On the future of “omics”: lipidomics
- 735 Downloads
Following in the wake of the genomic and proteomic revolutions new fields of “omics” research are emerging. The metabolome provides the natural complement to the genome and proteome, however, the extreme physicochemical diversity of the metabolome leads to a subdivision of metabolites into compounds soluble in aqueous solutions or those soluble in organic solvents. A complete molecular and quantitative investigation of the latter when isolated from tissue, fluid or cells constitutes lipidomics. Like proteomics, lipidomics is a subject which is both technology driven and technology driving, with the primary technologies being mass spectrometry, with or without on-line chromatography and computer-assisted data analysis. In this paper we will examine the underlying fundamentals of different lipidomic experimental approaches including the “shotgun” and “top-down” global approaches, and the more targeted liquid chromatography – or gas chromatography – mass spectrometry approaches. Application of these approaches to the identification of in-born errors of metabolism will be discussed.
KeywordsBile Acid Desmosterol Fatty Acid Substituent Exact Mass Measurement Bile Acid Biosynthesis
This work was supported by funding from The Royal Society, BBSRC and EPSRC.
- Andreyev AY, Fahy E, Guan Z, Kelly S, Li X, McDonald JG, Milne S, Myers D, Park H, Ryan A, Thompson BM, Wang E, Zhao Y, Brown HA, Merrill AH, Raetz CR, Russell DW, Subramaniam S, Dennis EA (2010) Subcellular organelle lipidomics in TLR-4-activated macrophages. J Lipid Res 51:2785–2797PubMedCrossRefGoogle Scholar
- Björkhem I, Andersson U, Ellis E, Alvelius G, Ellegard L, Diczfalusy U, Sjövall J, Einarsson C (2001) From brain to bile. Evidence that conjugation and omega-hydroxylation are important for elimination of 24 S-hydroxycholesterol (cerebrosterol) in humans. J Biol Chem 276:37004–37010PubMedCrossRefGoogle Scholar
- Brown M, Dunn WB, Dobson P, Patel Y, Winder CL, Francis-McIntyre S, Begley P, Carroll K, Broadhurst D, Tseng A, Swainston N, Spasic I, Goodacre R, Kell DB (2009) Mass spectrometry tools and metabolite-specific databases for molecular identification in metabolomics. Analyst 134:1322–1332PubMedCrossRefGoogle Scholar
- Christie WW, Han X (2010) Lipid extraction, storage and sample handling. In: Lipid Analysis - Isolation, Separation, Identification and Lipidomic Analysis. The Oily Press, Bridgewater, England, pp 55–69Google Scholar
- Dennis EA, Brown AH, Deems RA, Glass CK, Merrill AH, Murphy RC, Raetz CR, Subramaniam S, Russell DW, vanNieuwenhze MS, White SH, Witztum JL, Wooley J (2005) The LIPID MAPS approach to lipidomics. In: Feng L, Prestwich G (eds) Functional Lipidomics. CRC Press/Taylor & Francis Group, Boca Raton, FL, pp 1–15CrossRefGoogle Scholar
- Goodwin B, Gauthier KC, Umetani M, Watson MA, Lochansky MI, Collins JL, Leitersdorf E, Mangelsdorf DJ, Kliewer SA, Repa JJ (2003) Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor. Proc Natl Acad Sci USA 100:223–228PubMedCrossRefGoogle Scholar
- Han X, Yang K, Gross RW (2008) Microfluidics-based electrospray ionization enhances the intrasource separation of lipid classes and extends identification of individual molecular species through multi-dimensional mass spectrometry: development of an automated high-throughput platform for shotgun lipidomics. Rapid Commun Mass Spectrom 22:2115–2124PubMedCrossRefGoogle Scholar
- 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 and Dennis EA (2010) Lipidomics reveals a remarkable diversity of lipids in human plasma. J. Lipid Res 51:3299–3305PubMedCrossRefGoogle Scholar
- Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B, Hau DD, Psychogios N, Dong E, Bouatra S, Mandal R, Sinelnikov I, Xia J, Jia L, Cruz JA, Lim E, Sobsey CA, Shrivastava S, Huang P, Liu P, Fang L, Peng J, Fradette R, Cheng D, Tzur D, Clements M, Lewis A, De SA, Zuniga A, Dawe M, Xiong Y, Clive D, Greiner R, Nazyrova A, Shaykhutdinov R, Li L, Vogel HJ, Forsythe I (2009) HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res 37:D603–D610PubMedCrossRefGoogle Scholar