A comprehensive classification system for lipids

Fahy, Eoin; Subramaniam, Shankar; Brown, H. Alex; Glass, Christopher K.; Merrill, Alfred H.; Murphy, Robert C.; Raetz, Christian R. H.; Russell, David W.; Seyama, Yousuke; Shaw, Walter A.; Shimizu, Takao; Spener, Friedrich; Meer, Gerrit van; VanNieuwenhze, Michael S.; White, Stephen H.; Witztum, Joseph L.; Dennis, Edward A.

doi:10.1194/jlr.e400004-jlr200

Cited by 1,432 publications

(742 citation statements)

References 39 publications

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“…Neither the Lipid Maps nomenclature 37, 38 nor widely accepted existing MS specific shorthand lipidomic nomenclature systems 39 currently include NAPEs. We therefore propose the following nomenclature based on 39, defining NAPE species as derived from N ‐acylation of the corresponding PE molecules: e.g.…”

Section: Resultsmentioning

confidence: 99%

Quantitative analysis of N‐acylphosphatidylethanolamine molecular species in rat brain using solid‐phase extraction combined with reversed‐phase chromatography and tandem mass spectrometry

Triebl

Weissengruber

Trötzmüller

et al. 2016

J of Separation Science

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A novel method for the sensitive and selective identification and quantification of N‐acylphosphatidylethanolamine molecular species was developed. Samples were prepared using a combination of liquid–liquid and solid‐phase extraction, and intact N‐acylphosphatidylethanolamine species were determined by reversed‐phase high‐performance liquid chromatography coupled to positive electrospray tandem mass spectrometry. As a result of their biological functions as precursors for N‐acylethanolamines and as signaling molecules, tissue concentrations of N‐acylphosphatidylethanolamines are very low, and their analysis is additionally hindered by the vast excess of other sample components. Our sample preparation methods are able to selectively separate the analytes of interest from any expected biological interferences. Finally, the highest selectivity is achieved by coupling chromatographic separation and two N‐acyl chain specific selected reaction monitoring scans per analyte, enabling identification of both the N‐acyl chain and the phosphatidylethanolamine moiety. The validated method is suitable for the reliable quantification of N‐acylphosphatidylethanolamine species from rat brain with a lower limit of quantification of 10 pmol/g and a linear range up to 2300 pmol/g. In total, 41 N‐acylphosphatidylethanolamine molecular species with six different N‐acyl chains, amounting to a total concentration of 3 nmol/g, were quantified.

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Section: Resultsmentioning

confidence: 99%

Quantitative analysis of N‐acylphosphatidylethanolamine molecular species in rat brain using solid‐phase extraction combined with reversed‐phase chromatography and tandem mass spectrometry

Triebl

Weissengruber

Trötzmüller

et al. 2016

J of Separation Science

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“…We have compiled a comprehensive library of eicosanoid standards, which is available in the supplemental material. The library contains information on each standard listed in Table 2 that includes LC-RT, systematic nomenclature and LIPID MAPS ID number (20), and an MS/MS fragmentation spectrum. If other reversed-phase liquid chromatography conditions are employed, these retention times can still be useful, because the order of elution should not drastically change; e.g.…”

Section: Aa-dmentioning

confidence: 99%

Arachidonate-derived Dihomoprostaglandin Production Observed in Endotoxin-stimulated Macrophage-like Cells

Harkewicz

Fahy

Andreyev

et al. 2007

Journal of Biological Chemistry

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Eicosanoids, including the prostaglandins, leukotrienes, hydroxyeicosatetraenoic acids, epoxyeicosatetraenoic acids, and related compounds, are biosynthetic, bioactive mediators derived from arachidonic acid (AA), a 20:4(n-6) fatty acid. We have developed a comprehensive and sensitive mass spectral analysis to survey eicosanoid release from endotoxin-stimulated RAW 264.7 macrophage-like cells that is capable of detecting over 70 diverse eicosanoids and eicosanoid metabolites, should they be present. We now address the question: Are biologically significant eicosanoids being overlooked? Herein, we illustrate a general approach to diverse isotope metabolic profiling of labeled exogenous substrates using mass spectrometry (DIM-PLES/MS), demonstrated for one substrate (AA) and its resultant products (eicosanoids). RAW cells were incubated in medium supplemented with deuterium-labeled AA. When the cells are stimulated, two sets of eicosanoids are produced, one from endogenous AA and the other from the supplemented (exogenous) deuterium-labeled form. This produces a signature mass spectral "doublet" pattern, allowing for a comprehensive and diverse eicosanoid search requiring no previous knowledge or assumptions as to what these species may be, in contrast to traditional methods. We report herein observing unexpected AA metabolites generated by the cells, some of which may constitute novel bioactive eicosanoids or eicosanoid inactivation metabolites, as well as demonstrating differing metabolic pathways for the generation of isomeric prostaglandins and potential peroxisome proliferator-activated receptor activators. Unexpectedly, we report observing a series of 1a,1b-dihomologue prostaglandins, products of adrenic acid (22:4(n-6)), resulting from the two-carbon elongation of AA by the RAW cells.Starting in the early 1960s with the first structural characterization of the prostaglandins (1), mass spectrometry (MS) 2 has played a critical role in the biochemical study of eicosanoids. More recent advances in electrospray ionization-MS coupled to high-performance liquid chromatography have offered extremely sensitive and quantitative assays for most of the eicosanoids (2), without the need for chemical derivatization prior to analysis as was required by earlier gas chromatography electron ionization-MS methods (3). It is important to recognize, however, that while advances in high-performance LC-MS methods have offered extensive capabilities for surveying a number of different eicosanoid species in a single analysis, to date most efforts have focused on a specific eicosanoid or eicosanoid class, and additionally, with advanced knowledge and assumptions as to the identity of these species (4 -11). Recently, however, investigators have begun to explore the development of theoretical databases and algorithms based on virtual liquid chromatography-UV spectroscopy-tandem mass spectrometry (MS/MS) spectra and chromatograms for identifying potential lipid mediators without synthetic or authentic products as standards (12).System...

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“…Biological membranes contain thousands of different lipid species that can be broadly classified according to their backbone structure (1). Of these, sphingolipids (SL) 2 have become particularly prominent due to the discovery of their unexpected structural complexity and their intricate modes of cellular trafficking and metabolism (2)(3)(4).…”

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confidence: 99%

A Critical Role for Ceramide Synthase 2 in Liver Homeostasis

Pewzner-Jung

Park

Laviad

et al. 2010

Journal of Biological Chemistry

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Ceramide is an important lipid signaling molecule that plays critical roles in regulating cell behavior. Ceramide synthesis is surprisingly complex and is orchestrated by six mammalian ceramide synthases, each of which produces ceramides with restricted acyl chain lengths. We have generated a CerS2 null mouse and characterized the changes in the long chain base and sphingolipid composition of livers from these mice. Ceramide and downstream sphingolipids were devoid of very long (C22-C24) acyl chains, consistent with the substrate specificity of CerS2 toward acyl-CoAs. Unexpectedly, C16-ceramide levels were elevated, and as a result, total ceramide levels were unaltered; however, C16-ceramide synthesis in vitro was not increased. Levels of sphinganine were also significantly elevated, by up to 50-fold, reminiscent of the effect of the ceramide synthase inhibitor, fumonisin B1. With the exceptions of glucosylceramide synthase and neutral sphingomyelinase 2, none of the other enzymes tested in either the sphingolipid biosynthetic or degradative pathways were significantly changed. Total glycerophospholipid and cholesterol levels were unaltered, although there was a marked elevation in C18:1 and C18:2 fatty acids in phosphatidylethanolamine, concomitant with a reduction in C18:0 and C20:4 fatty acids. Finally, differences were observed in the biophysical properties of lipid extracts isolated from liver microsomes, with membranes from CerS2 null mice displaying higher membrane fluidity and showing morphological changes. Together, these results demonstrate novel modes of cross-talk and regulation between the various branches of lipid metabolic pathways upon inhibition of very long acyl chain ceramide synthesis.Biological membranes contain thousands of different lipid species that can be broadly classified according to their backbone structure (1). Of these, sphingolipids (SL) 2 have become particularly prominent due to the discovery of their unexpected structural complexity and their intricate modes of cellular trafficking and metabolism (2-4). Ceramides are perhaps the most well studied class of SLs, because of their essential roles in differentiation and in apoptosis (5-7). Ceramides can differ in both their long chain sphingoid base (8) and fatty acid composition (9). Over the past few years, a complex mode of regulation of ceramide synthesis has been described, with each of the six mammalian ceramide synthase (CerS) (formerly known as Lass (longevity assurance)) genes generating ceramides with specific acyl chain lengths (10). Thus, CerS1 uses mostly C18-CoA (11); CerS4 uses C18-and C20-CoAs (12); CerS5 and CerS6 use mostly C16-CoA (12, 13); and CerS3 uses very long chain acyl-CoAs (C26 and higher) (14). CerS2 can utilize a wider range of fatty acyl-CoAs but uses mainly C22 to C24. In addition, CerS2 displays complex modes of regulation and has genomic features characteristic of a "housekeeping" gene, although no other CerS genes display these characteristics (15).We have now generated a CerS2 null mouse and have ...

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A comprehensive classification system for lipids

Cited by 1,432 publications

References 39 publications

Quantitative analysis of N‐acylphosphatidylethanolamine molecular species in rat brain using solid‐phase extraction combined with reversed‐phase chromatography and tandem mass spectrometry

Quantitative analysis of N‐acylphosphatidylethanolamine molecular species in rat brain using solid‐phase extraction combined with reversed‐phase chromatography and tandem mass spectrometry

Arachidonate-derived Dihomoprostaglandin Production Observed in Endotoxin-stimulated Macrophage-like Cells

A Critical Role for Ceramide Synthase 2 in Liver Homeostasis

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