyses. Mass Spectrom Rev 31:134–178

    Article  CAS  PubMed  Google Scholar 

  29. Norris JL, Caprioli RM (2013) Analysis of tissue specimens by matrix-assisted laser desorption/ionization imaging mass spectrometry in biological and clinical research. Chem Rev 113:2309–2342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hájek R, Jirásko R, Lísa M, Cífková E, Holčapek M (2017) Hydrophilic interaction liquid chromatography-mass spectrometry characterization of gangliosides in biological samples. Anal Chem 89:12425–12432

    Article  PubMed  Google Scholar 

  31. Bowden JA, Heckert A, Ulmer CZ, Jones CM, Koelmel JP, Abdullah L, Ahonen L, Alnouti Y, Armando AM, Asara JM, Bamba T, Barr JR, Bergquist J, Borchers CH, Brandsma J, Breitkopf SB, Cajka T, Cazenave-Gassiot A, Checa A, Cinel MA, Colas RA, Cremers S, Dennis EA, Evans JE, Fauland A, Fiehn O, Gardner MS, Garrett TJ, Gotlinger KH, Han J, Huang Y, Neo AH, Hyötyläinen T, Izumi Y, Jiang H, Jiang H, Jiang J, Kachman M, Kiyonami R, Klavins K, Klose C, Köfeler HC, Kolmert J, Koal T, Koster G, Kuklenyik Z, Kurland IJ, Leadley M, Lin K, Maddipati KR, McDougall D, Meikle PJ, Mellett NA, Monnin C, Moseley MA, Nandakumar R, Oresic M, Patterson R, Peake D, Pierce JS, Post M, Postle AD, Pugh R, Qiu Y, Quehenberger O, Ramrup P, Rees J, Rembiesa B, Reynaud D, Roth MR, Sales S, Schuhmann K, Schwartzman ML, Serhan CN, Shevchenko A, Somerville SE, St John-Williams L, Surma MA, Takeda H, Thakare R, Thompson JW, Torta F, Triebl A, Trötzmüller M, Ubhayasekera SJK, Vuckovic D, Weir JM, Welti R, Wenk MR, Wheelock CE, Yao L, Yuan M, Zhao XH, Zhou S (2017) Harmonizing lipidomics: NIST interlaboratory comparison exercise for lipidomics using SRM 1950-metabolites in frozen human plasma. J Lipid Res 58:2275–2288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hinz C, Liggi S, Griffin JL (2017) The potential of ion mobility mass spectrometry for high-throughput and high-resolution lipidomics. Curr Opin Chem Biol 42:42–50

    Article  PubMed  Google Scholar 

  33. Liebisch G, Vizcaíno JA, Köfeler H, Trötzmüller M, Griffiths WJ, Schmitz G, Spener F, Wakelam MJ (2013) Shorthand notation for lipid structures derived from mass spectrometry. J Lipid Res 54:1523–1530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Poad BLJ, Zheng X, Mitchell TW, Smith RD, Baker ES, Blanksby SJ (2018) Online Ozonolysis combined with ion mobility-mass spectrometry provides a new platform for lipid isomer analyses. Anal Chem 90:1292–1300

    Article  CAS  PubMed  Google Scholar 

  35. Ma X, Chong L, Tian R, Shi R, Hu TY, Ouyang Z, Xia Y (2016) Proc Natl Acad Sci U S A 113:2573–2578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wall VZ, Barnhart S, Kramer F, Kanter JE, Vivekanandan-Giri A, Pennathur S, Bolego C, Ellis JM, Gijón MA, Wolfgang MJ, Bornfeldt KE (2017) Inflammatory stimuli induce acyl-CoA thioesterase 7 and remodeling of phospholipids containing unsaturated long (≥C20)-acyl chains in macrophages. J Lipid Res 58:1174–1185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Schwudke D, Shevchenko A, Hoffmann N, Ahrends R (2017) Lipidomics informatics for life-science. J Biotechnol 261:131–136

    Article  CAS  PubMed  Google Scholar 

  38. Checa A, Bedia C, Jaumot J (2015) Lipidomic data analysis: tutorial, practical guidelines and applications. Anal Chim Acta 885:1–16

    Article  CAS  PubMed  Google Scholar 

  39. Okuno T, Gijon MA, Zarini S, Martin SA, Barkley RM, Johnson CA, Ohba M, Yokomizo T, Murphy RC (2018) Altered eicosanoid production and phospholipid remodeling during cell culture. J Lipid Res 59:542–549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

Studies that led to the development of these ideas were supported in part by grants from the National Institutes of Health (HL117798, HL34303, and ES022172) and a grant from the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS).

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Authors and Affiliations

  1. Department of Pharmacology, University of Colorado Denver, Aurora, CO, USA

    Simona Zarini, Robert M. Barkley, Miguel A. Gijón & Robert C. Murphy

Authors
  1. Simona Zarini
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  2. Robert M. Barkley
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  3. Miguel A. Gijón
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  4. Robert C. Murphy
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Corresponding author

Correspondence to Robert C. Murphy .

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Editors and Affiliations

  1. Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, CO, USA

    Angelo D'Alessandro

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Zarini, S., Barkley, R.M., Gijón, M.A., Murphy, R.C. (2019). Overview of Lipid Mass Spectrometry and Lipidomics. In: D'Alessandro, A. (eds) High-Throughput Metabolomics. Methods in Molecular Biology, vol 1978. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9236-2_6

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  • DOI: https://doi.org/10.1007/978-1-4939-9236-2_6

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9235-5

  • Online ISBN: 978-1-4939-9236-2

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