Caitlin E Randolph1, Stephen J Blanksby2, Scott A McLuckey1. 1. Department of Chemistry , Purdue University , West Lafayette , Indiana 47907-2084 , United States. 2. Central Analytical Research Facility, Institute for Future Environments , Queensland University of Technology , Brisbane , QLD 4000 , Australia.
Abstract
Shotgun lipidomics has recently gained popularity for lipid analysis. Conventionally, shotgun analysis of glycerophospholipids via direct electrospray ionization tandem mass spectrometry (ESI-MS/MS) provides glycerophospholipid (GPL) class (i.e., headgroup composition) and fatty acyl composition. Reliant on low-energy collision-induced dissociation (CID), traditional ESI-MS/MS fails to define fatty acyl regiochemistry along the glycerol backbone or carbon-carbon double bond position(s) in unsaturated fatty acyl substituents. Therefore, isomeric GPLs are often unresolved, representing a significant challenge for shotgun-MS approaches. We developed a top-down shotgun-MS method utilizing gas-phase ion/ion charge inversion chemistry that provides near-complete GPL structural identification. First, in negative ion mode, CID of mass-selected GPL anions generates fatty acyl carboxylate anions via fragmentation of ester bonds linking the fatty acyl substituents at the sn-1 and sn-2 positions of the glycerol backbone. Product anions, including fatty acyl carboxylate ions, were then derivatized in the mass spectrometer via an ion/ion charge inversion reaction with tris-phenanthroline magnesium dications. Subsequent CID of charge-inverted fatty acyl complex cations yielded isomer-specific product ion spectra that permit (i) unambiguous assignment of carbon-carbon double bond position(s) and (ii) relative quantitation of isomeric fatty acyl substituents. The outlined strategy was applied to the analysis of targeted GPLs extracted from human plasma, including several proposed plasma biomarkers. A single experiment thus facilitates assignment of the GPL headgroup, fatty acyl composition, carbon-carbon double bond position(s) in unsaturated fatty acyl chains, and, in some cases, fatty acyl sn-position and relative abundances for isomeric fatty acyl substituents. Ultimately, this MSn platform paired with ion/ion chemistry permitted identification of major, and some minor, isomeric contributors that are unresolved using conventional ESI-MS/MS.
Shotgun lipidomics has recently gained popularity for pan class="Chemical">lipid analysis. Conventionally, shotgun analysis of glycerophospholipids via direct electrospray ionization tandem mass spectrometry (ESI-MS/MS) provides glycerophospholipid (GPL) class (i.e., headgroup composition) and fatty acyl composition. Reliant on low-energy collision-induced dissociation (CID), traditional ESI-MS/MS fails to define fatty acyl regiochemistry along the glycerol backbone or carbon-carbon double bond position(s) in unsaturated fatty acyl substituents. Therefore, isomeric GPLs are often unresolved, representing a significant challenge for shotgun-MS approaches. We developed a top-down shotgun-MS method utilizing gas-phase ion/ion charge inversion chemistry that provides near-complete GPL structural identification. First, in negative ion mode, CID of mass-selected GPLanions generates fatty acyl carboxylateanions via fragmentation of ester bonds linking the fatty acyl substituents at the sn-1 and sn-2 positions of the glycerol backbone. Product anions, including fatty acyl carboxylate ions, were then derivatized in the mass spectrometer via an ion/ion charge inversion reaction with tris-phenanthroline magnesium dications. Subsequent CID of charge-inverted fatty acyl complex cations yielded isomer-specific product ion spectra that permit (i) unambiguous assignment of carbon-carbon double bond position(s) and (ii) relative quantitation of isomeric fatty acyl substituents. The outlined strategy was applied to the analysis of targeted GPLs extracted from human plasma, including several proposed plasma biomarkers. A single experiment thus facilitates assignment of the GPL headgroup, fatty acyl composition, carbon-carbon double bond position(s) in unsaturated fatty acyl chains, and, in some cases, fatty acylsn-position and relative abundances for isomeric fatty acyl substituents. Ultimately, this MSn platform paired with ion/ion chemistry permitted identification of major, and some minor, isomeric contributors that are unresolved using conventional ESI-MS/MS.
Authors: Cristina Razquin; Estefanía Toledo; Clary B Clish; Miguel Ruiz-Canela; Courtney Dennis; Dolores Corella; Christopher Papandreou; Emilio Ros; Ramon Estruch; Marta Guasch-Ferré; Enrique Gómez-Gracia; Montserrat Fitó; Edward Yu; José Lapetra; Dong Wang; Dora Romaguera; Liming Liang; Angel Alonso-Gómez; Amy Deik; Mónica Bullo; Lluis Serra-Majem; Jordi Salas-Salvadó; Frank B Hu; Miguel A Martínez-González Journal: Diabetes Care Date: 2018-10-16 Impact factor: 19.112
Authors: Hector Martinez-Seara; Tomasz Róg; Marta Pasenkiewicz-Gierula; Ilpo Vattulainen; Mikko Karttunen; Ramon Reigada Journal: J Phys Chem B Date: 2007-08-31 Impact factor: 2.991
Authors: Piyushkumar A Mundra; Christopher K Barlow; Paul J Nestel; Elizabeth H Barnes; Adrienne Kirby; Peter Thompson; David R Sullivan; Zahir H Alshehry; Natalie A Mellett; Kevin Huynh; Kaushala S Jayawardana; Corey Giles; Malcolm J McConville; Sophia Zoungas; Graham S Hillis; John Chalmers; Mark Woodward; Gerard Wong; Bronwyn A Kingwell; John Simes; Andrew M Tonkin; Peter J Meikle Journal: JCI Insight Date: 2018-09-06
Authors: John A Bowden; Alan Heckert; Candice Z Ulmer; Christina M Jones; Jeremy P Koelmel; Laila Abdullah; Linda Ahonen; Yazen Alnouti; Aaron M Armando; John M Asara; Takeshi Bamba; John R Barr; Jonas Bergquist; Christoph H Borchers; Joost Brandsma; Susanne B Breitkopf; Tomas Cajka; Amaury Cazenave-Gassiot; Antonio Checa; Michelle A Cinel; Romain A Colas; Serge Cremers; Edward A Dennis; James E Evans; Alexander Fauland; Oliver Fiehn; Michael S Gardner; Timothy J Garrett; Katherine H Gotlinger; Jun Han; Yingying Huang; Aveline Huipeng Neo; Tuulia Hyötyläinen; Yoshihiro Izumi; Hongfeng Jiang; Houli Jiang; Jiang Jiang; Maureen Kachman; Reiko Kiyonami; Kristaps Klavins; Christian Klose; Harald C Köfeler; Johan Kolmert; Therese Koal; Grielof Koster; Zsuzsanna Kuklenyik; Irwin J Kurland; Michael Leadley; Karen Lin; Krishna Rao Maddipati; Danielle McDougall; Peter J Meikle; Natalie A Mellett; Cian Monnin; M Arthur Moseley; Renu Nandakumar; Matej Oresic; Rainey Patterson; David Peake; Jason S Pierce; Martin Post; Anthony D Postle; Rebecca Pugh; Yunping Qiu; Oswald Quehenberger; Parsram Ramrup; Jon Rees; Barbara Rembiesa; Denis Reynaud; Mary R Roth; Susanne Sales; Kai Schuhmann; Michal Laniado Schwartzman; Charles N Serhan; Andrej Shevchenko; Stephen E Somerville; Lisa St John-Williams; Michal A Surma; Hiroaki Takeda; Rhishikesh Thakare; J Will Thompson; Federico Torta; Alexander Triebl; Martin Trötzmüller; S J Kumari Ubhayasekera; Dajana Vuckovic; Jacquelyn M Weir; Ruth Welti; Markus R Wenk; Craig E Wheelock; Libin Yao; Min Yuan; Xueqing Heather Zhao; Senlin Zhou Journal: J Lipid Res Date: 2017-10-06 Impact factor: 5.922
Authors: Molly S Blevins; Virginia K James; Carmen M Herrera; Alexandria B Purcell; M Stephen Trent; Jennifer S Brodbelt Journal: Anal Chem Date: 2020-06-16 Impact factor: 6.986
Authors: Caitlin E Randolph; De'Shovon M Shenault; Stephen J Blanksby; Scott A McLuckey Journal: J Am Soc Mass Spectrom Date: 2020-04-14 Impact factor: 3.109
Authors: Caitlin E Randolph; De'Shovon M Shenault; Stephen J Blanksby; Scott A McLuckey Journal: J Am Soc Mass Spectrom Date: 2020-12-28 Impact factor: 3.109