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Journal of Lipid Research, Vol. 50, S97-S102, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Metabolism

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

Alfred H. Merrill, Jr.^1,*, Todd H. Stokes, Amin Momin^*, Hyejung Park^*, Brent J. Portz^*, Samuel Kelly^*, Elaine Wang^*, M. Cameron Sullards^* and May Dongmei Wang

^* Schools of Biology, Chemistry and Biochemistry and the Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332
Wallace H. Coulter Department of Biomedical Engineering and the Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332

This work was supported by the Lipid MAPS Consortium grant (GM069338) (A.H.M.) and in part by funds from Microsoft Research, the National Institutes of Health (Bioengineering Research Partnership R01CA108468, P20GM072069, the Center for Cancer Nanotechnology Excellence U54CA119338), and the Georgia Cancer Coalition (M.D.W.).

Published, JLR Papers in Press, November 21, 2008.

² With "higher" contingent on confirmation of the microarray results with a more quantitative method such as quantitative RT-PCR.

³ The labels shown in Figs. 2 and 3 have been added to the diagram to orient the reader; these are not shown on the original data display to make it easier for the viewer to see patterns.

⁴ SphingoVisGrid can display additional metabolites but these are colored grey when they have not been measured in a particular experiment.

¹ To whom correspondence should be addressed. e-mail: al.merrill{at}biology.gatech.edu

ABSTRACT

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-acyl-derivatives ("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.

Supplementary key words glycosphingolipids • ceramides • sphingoid bases • metabolism • lipidomics • systems biology

Abbreviations: 1-deoxySa, 1-deoxysphinganine; 3-ketoSa, 3-ketosphinganine; Cer, ceramides; Cerase, ceramidase; Cer1P, ceramide 1-phosphate; DHCer, dihydroceramide; EP, ethanolamine phosphate; ESI, electrospray ionization; GalCer, galactosylceramide; GlcCer, glucosylceramide; GM, ganglioside (GM1, GM2, GM3); KEGG, Kyoto Encyclopedia of Genes and Genomes; LacCer, lactosylceramide; MS/MS, tandem mass spectrometry; Sa, sphinganine; Sa1P, sphinganine 1-phosphate; So, sphingosine; So1P, sphingosine 1-phosphate; SM, sphingomyelin; SMase, sphingomyelinase; ST, sulfatide

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