Identification of double bond position in lipids: From GC to OzID

Mitchell, Todd W.; Pham, Hieu T.; Thomas, Michael C.; Blanksby, Stephen J.

doi:10.1016/j.jchromb.2009.01.017

Cited by 129 publications

(138 citation statements)

References 107 publications

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“…For example, negative mode fragmentation of PCs provides information on the chain length and number of double bonds present in each acyl chain, but does not provide empirical evidence on either the position of those acyl chains on the glycerol backbone or the position of the double bonds within the acyl chain. While mass spectrometry-based experiments have been developed to obtain further structural information on both these points ( 28 ), in the current context it is impractical to attempt to fully elucidate the composition of isomeric lipids. Due to the necessity for high throughput in the context of population profi ling, only limited structural elucidation is achieved, as refl ected in the nomenclature.…”

Section: Associations Of Lipids With Anthropometric and Physiologicalmentioning

confidence: 99%

Plasma lipid profiling in a large population-based cohort

Weir

Wong

Barlow

et al. 2013

Journal of Lipid Research

326

292

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This article is available online at http://www.jlr.org Circulating lipids, their biosynthesis, metabolism, and biological functions are intimately involved in many complex disease processes ( 1 ). Traditional clinical chemistry uses measurements of total cholesterol, triglycerides, and HDL as tools for determining health status and disease risk. The tests for these lipids are low cost, high throughput, and well established. The development of soft ionization techniques, particularly electrospray ionization has proven to be a watershed for lipidomics, allowing the detection and quantifi cation of individual molecular species. Recently, the Lipid Maps Consortium described a detailed analysis of the plasma lipidome, reporting on the concentration of nearly 600 lipids in pooled human plasma from healthy individuals ( 1, 2 ). This analysis highlighted the complexity of the plasma lipidome and the potential of plasma lipid profi ling for disease classifi cation, risk assessment, and to uncover changes in lipid metabolism associated with disease states. To date, plasma lipid profi ling has been used to identify lipidomic biomarkers associated with a variety of diseases and activities related to obesity ( 3 ), hypertension ( 4 ), smoking ( 5 ), cystic fi brosis ( 6 ), weight loss ( 7 ), and type 2 diabetes ( 8 ). These studies have, in general, have been conducted using relatively small cohorts (<100 participants) ( 3, 4, 6, 7 ) and/or limited coverage of the lipidome (<100 species) ( 4, 6, 8 ).Abstract We have performed plasma lipid profi ling using liquid chromatography electrospray ionization tandem mass spectrometry on a population cohort of more than 1,000 individuals. From 10 l of plasma we were able to acquire comparative measures of 312 lipids across 23 lipid classes and subclasses including sphingolipids, phospholipids, glycerolipids, and cholesterol esters (CEs) in 20 min. Using linear and logistic regression, we identifi ed statistically signifi cant associations of lipid classes, subclasses, and individual lipid species with anthropometric and physiological measures. In addition to the expected associations of CEs and triacylglycerol with age, sex, and body mass index (BMI), ceramide was signifi cantly higher in males and was independently associated with age and BMI. Associations were also observed for sphingomyelin with age but this lipid subclass was lower in males. Lysophospholipids were associated with age and higher in males, but showed a strong negative association with BMI. Many of these lipids have previously been associated with chronic diseases including cardiovascular disease and may mediate the interactions of age, sex, and obesity with disease risk. -Weir, J. M., G.

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Section: Associations Of Lipids With Anthropometric and Physiologicalmentioning

confidence: 99%

Plasma lipid profiling in a large population-based cohort

Weir

Wong

Barlow

et al. 2013

Journal of Lipid Research

326

292

View full text Add to dashboard Cite

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“…Identifying the position of carbon-carbon double bond(s) in unsaturated lipids has challenged analysts for over 50 years, and this history has recently been reviewed [21]. In the context of lipid-protein interactions, methods for on-line analysis within the mass spectrometer itself are ideal as they harness the sensitivity of the mass spectrometer and even its mass-selection capabilities for lipid "purification."…”

Section: Locating Carbon-carbon Double Bondsmentioning

confidence: 99%

Time to Face the Fats: What Can Mass Spectrometry Reveal about the Structure of Lipids and Their Interactions with Proteins?

Brown

Mitchell

Oakley

et al. 2012

J. Am. Soc. Mass Spectrom.

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Since the 1950s, X-ray crystallography has been the mainstay of structural biology, providing detailed atomic-level structures that continue to revolutionize our understanding of protein function. From recent advances in this discipline, a picture has emerged of intimate and specific interactions between lipids and proteins that has driven renewed interest in the structure of lipids themselves and raised intriguing questions as to the specificity and stoichiometry in lipid-protein complexes. Herein we demonstrate some of the limitations of crystallography in resolving critical structural features of ligated lipids and thus determining how these motifs impact protein binding. As a consequence, mass spectrometry must play an important and complementary role in unraveling the complexities of lipid-protein interactions. We evaluate recent advances and highlight ongoing challenges towards the twin goals of (1) complete structure elucidation of low, abundant, and structurally diverse lipids by mass spectrometry alone, and (2) assignment of stoichiometry and specificity of lipid interactions within protein complexes.Key words: Lipid-protein interactions, Structural biology, Structural lipidomics, Protein mass spectrometry Lipid-Protein Interactions P roteins and lipids, both integral for the function of all biological systems, are chemically distinct. A protein's three-dimensional structure and ultimately its function are defined by peptide-bonded amino acids and subsequent posttranslational modifications. In contrast, lipids are smaller molecules than proteins, but have a larger array of building blocks and linkage chemistries. Because of these inherent chemical differences, the optimal tools for de novo structural characterization differ between proteins and lipids.Lipid-protein interactions are critical for maintaining biological function in the membrane bilayer, the cytosol, and extracellular space. In the membrane, the chemical structures of lipid solvent molecules are important for the correct folding, insertion, structure, and function of membrane proteins. The interactions between enzymes and their respective lipid substrates are critical for correct substrate recognition and catalysis (e.g., lipoxygenase [1]). Additionally, lipid-protein interactions are increasingly being realized as important in maintaining cellular structure (e.g., cytoskeletal anchoring [2]), scaffolding and localization of multi-subunit protein complexes (e.g., associated kinase anchoring protein complexes [3]), and as second messengers in signal transduction (e.g., protein kinase C [4]).

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“…Indeed, the difference in geometrical and positional arrangements of the conjugated double-bond system has been implicated in the preferential oxidation of 18:2(10E,12Z) in mitochondria, leading to preferential tissue accumulation of the 18:2(9Z,11E) isomer [19,20]. Such observations are part of a broader picture, where seemingly minor disturbances in lipids at the molecular level (for instance, double-bond location) are associated with changes in metabolism and disease [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Ozone-Induced Dissociation of Conjugated Lipids Reveals Significant Reaction Rate Enhancements and Characteristic Odd-Electron Product Ions

Maccarone

Campbell²,

Mitchell

et al. 2013

J. Am. Soc. Mass Spectrom.

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. Ozone-induced dissociation of conjugated lipids reveals significant reaction rate enhancements and characteristic odd-electron product ions. Journal of the American Society for Mass Spectrometry, 24 (2), 286-296.Ozone-induced dissociation of conjugated lipids reveals significant reaction rate enhancements and characteristic odd-electron product ions AbstractOzone-induced dissociation (OzID) is an alternative ion activation method that relies on the gas phase ionmolecule reaction between a mass-selected target ion and ozone in an ion trap mass spectrometer. Herein, we evaluated the performance of OzID for both the structural elucidation and selective detection of conjugated carbon-carbon double bond motifs within lipids. The relative reactivity trends for [M + X]+ ions (where X = Li, Na, K) formed via electrospray ionization (ESI) of conjugated versus nonconjugated fatty acid methyl esters (FAMEs) were examined using two different OzID-enabled linear ion-trap mass spectrometers. Compared with nonconjugated analogues, FAMEs derived from conjugated linoleic acids were found to react up to 200 times faster and to yield characteristic radical cations. The significantly enhanced reactivity of conjugated isomers means that OzID product ions can be observed without invoking a reaction delay in the experimental sequence (i.e., trapping of ions in the presence of ozone is not required). This possibility has been exploited to undertake neutral-loss scans on a triple quadrupole mass spectrometer targeting characteristic OzID transitions. Such analyses reveal the presence of conjugated double bonds in lipids extracted from selected foodstuffs. Finally, by benchmarking of the absolute ozone concentration inside the ion trap, second order rate constants for the gas phase reactions between unsaturated organic ions and ozone were obtained. These results demonstrate a significant influence of the adducting metal on reaction rate constants in the fashion Li > Na > K. second order rate constants for the gas phase reactions between unsaturated organic ions and ozone were obtained. These results demonstrate a significant influence of the adducting metal on reaction rate constants in the fashion Li > Na > K.3

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Identification of double bond position in lipids: From GC to OzID

Cited by 129 publications

References 107 publications

Plasma lipid profiling in a large population-based cohort

Plasma lipid profiling in a large population-based cohort

Time to Face the Fats: What Can Mass Spectrometry Reveal about the Structure of Lipids and Their Interactions with Proteins?

Ozone-Induced Dissociation of Conjugated Lipids Reveals Significant Reaction Rate Enhancements and Characteristic Odd-Electron Product Ions

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