1. Ceramide biosynthesisF G H I J K L M N O P Q R 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 N S E W 8 3 6 4 1 C
746
666
478
GP1c 80
371
217
299
335
GQ1c 77
GQ1b 78
GQ1bα 94
664
GQ1aα
290
749
336 2
GT1b 97 9
294
323
344
GQ1β
761
395
365
755
653
301
302
298
Gal-GD1b 92
756 76
GT1a 79
GT1c 74
GT1aα 90
752
754
751
Fuc-GD1b 93
348
293
404
343
342
269
204
339
349
334 91
GalNAc-
GD1a
308
GT1bα
324
402
305
304
328 85
341
312
482
GalNAc-GM1b 83
268
501
GD1c
130
338
774
775 75
773
GalNAc-GM1 86
345
307
780
GD1aα 88
779 96
GT2 71
303
782
KDN-GD1a
315
629
253
311
768
397
375
394
396
765
652
300
297
GD1b 73
766
GD1α 84
763
762
764
Fuc-GM1 87
657
292
GD1β
128
781
313
337
486
479
477
480
319
326
320
484
340
472
SB1a
357
GD1α2
322
321
Sialyl-Lea
327
493
481
GM1b 82
330
247
329
306
GM1 72
291
333
794
784
GM1α
127
GT3 68
GD2 70
309
387
325
316
314
310
373
374
393
295
785
473
798
783 95
786
475
408
474
485
804
210
asialo-GM1 81
GM2 69
332
805
GM2α
126
GD3 67
801
650
651
317
372
392
810
809
483
410
630 17
asialo-GM2
814 15
GM3
812
632
356
318
351
811
819
654
787
655
767
758
296
658
659
795
796
807
808
660
661
662
663
665
748
750
744
743
667
745
747
753 42
797
631
407 11
800
818
331
476
Ganglioside GD2
Ceramide biosynthesis
The generic definition for a “ceramide” is an N-acyl-sphingoid base. The major sphingoid bases of mammalian sphingolipids are 18-carbon amino alkanes and alkenes derived from serine and palmitoyl-CoA, and are abbreviated by the number of hydroxyls (d for di-, t for tri-, etc.), the carbon chain length and number of bonds; for example: Sphing-4-enine sphingosine) = d18:1. In the scheme below, other sphingoid bases are designated d,tA:B to reflect variation in alkyl chain length (A) (such as d20:1 in brain gangliosides and d14:1 in insects), number of double bonds (B) (such as sphingediene, 4,14-d18:2 in mammals & 4,8-d18:2 in plants) and number of hydroxyl groups (such as 4-hydroxysphinganine, phytosphingosine, 4t18:0, and 6-hydroxysphingosine, 6-t18:1, in skin). Other variations include sidechain methylation and the presence of triple bonds. The rest of Sphingomap shows possible headgroups that are added to these lipid backbones.
Ceramides & 4-Hydroxydihydroceramides (Phytoceramides)
Dihydroceramides & Other Homologs
Other sphingoid bases & fatty acids
d,tA;B;
Cx:y
d18:0;
16:0
d18:1;
20:0
t18:0;
18:0
22:0
24:1
24:0
26:1
26:0
Yeast Phytoceramide
“Ceramides”
are N-acyl-sphingoid bases. The fatty acids are designated by Cx:y to reflect chain length (x), double bonds (y), and other modifications (e.g. α-hydroxy, αh-, not shown). Other fatty acid variations include ω-hydroxylation (in skin).
Sphingosine-1P
Phosphoethanolamine
3-Ketosphinganine
L-serine
Stearoyl-CoA
or other fatty acyl-CoA’s
4-Hydroxysphinganine
Sphingosine (d18:1)
Sphinganine (d18:0)
Sphinganine-1P
Palmitoyl-CoA + or
Gal-series 3
GM4 13 1 C
GalCer 5
CDG 9 4
Gala-series
SM4s 16
Arthro-series
Glc-series
GlcCer 2 6 10
Mollu-series 14
356
SM3
LacCer 17
asialo-GM2 15
GM3 11
iGb3 7
pk antigen 12
nLc4Cer 8
Ganglio-series
Globo-series
IsoGlobo-series
Lacto-series
NeoLacto-series
Phosphosphingolipids
Phospho-series
630
IsoGanglio-series
632
Muco-series
Non-mammalian
(Phosphono-)
(Arseno-)
Ceramide phosphate
Sphingomyelin
(Ceramide phosphocholine)
Cer-O-P(O2H)-O-CH2CH2N(CH3)3
Sphingosyl-phosphocholine
Phytoceramide phosphoinositol(s)
Phytoceramide phosphoinositol-phosphate & other derivatives
Ceramide ciliatine
Ceramide arsenocholine
Ceramide phosphoethanolamine
Sulfatide
Nomenclature for classification of glycosphingolipids
Root name Carbohydrate in the ‘root’ structure
(Abbrev) IV III II I
Ganglio (Gg)
Lacto (Lc)
Neolacto (nLc)
Globo (Gb)
Isoglobo (iGb)
Mollu (Mu)
Arthro (At)
Galβ1–3GalNacβ1–4Galβ1–4Glcβ1-Cer
Galβ1–3GlcNacβ1–3Galβ1–4Glcβ1-Cer
Galβ1–4GlcNacβ1–3Galβ1–4Glcβ1-Cer
GalNacβ1–3Galα1–4Galβ1–4Glcβ1-Cer
GalNacβ1–3Galα1–3Galβ1–4Glcβ1-Cer
GalNacβ1–2Manα1–3Manβ1–4Glcβ1-Cer
GalNacβ1–4GlcNacβ1–3Manβ1–4Glcβ1-Cer
1. Merrill AH Jr, Wang MD, Park M, Sullards MC (2007) (Glyco)Sphingolipidology: an amazing challenge and opportunity for systems biology, Trends Biochem. Sci. 32:
2. Yu RK, Yanagisawa M, Ariga T (2007) Glycosphingolipid structures in Comprehensive Glycoscience, Four-Volume Set, Volume 1-4: from Chemistry to Systems Biology by J. P. Kamerling, Editor-in-Chief, Elsevier, Amsterdam.
3. Suzuki, A. (2003) Map 3. Biosynthetic pathways of glycosphingolipids in Handbook of Glycosyltransferases and Related Genes (N. Taniguchi, K. Honke, and M. Fukuda, eds) Springer (Tokyo), pp
4.KEGG Sphingophospholipid biosynthesis:
5. KEGG Sphingolycolipid metabolism:
6. Lipid Bank for Web Database:
7. Nomenclature from “Essentials of Glycobiology”as modified for 2nd. Edition: and The Consortium for Functional Glycomics,
Prepared by:
Meeyoung Park, Hyejung Park, Anu Koppikar, Akemi Suzuki, Alfred H. Merrill, Jr. and others in the Georgia Tech Sphingolipid Research Lab ( School of Biology & Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology in affiliation with the Lipid Maps Consortium & the UGA Complex Carbohydrate Research Center.
Assistance with web design and maintenance: Rebecca Lee
Acknowledgements
We thank the following for suggestions:
Eoin Fahy, Tony Futerman, Kentaro Hanada, Sen-itiroh Hakomori, Yoshio Hirabayashi, Jin-Young Hong, Michael “Hawkeye” Pierce, Konrad Sandhoff, Ronald L. Schnaar, Walt Shaw (Avanti Polar Lipids), M. Cameron Sullards, C. C. Sweeley, Elaine Wang and May Dongmei Wang
And the following for support:
the Lipid MAPS Consortium (GM69338, Ed Dennis, PI), the Smithgall Institute Endowment for Molecular Cell Biology and the Petit Institute for Bioengineering & Bioscience at Georgia Tech, and the UGA Integrated Technology Resource for Biomedical Glycomics (PA , Michael Pierce, PI).
Version 2.0
10/15/07
SphinGOMAP.orgGlyco/Ontologies/Metabolonics
Ganglioside GD1a
Galactose (Gal)
N-acetylgalactosamine (GalNAc)
Glucose (Glc)
N-acetylglucosamine (GlcNAc)
Mannose (Man)
N-acetylmannosamine (ManNAc)
Fucose
Xylose
Neuraminic Acid (Neu5Ac)
N-Glycoloyl-Neu (NeuGc)
KDN,(+)-3-deoxy-D-glycero-D-galacto-2-nonulosonic acid
Glucuronyl (GlcU)
Sphingosine
SO4
NeuNH2
HSO3
Ac-O
GlcNH2
Ceramide
1.The numbers within the symbols represent the carbon connectivity
2. Underlined numbers have alpha (α) linkage
3. Plain numbers have beta (β) linkage S
*SphinGOMAP is an evolving pathway map for sphingolipid biosynthesis that includes many of the known sphingolipids and glycosphingolipids arranged according to their biosynthetic steps [1-7] or, in the cases where the biosynthetic enzymes have not yet been identified, in hypothetical pathways. It is hoped that this pathway will promote dialog about the “knowns” and “unknowns” of sphingolipid biosynthesis and lead to experiments to refine this model. Users may print or modify the map for personal use if the source is appropriately acknowledged; for other uses, or to recommend corrections or additions, contact Dr. Al Merrill at (please refer to the version of SphinGOMAP and the compounds by molecule number and map coordinates). C U
Documented Molecule*
Undocumented Molecule
Molecule Number (SM ID)
Documented Pathway*
Undocumented Pathway
*See notes in box … 1 C 1 C … 2
Ganglio-series
SphinGOMAP.org A B C D E F G H I J K L M N O P Q R