Lipidomics pp 391-411 | Cite as

Membrane Lipidomics and the Geometry of Unsaturated Fatty Acids From Biomimetic Models to Biological Consequences

  • Carla Ferreri
  • Chryssostomos Chatgilialoglu
Part of the Methods in Molecular Biology book series (MIMB, volume 579)


In the last decades, free radical processes delineated an interdisciplinary field linking chemistry to biology and medicine. Free radical mechanisms became of importance as molecular basis of physiological and pathological conditions. Lipids, in particular, unsaturated fatty acids, are susceptible of free radical attack. The reactivity of the double bond toward free radicals is well known, in particular the reversible addition of radical species to this functionality determines the cistrans double bond isomerization. Since the prevalent geometry displayed by unsaturated fatty acids in eukaryotes is cis, the occurrence of the cistrans isomerization by free radicals corresponds to the loss of an important structural information linked to biological activity. The formation of trans isomers can have important meaning and consequences connected to radical stress.

Free radical isomerization of membrane fatty acids has been the subject of research coupling the top-down approach by model studies, such as biomimetic chemistry in liposomes, with the bottom-up approach dealing with the examination of cell membrane lipidome in living systems under several physiopathological conditions. Methodologies and molecular libraries have been settled, for both liposome experiments and the examination of the radical stress in biological membranes. This chapter will give an overview of the current procedures used for liposome models and the cistrans isomerization experiments, in order to build-up a library of trans geometrical fatty acid isomers.

Key words

Membrane lipidomics Geometrical trans fatty acid Radical stress Liposome Biomimetic chemistry Free radical isomerization 



The authors wish to thank all collaborators that helped to develop methodologies in an interdisciplinary context. Support and sponsorship of the COST Action CM0603 “Free Radicals in Chemical Biology” is gratefully acknowledged.


  1. 1.
    Watson AD. 2006. Lipidomics: a global approach to lipid analysis in biological systems, J Lipid Res 47:2101–2111.PubMedCrossRefGoogle Scholar
  2. 2.
    Wenk MR. 2005. The emerging field of lipidomics. Nat Rev Drug Discov 4:594–610.PubMedCrossRefGoogle Scholar
  3. 3.
    Ferreri C, Chatgilialoglu C. 2005. Geometrical trans lipid isomers: a new target for lipidomics. ChemBioChem 6:1722–1734.PubMedCrossRefGoogle Scholar
  4. 4.
    Chatgilialoglu C, Ferreri C. 2005. Trans lipids: the free radical path. Chem Rev 31:441–448.Google Scholar
  5. 5.
    Ferreri C, Panagiotaki M, Chatgilialoglu C. 2007. Trans fatty acids in membranes: the free radical path. Mol Biotechnol 37:19–25.PubMedCrossRefGoogle Scholar
  6. 6.
    Dugave C, Demange L. 2003. Cis–trans isomerization of organic molecules and biomolecules: implications and applications. Chem Rev 103:2475–2532.PubMedCrossRefGoogle Scholar
  7. 7.
    Vance DE, Vance JE, eds. 2002. Biochemistry of lipids, lipoproteins and membranes, 4th ed., Elsevier: Amsterdam.Google Scholar
  8. 8.
    Sébédio JL, Christie WW, eds. 1998. Trans fatty acids in human nutrition. The Oily Press: Dundee.Google Scholar
  9. 9.
    Chatgilialoglu C. 2007. Fats of life… explaining the villainous properties of trans fatty acids. Optimum Nutr 40–43.Google Scholar
  10. 10.
    Larquè E, Zamora S, Gil A. 2001. Dietary trans fatty acids in early life: a review. Early Human Develop. 65:S31–S41.CrossRefGoogle Scholar
  11. 11.
    Hu FB, Stampfer MJ, Manson JE, Rimm E, Colditz GA, Rosner BA, Hennekens CH, Willett WC. 1997. Dietary fat intake and the risk of coronary artery disease in women. N Engl J Med 337:1491–1499.PubMedCrossRefGoogle Scholar
  12. 12.
    Koletzko B, Decsi T. 1997. Metabolic aspects of trans fatty acids. Clin Nutr 16:229–237.PubMedCrossRefGoogle Scholar
  13. 13.
    Sébédio JL, Vermunt SHF, Chardigny JM, Beaufrére B, Mensink RP, Armstrong RA, Christie WW, Niemela J, Hènon G, Riemersma RA. 2005. The effect of dietary α-linolenic acid on plasma lipids and platelet fatty acid composition: the transLinE study. Eur J Clin Nutr 54:104–113.CrossRefGoogle Scholar
  14. 14.
    Bender Brandt M, LeGault LA. 2003. What’s new on nutrition labelling at the United States Food and Drug Administration? J Food Comp Anal 16:383–393.CrossRefGoogle Scholar
  15. 15.
    Dieffenbacher A, Dysseler P. 1997. The determination of trans unsaturated fatty acids in edible oils and fats by capillary gas–liquid chromarography. Pure Appl Chem 69:1829–1837.CrossRefGoogle Scholar
  16. 16.
    Firestone D ed. 1998. Official Methods and Recommended Practices, Recommended Practice Cd 14d-96, 5th ed, American Oil Chemists’ Society: Champaign.Google Scholar
  17. 17.
    Samadi A, Andreu I, Ferreri C, Dellonte S, Chatgilialoglu C. 2004. Thiyl radical–catalysed isomerization of oils: an entry to the trans lipid library. J Am Oil Chem Soc 81:753–758.CrossRefGoogle Scholar
  18. 18.
    Mjøs SA. 2005. Properties of trans isomers of eicosapentaenoic acid and docosahexaenoic acid methyl esters on cyanopropyl stationary phases. J Chromat A 1100:185–192.CrossRefGoogle Scholar
  19. 19.
    Ji H, Voinov VG, Deinzer ML, Barofsky DF. 2007. Distinguishing between cis/trans isomers of monounsaturated fatty Acids by FAB MS. Anal Chem 79:1519–1522.PubMedCrossRefGoogle Scholar
  20. 20.
    Williams CM, Mander LN. 2001. Chromatography with silver nitrate. Tetrahedron 57:425–477.CrossRefGoogle Scholar
  21. 21.
    Lock AL, Corl BA, Barbano DM, Bauman DE, Ip C. 2004. The anticarcinogenic effect of trans-11 18:1 is dependent on its conversion to cis-9, trans-11 CLA by delta9-desaturase in rats. J Nutr 134:2698–2704.PubMedGoogle Scholar
  22. 22.
    Ferreri C, Kratzsch S, Brede O, Marciniak B, Chatgilialoglu C. 2005. Trans lipid formation induced by thiols in human monocytic leukemia cells. Free Radical Biol Med 38:1180–1187.CrossRefGoogle Scholar
  23. 23.
    Cevc G, ed. 1993. Phospholipid Handbook, Marcel Dekker: New York.Google Scholar
  24. 24.
    New RRC. 1990. Liposomes: A Practical Approach. IRL Press: Oxford.Google Scholar
  25. 25.
    Lasic DD. 1993. Liposomes. From Physics to Applications. Elsevier: Amsterdam.Google Scholar
  26. 26.
    Ferreri C, Manco I, Faraone-Mennella MR, Torreggiani A, Tamba M, Manara S, Chatgilialoglu C. 2006. The reaction of hydrogen atoms with methionine residues: a model of reductive radical stress causing tandem protein–lipid damage. ChemBioChem 7:1738–1744.PubMedCrossRefGoogle Scholar
  27. 27.
    Mozziconacci O, Bobrowski K, Ferreri C, Chatgilialoglu C. 2007. Reaction of hydrogen atom with Met-enkephalin and related peptides. Chem Eur J 13:2029–2033PubMedCrossRefGoogle Scholar
  28. 28.
    Niki E, Kawakami A, Yamamoto Y, Kamiya Y. 1985. Synergistic inhibition of oxidation of soybean phosphatidycholine liposomes in aqueous dispersion by vitamin E and vitamin C. Bull Chem Soc Jpn 58:1971–1975.CrossRefGoogle Scholar
  29. 29.
    Jacob RF, Mason RP. 2005. Lipid peroxidation induces cholesterol domain formation in model membranes. J Biol Chem 280:39380–39387.PubMedGoogle Scholar
  30. 30.
    MacDonald RC, MacDonald RI, Menco BP, Takeshita K, Subbarao NK, Hu LR. 1991. Small-volume extrusion apparatus for preparation of large, unilamellar vesicles. Biochim Biophys Acta 1061:297–303.PubMedGoogle Scholar
  31. 31.
    Batzri S, Korn ED. 1973. Single bilayer liposomes prepared without sonication. Biochim Biophys Acta 298:1015–1019.PubMedCrossRefGoogle Scholar
  32. 32.
    Domazou AS, Luisi PL. 2002. Size distribution of spontaneously formed liposomes by the alcohol injection method. J Liposome Res 12:205–220.PubMedCrossRefGoogle Scholar
  33. 33.
    Hanlon MC, Seybert DW. 1997. The pH dependence of lipid peroxidation using water-soluble azoinitiators. Free Radical Biol Med 23:712–719.CrossRefGoogle Scholar
  34. 34.
    von Sonntag C. 1987. The Chemical Basis of Radiation Biology. Taylor & Francis: New York.Google Scholar
  35. 35.
    Alfassi ZB. 1999. S-Centered Radicals. Wiley: Chichester.Google Scholar
  36. 36.
    Ferreri C, Pierotti S, Barbieri A, Zambonin L, Landi L, Rasi S, Luisi PL, Barigelletti F, Chatgilialoglu C. 2006. Comparison of phosphatidylcholine vesicle properties related to geometrical isomerism. Photochem Photobiol 82:274–280.PubMedCrossRefGoogle Scholar
  37. 37.
    Ferreri C, Samadi A, Sassatelli F, Landi L, Chatgilialoglu C. 2004. Regioselective cis-trans isomerization of arachidonic double bonds by thiyl radicals: the influence of phospholipid supramolecular organization. J Am Chem Soc 126:1063–1072.PubMedCrossRefGoogle Scholar
  38. 38.
    Ihara H, Hashizuma N, Hemmi H, Yoshida M. 2000. Antioxidant ability of bilirubin, vitamin E, vitamin C and albumin in the peroxyl-radical-induced hemolysis of human erythrocytes. J Anal Biosci 23:425–430.Google Scholar
  39. 39.
    Ferreri C, Chatgilialoglu C, Torreggiani A, Salzano AM, Renzone G, Scaloni A. 2008. The reductive desulfurization of Met and Cys residues in bovine RNase A is associated with trans lipids formation in a mimetic model of biological membranes. J Prot Res 7:2007–2015.CrossRefGoogle Scholar
  40. 40.
    Kadlcik V, Sicard-Roselli C, Houée-Levin C, Ferreri C, Chatgilialoglu C. 2006. Reductive modification of methionine residue in amyloid β-peptide. Angew Chem Int Ed 45:2595–2598.CrossRefGoogle Scholar
  41. 41.
    Ferreri C, Faraone Mennella MR, Formisano C, Landi L, Chatgilialoglu C. 2002. Arachidonate geometrical isomers generated by thiyl radicals: the relationship with trans lipids detected in biological samples. Free Radical Biol Med 33:1516–1526.CrossRefGoogle Scholar
  42. 42.
    Ferreri C, Angelini F, Chatgilialoglu C, Dellonte S, Moschese V, Rossi P, Chini L. 2005. Trans fatty acids and atopic eczema/dermatitis syndrome: the relationship with a free radical cis.trans isomerization of membrane lipids. Lipids 40:661–667.PubMedCrossRefGoogle Scholar
  43. 43.
    Puca AA, Novelli V, Viviani C, Andrew P, Somalvico F, Cirillo NA, Chatgilialoglu C, Ferreri C. 2008. Lipid profile of erythrocyte membranes as possible biomarker of longevity. Rejuven Res 11:63–72.CrossRefGoogle Scholar
  44. 44.
    Wilson R, Sargent JR. 2001. Chain separation of monounsaturated fatty acid methyl esters by argentation thin-layer chromatography. J Chromat A 905:251–257.CrossRefGoogle Scholar
  45. 45.
    Dobson G, Christie WW, Nikolova-Damyanova B. 1995. Silver ion chromatography of lipids and fatty acids. J Chromat B 671:197–222.CrossRefGoogle Scholar
  46. 46.
    Morris LJ. 1966. Separation of lipids by silver ion chromatography. J Lipid Res 7:717–732.PubMedGoogle Scholar
  47. 47.
    Rouser G, Fkeischer S, Yamamoto A. 1970. Two dimensional thin layer chromatographic separation of polar lipids and determination phospholipids by phosphorus analysis of spots. Lipids 5: 494–496.PubMedCrossRefGoogle Scholar
  48. 48.
    Griffiths WJ. 2003. Tandem mass spectrometry in the study of fatty acids, bile acids, and steroids. Mass Spectrom Rev 22:81–152.PubMedCrossRefGoogle Scholar
  49. 49.
    Han X, Gross RW. 2003. Global analysis of cellular lipidomes directly from crude extracts of biological samples by ESI mass spectrometry. A bridge to lipidomics. J Lipid Res 44:1071–1079.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Carla Ferreri
    • 1
  • Chryssostomos Chatgilialoglu
    • 2
  1. 1.ISOF-BioFree Radicals, Consiglio Nazionale delle RicericheBolognaItaly
  2. 2.ISOF, Consiglio Nazionale delle RicercheBolognaItaly

Personalised recommendations