Transcript 3 - SphinGOMAP - Georgia Institute of Technology

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1
3 3 4 4 1 C
8 3 3 4 4 1 C
GM1b
8 8 3 3 4 4 1 C
8 8 8 3 3 4 4 1 C
750
GD1c
82
8 3 4 4 1 C
3
3
4 1 C
GM1
3
4 1 C
GD1a
8 3
3 4 4 1 C
3
8 3 3
3
3
8 3 3 4
4
660
9 8 3
657
6
8 3
4
3
3
4 1 C
GD1aα
88
4 4 1 C
8 8 3 4 1 C
GD3
GT3
8 8 3
8 8 3
4 1 C
GT2
8 3
4 1 C
3
2 4 4 1 C
HO
NHAc
4 4 1 C
GD1α
HO
3 3 3 3 4
3 3
3
6 3
4 1 C
3
4 1 C
GT1aα
Ceramide biosynthesis
217
90
472
3 3 3 4
8 6
8 6
8 3
4 4 1 C
4 4 1 C
GD1β
335
3 3
342
128
3 3 4 4 1 C
3 3 3 3 4 4 1 C
3 3 3 4 4 1 C
765
3 4 3 3 4
4 1 C
4 1 C
4 1 C
3
3
3
653
652
294
3 3 3 4
3 3 3 4 4 1 C
3 4 3 3 4
4 1 C
766
4 1 C
3
3 3 4 4 1 C
4 1 C
787
323
3 3 4
3
654
8 3
2 3 4
309
3
4 1 C
Gal-GD1b
3 4
+
4 1 C
2 3 4
8 3
3 4 4 1 C
3
4 1 C
Fuc-GD1b
3-Ketosphinganine
4
3 3 4
3
4 1 C
Sphingosine (d18:1)
3
8
3
348
4 1 C
3
Dihydroceramides & Other Homologs
3
4 1 C
2
2 3 4
3 4
9
d18:0;
16:0
3 4
767
3
d18:0;
18:0
d18:0;
20:0
d18:0;
22:0
d18:0;
24:1
d18:0;
24:0
d18:0;
26:1
d18:0;
26:0
d,tA;B;
Cx:y
d18:0;
Cx:y
655
d18:1; t18:0; d18:1; t18:0; d18:1; t18:0; d18:1; t18:0; d18:1; t18:0; d18:1; t18:0; d18:1; t18:0; d18:1; t18:0; d18:1; t18:0;
16:0
16:0
18:0
18:0
20:0
20:0
22:0
22:0
24:1
24:1
24:0
24:0
26:1
26:1
26:0
26:0
Cx:y Cx:y
4 1 C
3
4 1 C
3 3
337
3
3 4 4 1 C
Yeast
Phytoceramide
Ceramides & 4-Hydroxydihydroceramides (Phytoceramides)
2
333
332
4-Hydroxysphinganine
4 1 C
2
3 3 4
3
Sphinganine (d18:0)
Sphinganine-1P
299
3 4
311
4 1 C
Stearoyl-CoA
or other fatty acylCoA’s
Sphingosine-1P
3
2
4
or
Palmitoyl-CoA
3 3
93
8
7
371
4 1 C
Fuc-GM1
87
3
Phosphoethanolamine
4
92
2 3 4 4 1 C
L-serine
3
756
3 3 4
4 1 C
8 3
336
3 3 3 4
3 3 4
7
2
755
6
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.
3
3 4
310
Ganglioside GD2
5
4 1 C
6
O
OH
344
6
4 4 1 C
3
4
O
4 4 1 C
GQ1β
8 3 3
754
6
Cer
OH
8 6
6 4
4
786
O
OH
O
94
343
84
8 6 4 4 1 C
O
HO
O
4 1 C
GQ1bα
8 3
8 8 3
473
O
4 1 C
3 3
4 1 C
6 3 4 4 1 C
HO
AcHN
6
8 3 3
4 1 C
Fuc-GD1b
326
6
3 3
OH
O
OH
4
785
801
HO
749
4 4 1 C
2 4
CO O H
HO
4 1 C
GT1c
6
68
2 4
HO
4 1 C
4 1 C
GQ1c
3
8 8 3
74
71
67
3 3
8 8 3
O
4
3 4
4
O
6
753
95
3
4 1 C
3
764
HO
AcHN
663
77
8 3
9 8 3 4 1 C
CO O H
666
8 8 3
8 3
6
HO
9 8 3
3 3 4
6
HO
4
97
4 1 C
GT1b
4
4
80
6
4 1 C
GT1b
9 8 3
76
127
8 3 4 1 C
3 3 4
3 3 4
69
4 4 1 C
GM1α
4 1 C
GP1c
9 8 3
4 1 C
3
8 8 3
4 1 C
78
4 1 C
6
744
8 3 3 4
4 1 C
GQ1b
8 3
3 4
126
5
664
752
763
4 1 C
GM2
www.lipidmaps.org
8 8 3
8 3 3 4
4 1 C
GQ1aα
4 1 C
8 3
4
4 1 C
8 3
8 3
4 1 C
784
S
8 8 3 3 4
4 1 C
665
4
6 4
GM2α
3
8 8 3 3 4
4
4 1 C
6 4 4 1 C
2
478
4 1 C
6
6
73
3
4 1 C
746
290
751
4
8 3 3
8 8 3
4 1 C
4
8 3
4 1 C
4 1 C
GD1b
6 4
81
8 3 3
8 3
8 3
3 4
E
W
667
6
4
8 3
4 1 C
GD2
743
6
6
8 3 4
75
70
asialo-GM1
4 1 C
GT1a
79
4
8 3
3
748
3 3 4
72
745
8 3 3 4
762
8 8 3
4 1 C
204
3 4
4 1 C
8 3
8 8 3 3 4
4 1 C
3
8 8 8 3 3 4
4 1 C
3
8 3 4
783
8 8 8 3 3 4
4 1 C
130
9 8 3 3 4 4 1 C
2
8 8 8 3 3 4
747
1
3 3 3 4 4 1 C
Other
sphingoid
bases &
fatty acids
312
313
“Ceramides”
3 3
3 4 4 1 C
3 3 3 4 4 1 C
4 3 3 4 4 1 C
292
Phosphosphingolipids
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).
2
768
9
482
3 4 3 3 4 4 1 C
Sphingomyelin
293
Sphingosyl-phosphocholine
(Ceramide phosphocholine)
Cer-O-P(O2H)-O-CH2CH2N(CH3)3
3 3 4 4 1 C
Phospho-series
295
10
4 4 1 C
3 4 3 3 4 4 1 C
asialo-GM2
3 3 4 4 1 C
17
291
3 3 4
4 1 C
4 3 3 4
404
GM3
3 3 4 1 C
SM4s
GalCer
3
(Phosphono-)
1 C
Ceramide ciliatine
GM4
3 4
397
13
3 3 4 1 C
4
365
Gala-series
3 3 4 1 C
3
3 4 1 C
4
375
11
4
374
396
4 1 C
395
392
10
4
4 1 C
3 3
393
Glc-series
3 4 3 3
4
761
4 1 C
4 3 3
Non-mammalian
4 1 C
6
1 C
4
Arthro-series
4 4 1 C
GlcCer
394
12
Mollu-series
3 4 1 C
3 3 3
4 1 C
3
9
3
4
4
11
CDG
4 1 C
4 1 C
4
Ceramide arsenocholine
4 1 C
3 3
3 3 3 4 1 C
Non-mammalian
(Arseno-)
3
812
Phytoceramide phosphoinositolphosphate & other derivatives
Ceramide phosphate
16
1 C
5
3 4 3 3 4 1 C
373
372
3 4 1 C
Gal-series
4 1 C
3
296
4 3 3 4 1 C
Phytoceramide phosphoinositol(s)
3 1 C
3
15
10
Sulfatide
758
3 4 1 C
11
Ceramide phosphoethanolamine
14
2
12
3 3 4 4 1 C
3
3 3 3 4 4 1 C
298
297
356
4 1 C
4 1 C
4
302
300
477
3 4 1 C
4 1 C
3
GM3
4 1 C
301
8 3 3 4 4 1 C
15
LacCer
480
3
9 3 3 4
3
9 3 3 4 4 1 C
773
3
630
661
4 4 1 C
4
3 3 4
3
3
3
345
4 3 4
3
GalNAc-GM1
481
7
4 1 C
GalNAcGD1a
91
14
3 4 1
C
11
3 4
3
3
86
4 1 C
GalNAcGD1a 308
4 4 1
Muco-series
C
632
4
3 4 4 1 C
IsoGlobo-series
iGb3
4
4 1 C
Globo-series
pk antigen
3 4
4 1 C
4 3 4 4 1 C
IsoGanglio-series
3 4 1 C
4 1 C
8 3
319
14
17
3 3 4
4 1 C
GD1a
13
asialo-GM2
334
3 3 4
Ganglio-series
4 4 1 C
4 1 C
314
nLc4Cer
12
3 3 3 4
8 3 3 4 4 1 C
3 3 4 4 1 C
NeoLacto-series
4 3 4 1 C
3 4 1 C
3
3
13
8
4 3 3 4
306
Lacto-series
3 3 4 1 C
SM3
3 3 4
3 3 4 4 1 C
3 4 1 C
3 4
3
3 4 4 1 C
307
3
341
15
15
3 4 3 4 4 1 C
629
Nomenclature for classification of glycosphingolipids
Root name
Carbohydrate in the ‘root’ structure
(Abbrev)
IV
III
II
I
3 3 3 4
4 1 C
3
3 3 3 4 4 1 C
339
774
3 3 3 4
3 3 3 4 4 1 C
775
4 1 C
3
Ganglio (Gg)
Lacto (Lc)
Neolacto (nLc)
Globo (Gb)
Isoglobo (iGb)
349
3 3 4
4
4 1 C
4 1 C
16
4
3
3
4
210
4 1 C
4 3
338
3
269
4
4 3 4 1 C
3 4 3 4 1 C
3
3 4
42
3 4 1 C
4
3
85
4
3 4 3
4
4 1 C
268
4
9 8 8 3
4 1 C
3 4 1 C
4 3
630
4
17
407
96
3
4 4 1 C
6
4
483
814
402
9 8 8 3 4 1 C
4 1 C
17
4
3
4 1 C
4 1 C
8 3
4 4 3
GT1bα
324
501
4
4 1 C
4 4 1 C
3
632
6 4
3
3
779
4 1 C
8 3
8 3
3 3 4
4 1 C
4 1 C
780
8 3
4
331
4 1 C
304
4 3 4
4 3
4 1 C
4 3 4 1 C
330
3
3 3 4
476
4 1 C
781
8 3
662
3 3 4
3 3 4 1 C
3
3 3 3 4 1 C
631
4 1 C
GD1a
8 3
8 3
658
795
3 4
4
4 1 C
4 1 C
8 3 4 1 C
8 3
8 3
808
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-02-132,
Michael Pierce, PI).
328
4 1 C
4 1 C
807
4 1 C
3
3 4
4
8 3 4 1 C
9 3 3 4
303
475
19
Prepared by:
Meeyoung Park, Hyejung Park, Anu Koppikar, Akemi Suzuki, Alfred H.
Merrill, Jr. and others in the Georgia Tech Sphingolipid Research Lab
(http://sphingolab.biology.gatech.edu), 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
4 1 C
4
3
4 1 C
GalNAcGD1a 305
3 4
794
18
3 4
8 3
4
805
659
796
3
2 3 3 4 1 C
3 3 4 1 C
797
2
484
20
6 4 4 1 C
3 6 4 4 1 C
809
408
6
4 4 1 C
GD1α2
3 3
6 6 4 4 1 C
322
474
3 3 4
3 4
3
4 1 C
3
3 4 1 C
SphinGOMAP.org
316
9 3 3 4 4 1 C
21
Galactose (Gal)
*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
[email protected] (please refer to the version of SphinGOMAP
and the compounds by molecule number and map coordinates).
782
3 4 4 1 C
3 3 4
3 4
4 1 C
4 1 C
651
3
3
320
485
6 4 4 1 C
6
6
810
4 4 1 C
3
4
4 4 1 C
GD1α2
3 3
321
798
4 1 C
3 4 1 C
3
356
3 3 4
3 4
650
4 1 C
3
3
4
4 1 C
GD1a
340
351
3
819
S
Version 2.0
10/15/07
20
Sphingosine
N-acetylgalactosamine (GalNAc)
SO4
Glucose (Glc)
NeuNH2
N-acetylglucosamine (GlcNAc)
HSO3
Mannose (Man)
Ac-O
N-acetylmannosamine (ManNAc)
GlcNH2
Fucose
C
Xylose
21
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
Neuraminic Acid (Neu5Ac)
N-Glycoloyl-Neu (NeuGc)
KDN,(+)-3-deoxy-D-glycero-D-galacto-2nonulosonic acid
U
4 1 C
3 4 1 C
19
Ganglioside GD1a
317
318
18
Glyco/Ontologies/Metabolonics
4 1 C
3 KDN-GD1a
315
4 1 C
4
1. Merrill AH Jr, Wang MD, Park M, Sullards MC (2007) (Glyco)Sphingolipidology: an amazing
challenge and opportunity for systems biology, Trends Biochem. Sci. 32:457-468.
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. 636-646.
4.KEGG Sphingophospholipid biosynthesis: http://www.biologie.uni-hamburg.de/bonline/kegg/kegg/Classes/dblinks_java/map/map00570.html
5. KEGG Sphingolycolipid metabolism: http://www.biologie.uni-hamburg.de/bonline/kegg/kegg/Classes/dblinks_java/map/map00600.html
6. Lipid Bank for Web Database: http://www.lipidbank.jp/
7. Nomenclature from “Essentials of Glycobiology”as modified for 2nd. Edition:
http://grtc.ucsd.edu/symbol.html and The Consortium for Functional Glycomics,
http://www.functionalglycomics.org/static/index.shtml
4
4 1 C
410
8 3 4 1 C
22
GalNacβ1–2Manα1–3Manβ1–4Glcβ1-Cer
GalNacβ1–4GlcNacβ1–3Manβ1–4Glcβ1-Cer
Mollu (Mu)
Arthro (At)
4 1 C
493
804
16
3 4 4 1 C
253
4 4 3 4 1 C
4 3 4 1 C
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
22
Glucuronyl (GlcU)
…
1 C
…
1 C
Documented Molecule*
Documented Pathway*
Undocumented Molecule
Undocumented Pathway
Molecule Number (SM ID)
*See notes in box
4
811
3
3 4 4 1 C
GalNAc-GM1b
4 4 4 1 C
83
818
3 3 4
4 1 C
3 3 4 4 1 C
3
387
23
2
23
486
3 4
Ganglio-series
3 3 4
4 1 C
3
3
325
4 1 C
SB1a
357
4
4 1 C
3 4 3 4 1 C
3 4 3
329
4
24
247
4
4 4 1 C
3
3 3
800
24
4 4 1 C
Sialyl-Lea
327
8 3 3 4 4 1 C
479
SphinGOMAP.org
25
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