Studies of lipid turnover in cells with stable isotope and gas chromatograph–mass spectrometry

Tserng, Kou‐Yi; Griffin, Ronda

doi:10.1016/j.ab.2003.10.037

Cited by 17 publications

(16 citation statements)

References 33 publications

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“…The components of the sample were repetitively monitored from m/z 200 to 800 at a rate of 1.27 scans/s [19]. The use of rep-etitive scan instead of selected ion monitoring of only a few selected ions of interest decreases the sensitivity of the analytic result.…”

Section: Gc-ms Measurement Of Ceramidesmentioning

confidence: 99%

Ceramide metabolite, not intact ceramide molecule, may be responsible for cellular toxicity

Tserng

Griffin

2004

Biochemical Journal

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Ceramides, which are produced from the hydrolysis of sphingomyelin or synthesized from serine and palmitate in a de novo pathway, are regarded as important cellular signals for inducing apoptosis. However, controversy over this proposed role of ceramides exists. Using stable isotope labelling coupled with GC (gas chromatography)-MS and mass isotopomer distribution analysis, we have studied the metabolism of exogenous long-chain ceramides in HL60 cells. Our results do not support the concept of enhanced ceramide transport into cells induced by solvent mixtures of ethanol and hydrocarbons. In addition, cell toxicity does not correlate with the amount of intact ceramide in the cells. Our results are more consistent with a disturbance of sphingomyelin metabolism induced by the solvent mixture. The characteristics of this disturbed sphingolipid disposition are the inhibition of dihydroceramide desaturation and an enhanced degradation of sphingomyelin. As a consequence, dihydroceramides accumulate and the cellular sphingomyelin content decreases. Inhibition of these pathways is most likely to be induced by the increased production of novel ceramide metabolites instead of by intact ceramides. Octadecane-1,2-diol is identified as a possible mediator. Treatments that divert ceramide degradation to the novel pathway are potential strategies in cancer therapy for inducing cell toxicity.

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Section: Gc-ms Measurement Of Ceramidesmentioning

confidence: 99%

Ceramide metabolite, not intact ceramide molecule, may be responsible for cellular toxicity

Tserng

Griffin

2004

Biochemical Journal

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“…Labeled data helps identify alternate/new pathways. 134 Further, it provides a more direct approach of computing fluxes and estimating the split ratios at branch points. Mass balance can be used to detect the leakage through unmodeled pathways and potential connections between two different parts of the pathway can be detected.…”

Section: Quantitative Kinetic Models Of Lipid Metabolismmentioning

confidence: 99%

“…Deconvoluting the spectra in the context of lipid metabolites to identify peaks has been discussed previously. 134a The main source of complexity in modeling labeled data is the presence of feedback loops. 135 When reactions result in elongation or breakdown of one or more chains of labeled carbon atoms or result in other structural changes then labeling of multiple carbon atoms changes even if all the carbon atoms in the original labeled metabolite were 13 C. These complexities need to be taken into account in using labeled data in kinetic modeling studies.…”

Section: Quantitative Kinetic Models Of Lipid Metabolismmentioning

confidence: 99%

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Bioinformatics and Systems Biology of the Lipidome

Subramaniam

Fahy²,

Gupta³

et al. 2011

Chem. Rev.

180

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“…Additional challenges for sphingolipidomic analysis include the need for information about metabolic flux, which could be approached using stable isotope precursors (17,18) and isotopomer analysis (19); and to know the location of these molecules, which is beginning to be addressed using bio-imaging MS. Bio-imaging MS (sometimes called Fig. 1.…”

Section: Sphingolipidomic Analysismentioning

confidence: 99%

Sphingolipidomics: a valuable tool for understanding the roles of sphingolipids in biology and disease

Merrill

Stokes

Momin

et al. 2009

Journal of Lipid Research

132

100

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The sphingolipidome is the portion of the lipidome that encompasses all sphingoid bases and their derivatives. Whereas the most studied sphingoid base is sphingosine [(2S,3R,4E)-2-aminooctadecene-1,3-diol], mammals have dozens of structural variants, and hundreds of additional types have been found in other eukaryotic organisms and some bacteria and viruses. Multiplying these figures by the N-acylderivatives ("ceramides") and the more than 500 phospho-and glyco-headgroups places the number of discrete molecular species in the tens of thousands or higher. Structure-specific, quantitative information about a growing fraction of the sphingolipidome can now be obtained using various types of chromatography coupled with tandem mass spectrometry, and application of these methods is producing many surprises regarding sphingolipid structure, metabolism, and function. Such large data sets can be difficult to interpret, but the development of tools that display results from genomic and lipidomic studies in a pathway relational, nodal, context can make it easier for investigators to deal with this complexity.

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Studies of lipid turnover in cells with stable isotope and gas chromatograph–mass spectrometry

Cited by 17 publications

References 33 publications

Ceramide metabolite, not intact ceramide molecule, may be responsible for cellular toxicity

Ceramide metabolite, not intact ceramide molecule, may be responsible for cellular toxicity

Bioinformatics and Systems Biology of the Lipidome

Sphingolipidomics: a valuable tool for understanding the roles of sphingolipids in biology and disease

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