Illustration of differences in the expression of genes for early steps of sphingolipid metabolism using a KEGG-based microarray analysis tool (GenMapp v2.1) that has been modified to display this pathway more completely (www.sphingomap.org). The sphingolipid metabolites and genes (with the gene abbreviations shown in boxes, or enzyme names where gene names are ambiguous) are given for the condensation of serine and palmitoyl-CoA to form 3-ketosphinganine (3-ketoSa) by serine palmitoyltransferase, which is reduced to sphinganine (Sa), acylated to dihydroceramides, DHCer, by (DH)Cer synthases, and incorporated into more complex DH-sphingolipids (the 1-phosphate, DHCerP, sphingomyelins, DHSM, glucosylceramides, DHGlcCer, galactosylceramides, DHGalCer, lactosylceramides, DHLacCer, and sulfatides, or desaturated to Cer followed by headgroup addition. Also included are a number of the catabolic genes, e.g., sphingomyelinases, SMases, ceramidases, ASAH, sphingosine kinases, for the formation of sphinganine 1-phosphate (Sa1P) and sphingosine 1-phosphate (So1P), and phosphatases for the reverse reaction and the lyase that cleaves sphingoid base 1-phosphates to ethanolamine phosphate (EP), hexadecanal (C16:0al) and hexadecenal (C16:1al). For the purpose of illustration, the coloration is for the log₂-fold difference in expression of these genes from a published microarray study (30) invasive lobular carcinoma cells versus normal lobular cells.

Display of the relative amounts of sphingolipids for early steps of sphingolipid metabolism and backbone turnover in a pathway related, nodal, context. This depiction is obtained by toggling from Fig. 2 in SphingoVisGrid (www.sphingomap.org) and shows the same data set comparison (sphingolipids from MCF7 cells with versus without treatment with fenretinide). Beginning at the lower left corner is the initial condensation of palmitoyl-CoA with serine (or alanine or glycine for formation of 1-deoxy- and 1-desoxymethyl-Sa, respectively) and proceeding to the right are the formation of 3-ketosphinganine (3KSa), sphinganine (Sa) and downstream metabolites: (DH)Cer, (DH)SM, etc. The lines that radiate from the sphingoid base nodes reflect the different amide-linked fatty acids (shown by acyl chain length and number of double bonds). Also shown are the additional derivatives of sphingoid bases, the 1-phosphates (Sa1P and S1P) and N-methyl-metabolites (N-Me_nSa, etc.). Only a few of the nodes have been labeled because the rest fit the same pattern.

Display of the relative amounts of sphingolipids for early steps of sphingolipid metabolism and backbone turnover. This depicts the relative amounts of sphingolipids in MCF7 breast cancer cells treated with 10 μM fenretinide (4HPR) for 24 h versus the control cells minus the drug using the SphingoVisGrid tool (www.sphingomap.org). The pathway layout in the upper panel is similar to the gene display in Fig. 1 wherein all of the N-acyl-chain lengths of the complex sphingolipids are summed in one box. It also includes the additional metabolites (from upper left): 1-deoxysphinganine (1-deoxySa) and related species (such as N-acyl-1-deoxysphinganine); N-acyl-3-ketosphinganine (N-acyl3KetoSa); N-methyl (mono-, di- and tri-) derivatives of the sphingoid bases (N-MeSo, etc.); and gangliosides GM1, GM2, and GM3 with distinction of Cer and DHCer backbones. The lower box distinguishes the complex sphingolipids by the specific sphingoid base backbone and the chain length and number of double bonds of the N-acyl-fatty acid (e.g., C16 = palmitic acid, C24:1 = nervonic acid, etc.). The coloring of each subspecies reflects the fold difference (log₂ as shown by the scale) for 4HPR-treated cells versus the control; gray boxes are for analytes that were not measured in this experiment.