85533
Pathway
Succinate Signalling During Inflammation
Succinate induces calcium mobilization in an adenylyl cyclase (AC) and protein kinase A (PKA)-dependent manner. Succinate receptor 1 (SUCNR1) engagement activates phospholipase C (PLC), resulting in the cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG). These second messengers induce calcium mobilization and PKC activation, respectively, and subsequent nitric oxide (NO) and prostaglandin E2 (PGE2) production as well as p38 activation. PKC-dependent phosphorylation of extracellular signal-related kinases ERK1/2 can also drive PG production. SUCNR1 signaling might act in synergy with several inflammatory signaling cascades. PKA is known to phosphorylate and activate the p65 subunit of nuclear factor κB (NF-κB) and cAMP response element-binding protein (CREB). Furthermore, NF-κB, activating protein (AP)-1, nuclear factor of activated T cells (NFAT), and ETS domain-containing protein (Elk-1) are all downstream targets of PKC and MAPKs.
Protein
PW085652
Center
PathwayVisualizationContext85928
2100
1750
#000099
PathwayVisualization85408
85533
Succinate Signalling During Inflammation
Succinate induces calcium mobilization in an adenylyl cyclase (AC) and protein kinase A (PKA)-dependent manner. Succinate receptor 1 (SUCNR1) engagement activates phospholipase C (PLC), resulting in the cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG). These second messengers induce calcium mobilization and PKC activation, respectively, and subsequent nitric oxide (NO) and prostaglandin E2 (PGE2) production as well as p38 activation. PKC-dependent phosphorylation of extracellular signal-related kinases ERK1/2 can also drive PG production. SUCNR1 signaling might act in synergy with several inflammatory signaling cascades. PKA is known to phosphorylate and activate the p65 subunit of nuclear factor κB (NF-κB) and cAMP response element-binding protein (CREB). Furthermore, NF-κB, activating protein (AP)-1, nuclear factor of activated T cells (NFAT), and ETS domain-containing protein (Elk-1) are all downstream targets of PKC and MAPKs.
Protein
1
261488
24361092
Mills E, O'Neill LA: Succinate: a metabolic signal in inflammation. Trends Cell Biol. 2014 May;24(5):313-20. doi: 10.1016/j.tcb.2013.11.008. Epub 2013 Dec 19.
85533
Pathway
261489
25352636
McCreath KJ, Espada S, Galvez BG, Benito M, de Molina A, Sepulveda P, Cervera AM: Targeted disruption of the SUCNR1 metabolic receptor leads to dichotomous effects on obesity. Diabetes. 2015 Apr;64(4):1154-67. doi: 10.2337/db14-0346. Epub 2014 Oct 28.
85533
Pathway
1
Cell
CL:0000000
2
Platelet
CL:0000233
4
Cardiomyocyte
CL:0000746
3
Neuron
CL:0000540
8
Beta cell
CL:0000639
5
Hepatocyte
CL:0000182
1
Homo sapiens
9606
Eukaryote
Human
18
Saccharomyces cerevisiae
4932
Eukaryote
Yeast
4
Arabidopsis thaliana
3702
Eukaryote
Thale cress
12
Mus musculus
10090
Eukaryote
Mouse
5
Bos taurus
9913
Eukaryote
Cattle
17
Rattus norvegicus
10116
Eukaryote
Rat
10
Drosophila melanogaster
7227
Eukaryote
Fruit fly
6
Caenorhabditis elegans
6239
Eukaryote
Roundworm
3
Escherichia coli
562
Prokaryote
24
Solanum lycopersicum
4081
Eukaryote
Tomato
21
Xenopus laevis
8355
Eukaryote
African clawed frog
23
Pseudomonas aeruginosa
287
Prokaryote
60
Nitzschia sp.
0001
Eukaryote
Nitzschia4
49
Bathymodiolus platifrons
220390
Eukaryote
Deep sea mussel
2
Bacteria
2
Prokaryote
Bacteria
19
Schizosaccharomyces pombe
4896
Eukaryote
62
Acinetobacter baylyi (strain ATCC 33305 / BD413 / ADP1)
62977
Prokaryote
5
Cytoplasm
GO:0005737
1
Cytosol
GO:0005829
7
Endoplasmic Reticulum Membrane
GO:0005789
10
Cell Membrane
GO:0005886
11
Extracellular Space
GO:0005615
19
sarcoplasmic reticulum
GO:0016529
2
Mitochondrion
GO:0005739
24
Mitochondrial Intermembrane Space
GO:0005758
25
Golgi apparatus
GO:0005794
14
Mitochondrial Outer Membrane
GO:0005741
12
Mitochondrial Inner Membrane
GO:0005743
13
Endoplasmic Reticulum
GO:0005783
6
Lysosome
GO:0005764
16
Lysosomal Lumen
GO:0043202
36
Membrane
GO:0016020
3
Mitochondrial Matrix
GO:0005759
4
Peroxisome
GO:0005777
31
Periplasmic Space
GO:0005620
27
Peroxisome Membrane
GO:0005778
15
Nucleus
GO:0005634
26
Golgi apparatus membrane
GO:0000139
35
Chloroplast
GO:0009507
20
Endoplasmic Reticulum Lumen
GO:0005788
8
Smooth Endoplasmic Reticulum
GO:0005790
34
Plant-Type Vacuole
GO:0000325
39
Mitochondrial membrane
GO:0031966
2
Endothelium
BTO:0000393
5
cardiocyte
BTO:0001539
1
Liver
BTO:0000759
72
9
18
Pancreas
BTO:0000988
8
Blood Vessel
BTO:0001102
74
11
7
Nervous System
BTO:0001484
8
5
1
1
PW_BS000008
2
1
1
1
PW_BS000002
160
1
18
1
PW_BS000160
198
5
18
1
PW_BS000024
151
1
4
1
PW_BS000151
111
5
12
1
PW_BS000111
132
1
12
1
PW_BS000132
122
5
5
1
PW_BS000122
124
1
5
1
PW_BS000124
135
5
17
1
PW_BS000135
118
1
17
1
PW_BS000118
297
5
10
1
PW_BS000024
299
1
10
1
PW_BS000024
205
5
6
1
PW_BS000024
388
1
6
1
PW_BS000112
49
7
1
1
PW_BS000049
331
7
12
1
PW_BS000028
383
7
5
1
PW_BS000100
390
7
6
1
PW_BS000112
398
7
17
1
PW_BS000113
16
2
1
2
PW_BS000016
14
10
1
PW_BS000014
15
11
1
PW_BS000015
21
5
1
1
4
PW_BS000021
35
5
19
1
4
PW_BS000035
3
2
1
1
PW_BS000003
46
1
1
4
PW_BS000046
47
19
1
4
PW_BS000047
42
24
1
1
PW_BS000042
43
25
1
1
PW_BS000043
58
1
14
1
1
PW_BS000058
17
12
1
1
PW_BS000017
18
13
1
1
PW_BS000018
9
6
1
1
PW_BS000009
71
11
1
3
PW_BS000071
72
5
1
3
PW_BS000072
29
1
1
1
PW_BS000029
66
18
5
1
8
PW_BS000066
10
1
7
1
1
PW_BS000010
28
1
16
1
1
PW_BS000028
101
5
3
1
PW_BS000101
211
10
18
PW_BS000024
190
11
18
PW_BS000024
213
7
18
1
PW_BS000024
210
13
18
1
PW_BS000024
164
4
PW_BS000164
285
10
4
1
PW_BS000024
308
10
1
1
PW_BS000024
1
1
PW_BS000001
115
10
12
PW_BS000115
356
25
12
1
PW_BS000028
345
24
12
1
PW_BS000028
130
13
12
1
PW_BS000130
114
11
12
PW_BS000114
74
1
3
PW_BS000074
228
36
1
PW_BS000024
51
8
1
PW_BS000051
405
10
5
PW_BS000115
418
24
5
1
PW_BS000115
419
25
5
1
PW_BS000115
125
13
5
1
PW_BS000125
409
11
5
PW_BS000115
376
10
17
PW_BS000053
454
24
17
1
PW_BS000115
455
25
17
1
PW_BS000115
136
13
17
1
PW_BS000136
137
11
17
PW_BS000137
478
10
10
PW_BS000115
489
24
10
1
PW_BS000115
490
25
10
1
PW_BS000115
495
7
10
1
PW_BS000115
209
10
6
PW_BS000024
506
24
6
1
PW_BS000115
507
25
6
1
PW_BS000115
4
3
1
1
PW_BS000004
31
1
5
1
1
PW_BS000031
5
4
1
1
PW_BS000005
103
3
3
1
PW_BS000103
155
3
24
1
PW_BS000155
161
3
18
1
PW_BS000161
107
31
3
PW_BS000107
108
1
3
PW_BS000108
178
3
21
1
PW_BS000178
117
1
3
1
PW_BS000117
166
1
1
PW_BS000166
163
2
18
1
PW_BS000163
219
31
4
PW_BS000024
220
1
4
PW_BS000024
222
3
4
1
PW_BS000024
223
12
4
1
PW_BS000024
318
31
23
PW_BS000024
315
1
23
PW_BS000024
322
1
23
1
PW_BS000024
133
3
12
1
PW_BS000133
134
12
12
1
PW_BS000134
112
2
12
1
PW_BS000112
129
1
5
12
1
PW_BS000129
334
4
12
1
PW_BS000028
368
3
60
1
PW_BS000028
119
2
17
1
PW_BS000119
406
3
5
1
PW_BS000115
407
2
5
1
PW_BS000115
414
1
5
5
1
PW_BS000115
408
4
5
1
PW_BS000115
384
12
5
1
PW_BS000100
120
3
17
1
PW_BS000120
450
1
5
17
1
PW_BS000115
374
4
17
1
PW_BS000053
121
12
17
1
PW_BS000121
479
3
10
1
PW_BS000115
481
2
10
1
PW_BS000115
482
4
10
1
PW_BS000115
480
12
10
1
PW_BS000115
501
3
6
1
PW_BS000115
206
2
6
1
PW_BS000024
502
4
6
1
PW_BS000115
391
12
6
1
PW_BS000112
26
1
1
1
5
PW_BS000026
22
14
1
1
PW_BS000022
39
7
1
1
3
PW_BS000039
59
27
1
1
PW_BS000059
23
15
1
1
PW_BS000023
7
1
1
PW_BS000007
91
8
5
1
1
PW_BS000091
54
1
3
1
5
PW_BS000054
56
26
1
1
PW_BS000056
104
14
3
1
PW_BS000104
147
1
24
1
PW_BS000147
199
14
18
1
PW_BS000024
214
25
18
1
PW_BS000024
216
4
18
1
PW_BS000024
225
35
4
1
PW_BS000024
249
13
4
1
PW_BS000024
288
14
4
1
PW_BS000024
226
4
4
1
PW_BS000024
290
5
49
1
PW_BS000024
329
14
12
1
PW_BS000028
336
1
12
1
PW_BS000028
335
27
12
1
PW_BS000028
184
1
2
1
PW_BS000024
372
10
2
PW_BS000028
253
5
4
1
PW_BS000024
27
15
1
PW_BS000027
382
14
5
1
PW_BS000100
429
1
5
1
PW_BS000115
422
27
5
1
PW_BS000115
399
14
17
1
PW_BS000113
464
1
17
1
PW_BS000115
375
27
17
1
PW_BS000053
484
14
10
1
PW_BS000115
491
27
10
1
PW_BS000115
300
13
10
1
PW_BS000024
389
14
6
1
PW_BS000112
508
27
6
1
PW_BS000115
395
13
6
1
PW_BS000113
36
1
20
1
1
PW_BS000036
11
1
8
1
1
PW_BS000011
95
1
7
2
1
PW_BS000095
123
1
7
5
1
PW_BS000123
141
1
7
19
1
PW_BS000141
78
8
1
1
PW_BS000078
298
1
7
10
1
PW_BS000024
293
4
1
PW_BS000024
332
1
7
12
1
PW_BS000028
447
1
7
17
1
PW_BS000115
13
1
2
1
PW_BS000013
6
1
3
1
PW_BS000006
102
12
3
1
PW_BS000102
126
6
5
1
PW_BS000126
127
1
16
5
1
PW_BS000127
156
12
24
1
PW_BS000156
162
12
18
1
PW_BS000162
179
12
21
1
PW_BS000179
224
2
4
1
PW_BS000024
215
6
18
1
PW_BS000024
227
34
4
1
PW_BS000024
291
6
49
1
PW_BS000024
292
4
49
1
PW_BS000024
301
6
10
1
PW_BS000024
302
1
16
10
1
PW_BS000024
113
6
12
1
PW_BS000113
337
1
16
12
1
PW_BS000028
358
39
12
PW_BS000028
369
12
60
1
PW_BS000028
443
6
17
1
PW_BS000115
448
1
16
17
1
PW_BS000115
207
6
6
1
PW_BS000024
89
2
PW_BS000089
653
1
62
4
PW_BS000508
665
18
1
8
PW_BS000508
6123
PIP2(18:1(11Z)/20:3(8Z,11Z,14Z))
HMDB0010082
PIP2(18:1(11Z)/20:3(8Z,11Z,14Z)) is a phosphatidylinositol bisphosphate. Phosphatidylinositol bisphosphates are acidic (anionic) phospholipids that consist of a phosphatidic acid backbone, linked via the phosphate group to a bisphosphorylated inositol (hexahydroxycyclohexane). Phosphatidylinositol bisphosphates are generated from phosphatidylinositols which are phosphorylated by a number of different kinases that place the phosphate moiety on positions 4 and 5 of the inositol ring, although position 3 can also be phosphorylated. Phosphatidylinositols bisphosphates can have many different combinations of fatty acids of varying lengths and saturation attached at the C-1 and C-2 positions. Fatty acids containing 18 and 20 carbons are the most common. PIP2(18:1(11Z)/20:3(8Z,11Z,14Z)), in particular, consists of one chain of vaccenic acid at the C-1 position and one chain of homo-g-linolenic acid at the C-2 position. The vaccenic acid moiety is derived from butter fat and animal fat, while the homo-g-linolenic acid moiety is derived from fish oils, liver and kidney. The most important phosphatidylinositol bisphosphate in both quantitative and biological terms is phosphatidylinositol 4,5-bisphosphate. Phosphatidylinositol and the phosphatidylinositol phosphates are the main source of diacylglycerols that serve as signaling molecules, via the action of phospholipase C enzymes. Phosphatidylinositols phosphates are usually present at low levels only in tissues, typically at about 1 to 3% of the concentration of phosphatidylinositol.
C00626
53480273
Phosphatidylinositols
24767959
CCCCCC\C=C/CCCCCCCCCC(=O)OC[C@]([H])(COP(O)(=O)O[C@H]1C(O)C(O)C(OP(=O)(O)O)[C@@H](OP(=O)(O)O)C1O)OC(=O)CCCCCC\C=C/C\C=C/C\C=C/CCCCC
C47H85O19P3
InChI=1S/C47H85O19P3/c1-3-5-7-9-11-13-15-17-19-20-22-24-26-28-30-32-34-36-41(49)63-39(37-61-40(48)35-33-31-29-27-25-23-21-18-16-14-12-10-8-6-4-2)38-62-69(59,60)66-45-42(50)43(51)46(64-67(53,54)55)47(44(45)52)65-68(56,57)58/h11,13-14,16-17,19,22,24,39,42-47,50-52H,3-10,12,15,18,20-21,23,25-38H2,1-2H3,(H,59,60)(H2,53,54,55)(H2,56,57,58)/b13-11-,16-14-,19-17-,24-22-/t39-,42?,43?,44?,45+,46?,47+/m1/s1
QMRUSFNQFVPOME-RZEZUQAISA-N
{[(4S,6S)-2,3,5-trihydroxy-4-({hydroxy[(2R)-2-[(8Z,11Z,14Z)-icosa-8,11,14-trienoyloxy]-3-[(11Z)-octadec-11-enoyloxy]propoxy]phosphoryl}oxy)-6-(phosphonooxy)cyclohexyl]oxy}phosphonic acid
1047.0877
1046.489790074
-4.60
8
[(4S,6S)-2,3,5-trihydroxy-4-{[hydroxy(2R)-2-[(8Z,11Z,14Z)-icosa-8,11,14-trienoyloxy]-3-[(11Z)-octadec-11-enoyloxy]propoxyphosphoryl]oxy}-6-(phosphonooxy)cyclohexyl]oxyphosphonic acid
0
-5
C00626
1-(11z-octadecenoyl)-2-(8z,11z,14z-eicosatrienoyl)-sn-glycero-3-phospho-(1'-myo-inositol-3',4'-bisphosphate);1-phosphatidyl-d-myo-inositol 4,5-bisphosphate;1-phosphatidyl-delta-myo-inositol 4,5-bisphosphate;1-vaccenoyl-2-homo-g-linolenoyl-sn-glycero-3-phosphoinositol-bisphosphate;1-vaccenoyl-2-homo-gamma-linolenoyl-sn-glycero-3-phosphoinositol-bisphosphate;Pip2(18:1/20:3);Pip2(18:1n7/20:3n6);Pip2(18:1w7/20:3w6);Pip2(38:4);Pip2[3',4'](18:1(11z)/20:3(8z,11z,14z));Phosphatidylinositol diphosphate(18:1/20:3);Phosphatidylinositol diphosphate(18:1n7/20:3n6);Phosphatidylinositol diphosphate(18:1w7/20:3w6);Phosphatidylinositol diphosphate(38:4)
PW_C006123
PIP211
113030
8
892
Inositol 1,3,4-trisphosphate
HMDB0001143
Inositol 1,3,4-trisphosphate, also known as 1,3,4-itp or I3S, belongs to the class of organic compounds known as inositol phosphates. Inositol phosphates are compounds containing a phosphate group attached to an inositol (or cyclohexanehexol) moiety. Inositol 1,3,4-trisphosphate is soluble (in water) and an extremely strong acidic compound (based on its pKa). Within the cell, inositol 1,3,4-trisphosphate is primarily located in the cytoplasm. In humans, inositol 1,3,4-trisphosphate is involved in the inositol metabolism pathway and the inositol phosphate metabolism pathway. Inositol 1,3,4-trisphosphate is a specific regulator of cellular signaling.
98102-63-7
C01243
439455
18228
INOSITOL-1-3-4-TRIPHOSPHATE
388561
DB01729
O[C@@H]1[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@@H](O)[C@H]1OP(O)(O)=O
C6H15O15P3
InChI=1S/C6H15O15P3/c7-1-2(8)5(20-23(13,14)15)6(21-24(16,17)18)3(9)4(1)19-22(10,11)12/h1-9H,(H2,10,11,12)(H2,13,14,15)(H2,16,17,18)/t1-,2-,3+,4+,5+,6+/m1/s1
MMWCIQZXVOZEGG-MLQGYMEPSA-N
{[(1S,2R,3R,4S,5S,6S)-2,3,5-trihydroxy-4,6-bis(phosphonooxy)cyclohexyl]oxy}phosphonic acid
420.0956
419.962379346
-1.45
9
inositol 1,3,4-trisphosphate
0
-6
FDB022450
1,3,4-itp;1d-myo-inositol 1,3,4-trisphosphate;D-myo-inositol 1,3,4-trisphosphate;I3s;Inositol 1,3,4-triphosphate;Inositol 1,3,4-trisphosphate;Myo-inositol 1,3,4-trisphosphate;D-myo-inositol 1,3,4-trisphosphoric acid;Inositol 1,3,4-trisphosphoric acid
PW_C000892
InoTrip
2056
8
2440
2
7385
160
7419
198
12223
151
78185
111
78210
132
121998
122
122441
124
124551
135
125008
118
126147
297
126592
299
127754
205
128164
388
3163
DG(16:0/20:4(5Z,8Z,11Z,14Z)/0:0)
HMDB0007112
DG(16:0/20:4(5Z,8Z,11Z,14Z)/0:0) is a diglyceride, or a diacylglycerol (DAG). It is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Diacylglycerols can have many different combinations of fatty acids attached at both the C-1 and C-2 positions. DG(16:0/20:4(5Z,8Z,11Z,14Z)/0:0), in particular, consists of one chain of palmitic acid at the C-1 position and one chain of arachidonic acid at the C-2 position. The palmitic acid moiety is derived from fish oils, milk fats, vegetable oils and animal fats, while the arachidonic acid moiety is derived from animal fats and eggs. Mono- and diacylglycerols are common food additives used to blend together certain ingredients, such as oil and water, which would not otherwise blend well. Dacylglycerols are often found in bakery products, beverages, ice cream, chewing gum, shortening, whipped toppings, margarine, and confections. Synthesis of diacylglycerol begins with glycerol-3-phosphate, which is derived primarily from dihydroxyacetone phosphate, a product of glycolysis (usually in the cytoplasm of liver or adipose tissue cells). Glycerol-3-phosphate is first acylated with acyl-coenzyme A (acyl-CoA) to form lysophosphatidic acid, which is then acylated with another molecule of acyl-CoA to yield phosphatidic acid. Phosphatidic acid is then de-phosphorylated to form diacylglycerol.Diacylglycerols are precursors to triacylglycerols (triglyceride), which are formed by the addition of a third fatty acid to the diacylglycerol under the catalysis of diglyceride acyltransferase. Since diacylglycerols are synthesized via phosphatidic acid, they will usually contain a saturated fatty acid at the C-1 position on the glycerol moiety and an unsaturated fatty acid at the C-2 position.
C00165
9543736
77096
DIACYLGLYCEROL
7822686
[H][C@](CO)(COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC
C39H68O5
InChI=1S/C39H68O5/c1-3-5-7-9-11-13-15-17-18-19-20-22-24-26-28-30-32-34-39(42)44-37(35-40)36-43-38(41)33-31-29-27-25-23-21-16-14-12-10-8-6-4-2/h11,13,17-18,20,22,26,28,37,40H,3-10,12,14-16,19,21,23-25,27,29-36H2,1-2H3/b13-11-,18-17-,22-20-,28-26-/t37-/m0/s1
YJEMDFYSDGNQNM-NDUZERMISA-N
(2S)-1-(hexadecanoyloxy)-3-hydroxypropan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate
616.9542
616.506675286
-7.58
1
diacylglycerol
0
0
FDB024306
1-palmitoyl-2-arachidonoyl-sn-glycerol;Dag(16:0/20:4);Dag(16:0/20:4n6);Dag(16:0/20:4w6);Dag(36:4);Dg(16:0/20:4);Dg(16:0/20:4n6);Dg(16:0/20:4w6);Dg(36:4);Diacylglycerol;Diacylglycerol(16:0/20:4);Diacylglycerol(16:0/20:4n6);Diacylglycerol(16:0/20:4w6);Diacylglycerol(36:4);Diglyceride;(2s)-1-hydroxy-3-(palmitoyloxy)propan-2-yl (5z,8z,11z,14z)-icosa-5,8,11,14-tetraenoate;1,2-dg 16:0/20:4(omega-6);1-hexadecanoyl-2-(5z,8z,11z,14z)-eicosatetraenoyl-sn-glycerol;1-hexadecanoyl-2-(5z,8z,11z,14z)-icosatetraenoyl-sn-glycerol;1-hexadecanoyl-2-(5z,8z,11z,14z-eicosatetraenoyl)-sn-glycerol;Dag(16:0/20:4omega6);Dg(16:0/20:4(5z,8z,11z,14z)/0:0);Dg(16:0/20:4/0:0);Dg(16:0/20:4omega6);Diacylglycerol(16:0/20:4omega6);(2s)-1-hydroxy-3-(palmitoyloxy)propan-2-yl (5z,8z,11z,14z)-icosa-5,8,11,14-tetraenoic acid
PW_C003163
DG36:4
16217
49
83621
331
97420
383
113465
8
114710
390
116929
398
353
Calcium
HMDB0000464
Calcium is essential for the normal growth and maintenance of bones and teeth, and calcium requirements must be met throughout life. Requirements are greatest during periods of growth, such as childhood, during pregnancy and when breast-feeding. Long-term calcium deficiency can lead to osteoporosis, in which the bone deteriorates and there is an increased risk of fractures. Adults need between 1,000 and 1,300 mg of calcium in their daily diet. Calcium is essential for living organisms, particularly in cell physiology, and is the most common metal in many animals. Physiologically, it exists as an ion in the body. Calcium combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Calcium is an important component of a healthy diet. A deficit can affect bone and tooth formation, while overretention can cause kidney stones. Vitamin D is needed to absorb calcium. Dairy products, such as milk and cheese, are a well-known source of calcium. However, some individuals are allergic to dairy products and even more people, particularly those of non-European descent, are lactose-intolerant, leaving them unable to consume dairy products. Fortunately, many other good sources of calcium exist. These include: seaweeds such as kelp, wakame and hijiki; nuts and seeds (like almonds and sesame); beans; amaranth; collard greens; okra; rutabaga; broccoli; kale; and fortified products such as orange juice and soy milk. Calcium has also been found to assist in the production of lymphatic fluids.
14127-61-8
C00076
271
29108
CA%2b2
266
DB01373
[Ca++]
Ca
InChI=1S/Ca/q+2
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
calcium(2+) ion
40.078
39.962591155
0
calcium(2+) ion
2
2
FDB003513
Ca;Calcium element;Ca(2+);Ca2+;Calcium ion;Calcium, doubly charged positive ion
PW_C000353
Ca2+
276
16
303
8
553
14
601
2
941
15
993
21
997
35
1046
3
1163
46
1164
47
1478
49
1491
42
1552
43
2116
58
2138
17
2796
18
2937
9
3159
71
3160
72
3942
29
4186
66
4782
10
4822
28
5340
111
5780
101
7179
205
7232
211
7258
160
7281
190
11774
213
11837
198
11842
210
12198
164
12215
285
15288
151
15350
308
69336
1
77389
331
77600
115
78154
132
78266
356
78526
345
78724
130
78908
114
80413
74
80589
228
81826
51
120220
122
120465
405
121049
124
121300
418
121377
419
121850
383
121923
125
122370
409
122895
135
123099
376
123613
118
123870
454
123936
455
124403
398
124476
136
124924
137
125571
297
125711
478
125981
489
126009
299
126050
490
126533
495
127203
209
127434
506
127460
388
127502
507
128105
390
174
Succinic acid
HMDB0000254
Succinic acid is a dicarboxylic acid. The anion, succinate, is a component of the citric acid cycle capable of donating electrons to the electron transfer chain. Succinate dehydrogenase (SDH) plays an important role in the mitochondria, being both part of the respiratory chain and the Krebs cycle. SDH with a covalently attached FAD prosthetic group, binds enzyme substrates (succinate and fumarate) and physiological regulators (oxaloacetate and ATP). Oxidizing succinate links SDH to the fast-cycling Krebs cycle portion where it participates in the breakdown of acetyl-CoA throughout the whole Krebs cycle. The succinate can readily be imported into the mitochondrial matrix by the n-butylmalonate- (or phenylsuccinate-) sensitive dicarboxylate carrier in exchange with inorganic phosphate or another organic acid, e. g. malate. (PMID 16143825) Mutations in the four genes encoding the subunits of the mitochondrial respiratory chain succinate dehydrogenase are associated with a wide spectrum of clinical presentations (i.e.: Huntington's disease. (PMID 11803021).
110-15-6
C00042
1110
15741
SUC
1078
DB00139
OC(=O)CCC(O)=O
C4H6O4
InChI=1S/C4H6O4/c5-3(6)1-2-4(7)8/h1-2H2,(H,5,6)(H,7,8)
KDYFGRWQOYBRFD-UHFFFAOYSA-N
butanedioic acid
118.088
118.02660868
0.25
2
succinic acid
0
-2
FDB001931
1,2-ethanedicarboxylate;1,2-ethanedicarboxylic acid;1,4-butanedioate;1,4-butanedioic acid;Amber acid;Asuccin;Dihydrofumarate;Dihydrofumaric acid;Katasuccin;Succinate;Wormwood acid;Acide butanedioique;Acide succinique;Acidum succinicum;Bernsteinsaeure;Butandisaeure;Butanedionic acid;E363;Ethylenesuccinic acid;Hooc-ch2-ch2-cooh;Spirit of amber;Butanedionate;Ethylenesuccinate
PW_C000174
Succini
152
3
239
4
502
18
507
8
676
31
1265
5
4255
17
5383
103
6042
155
6102
161
6454
107
6455
108
6489
178
6764
117
6836
166
7362
163
7455
219
7456
220
7477
222
11866
198
12142
151
13259
223
42368
318
42369
315
42402
322
77143
133
77213
134
77483
111
77738
112
77749
129
78426
334
80024
368
80721
119
112846
308
113428
1
119984
406
120192
407
120385
122
120555
414
120990
408
122565
384
122767
120
123029
135
123189
450
123555
374
125138
121
125364
479
125549
481
125930
482
126713
480
126906
501
127082
206
127389
502
128304
391
423
Magnesium
HMDB0000547
Magnesium salts are essential in nutrition, being required for the activity of many enzymes, especially those concerned with oxidative phosphorylation. Physiologically, it exists as an ion in the body. It is a component of both intra- and extracellular fluids and is excreted in the urine and feces. Deficiency causes irritability of the nervous system with tetany, vasodilatation, convulsions, tremors, depression, and psychotic behavior. Magnesium ion in large amounts is an ionic laxative, and magnesium sulfate (Epsom salts) is sometimes used for this purpose. So-called "milk of magnesia" is a water suspension of one of the few insoluble magnesium compounds, magnesium hydroxide; the undissolved particles give rise to its appearance and name. Milk of magnesia is a mild base, and is commonly used as an antacid.
22537-22-0
C00305
888
18420
13-HYDROXY-MAGNESIUM-PROTOPORP
865
DB01378
[Mg++]
Mg
InChI=1S/Mg/q+2
JLVVSXFLKOJNIY-UHFFFAOYSA-N
magnesium(2+) ion
24.305
23.985041898
0
magnesium(2+) ion
2
2
FDB003518
Magnesium;Magnesium ions;Magnesium ion;Magnesium, doubly charged positive ion;Magnesium, ion (mg(2+));Mg(2+);Mg2+
PW_C000423
Mg2+
86
8
227
4
268
16
476
2
727
26
811
5
819
18
883
22
936
39
983
3
992
21
1167
46
1483
49
1529
43
1764
14
2124
10
2411
59
2942
23
3126
29
3373
7
4540
31
4774
91
4869
54
4974
56
5253
104
5329
111
5356
112
5376
103
5906
147
5934
151
6038
155
6094
161
6250
166
6484
178
6594
164
6881
160
6979
199
7170
205
7194
206
7227
213
7233
211
7250
214
7310
216
7313
198
7473
222
11763
132
11843
210
12312
225
12324
249
12513
288
12581
226
12729
290
15275
285
15337
308
77137
133
77236
329
77937
336
78393
334
78417
335
78489
115
78522
331
78536
356
78574
130
80020
368
80045
184
80048
372
80623
118
80654
135
80865
15
80965
253
81841
51
93832
383
94900
27
108596
223
110559
390
115687
398
119974
406
120070
122
120247
382
120702
407
120981
408
121181
124
121265
429
121319
419
121924
125
122086
405
122408
422
122759
120
122921
399
123307
119
123546
374
123835
464
123889
455
124477
136
124637
376
124978
375
125447
297
125598
484
125669
479
125777
481
125921
482
125947
299
125973
495
126000
490
126243
478
126553
491
126753
300
127125
389
127164
501
127380
502
127407
388
127451
507
127804
209
128125
508
128347
395
1799
Heme
HMDB0003178
Heme is the color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic subunit; these are known as hemoproteins.
14875-96-8
C00032
17627
HEME_A
24604415
DB02577
CC1=C(CCC(O)=O)C2=CC3=[N+]4C(=CC5=C(C)C(C=C)=C6C=C7C(C)=C(C=C)C8=[N+]7[Fe--]4(N2C1=C8)N56)C(C)=C3CCC(O)=O
C34H32FeN4O4
InChI=1S/C34H34N4O4.Fe/c1-7-21-17(3)25-13-26-19(5)23(9-11-33(39)40)31(37-26)16-32-24(10-12-34(41)42)20(6)28(38-32)15-30-22(8-2)18(4)27(36-30)14-29(21)35-25;/h7-8,13-16H,1-2,9-12H2,3-6H3,(H4,35,36,37,38,39,40,41,42);/q;+2/p-2/b25-13-,26-13-,27-14-,28-15-,29-14-,30-15-,31-16-,32-16-;
KABFMIBPWCXCRK-RGGAHWMASA-L
4,20-bis(2-carboxyethyl)-10,15-diethenyl-5,9,14,19-tetramethyl-2lambda5,22,23lambda5,25-tetraaza-1-ferraoctacyclo[11.9.1.1^{1,8}.1^{3,21}.0^{2,6}.0^{16,23}.0^{18,22}.0^{11,25}]pentacosa-2,4,6,8,10,12,14,16(23),17,19,21(24)-undecaene-2,23-bis(ylium)-1,1-diuide
616.487
616.177297665
-5.48
2
4,20-bis(2-carboxyethyl)-10,15-diethenyl-5,9,14,19-tetramethyl-2lambda5,22,23lambda5,25-tetraaza-1-ferraoctacyclo[11.9.1.1^{1,8}.1^{3,21}.0^{2,6}.0^{16,23}.0^{18,22}.0^{11,25}]pentacosa-2,4,6,8,10,12,14,16(23),17,19,21(24)-undecaene-2,23-bis(ylium)-1,1-diuide
0
-2
FDB016272
(protoporphyrinato)iron;Ferroheme;Ferroheme b;Ferroprotoheme;Ferroprotoporphyrin;Ferroprotoporphyrin ix;Ferrous protoheme;Ferrous protoheme ix;Haem;Hem;Heme;Iron protoporphyrin;Iron protoporphyrin ix;Iron(ii) protoporphyrin ix;Protoferroheme;Protohaem;Protoheme;Protoheme ix;Reduced hematin
PW_C001799
Heme
247
16
308
10
324
8
608
2
766
5
1244
3
1354
49
1413
36
1963
18
2806
29
2938
9
3238
11
3367
26
3421
14
3734
4
4043
31
4823
28
5170
95
5472
123
5485
125
5517
129
5830
141
6246
78
6283
1
6597
151
7044
160
7060
161
7326
213
11835
198
11898
211
12065
164
13009
298
13021
300
42278
17
76915
293
76931
249
77351
111
77364
130
77367
331
77398
332
77517
115
77629
336
77813
334
78380
133
78602
132
78963
112
79932
134
120431
405
120603
408
120955
407
121085
383
121658
429
121746
124
121910
122
122570
406
122691
384
123065
376
123133
447
123144
136
123228
374
123521
119
123650
398
124216
464
124297
118
124463
135
125142
120
125277
121
125742
482
125896
481
126196
299
126499
297
126512
495
126718
479
126827
480
127224
502
127357
206
127632
388
128070
205
128083
395
128086
390
128309
501
128434
391
964
FAD
HMDB0001248
FAD, also known as flavitan or adeflavin, belongs to the class of organic compounds known as flavin nucleotides. These are nucleotides containing a flavin moiety. Flavin is a compound that contains the tricyclic isoalloxazine ring system, which bears 2 oxo groups at the 2- and 4-positions. FAD is a drug which is used to treat eye diseases caused by vitamin b2 deficiency, such as keratitis and blepharitis. FAD is slightly soluble (in water) and a moderately acidic compound (based on its pKa). FAD has been found in human liver and muscle tissues, and has also been detected in multiple biofluids, such as feces and blood. Within the cell, FAD is primarily located in the cytoplasm, mitochondria, endoplasmic reticulum and peroxisome. FAD exists in all living organisms, ranging from bacteria to humans. In humans, FAD is involved in the risedronate action pathway, the ibandronate action pathway, the valine, leucine and isoleucine degradation pathway, and the pyrimidine metabolism pathway. FAD is also involved in several metabolic disorders, some of which include the oncogenic action OF L-2-hydroxyglutarate in hydroxygluaricaciduria pathway, gaba-transaminase deficiency, 4-hydroxybutyric aciduria/succinic semialdehyde dehydrogenase deficiency, and the saccharopinuria/hyperlysinemia II pathway. FAD is a condensation product of riboflavin and adenosine diphosphate. The coenzyme of various aerobic dehydrogenases, e.g., D-amino acid oxidase and L-amino acid oxidase. (Lehninger, Principles of Biochemistry, 1982, p972).
146-14-5
C00016
643975
16238
FAD
559059
DB03147
CC1=CC2=C(C=C1C)N(C[C@H](O)[C@H](O)[C@H](O)CO[P@](O)(=O)O[P@@](O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC3=C1N=CN=C3N)C1=NC(=O)NC(=O)C1=N2
C27H33N9O15P2
InChI=1S/C27H33N9O15P2/c1-10-3-12-13(4-11(10)2)35(24-18(32-12)25(42)34-27(43)33-24)5-14(37)19(39)15(38)6-48-52(44,45)51-53(46,47)49-7-16-20(40)21(41)26(50-16)36-9-31-17-22(28)29-8-30-23(17)36/h3-4,8-9,14-16,19-21,26,37-41H,5-7H2,1-2H3,(H,44,45)(H,46,47)(H2,28,29,30)(H,34,42,43)/t14-,15+,16+,19-,20+,21+,26+/m0/s1
VWWQXMAJTJZDQX-UYBVJOGSSA-N
{[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}[({[(2R,3S,4S)-5-{7,8-dimethyl-2,4-dioxo-2H,3H,4H,10H-benzo[g]pteridin-10-yl}-2,3,4-trihydroxypentyl]oxy}(hydroxy)phosphoryl)oxy]phosphinic acid
785.5497
785.157134455
-2.27
9
flavine-adenine dinucleotide
0
-3
FDB022511
1h-purin-6-amine flavin dinucleotide;1h-purin-6-amine flavine dinucleotide;Adenine-flavin dinucleotide;Adenine-flavine dinucleotide;Adenine-riboflavin dinuceotide;Adenine-riboflavin dinucleotide;Adenine-riboflavine dinucleotide;Fad;Flamitajin b;Flanin f;Flavin adenine dinucleotide;Flavin adenine dinucleotide oxidized;Flavin-adenine dinucleotide;Flavine adenosine diphosphate;Flavine-adenine dinucleotide;Flavitan;Flaziren;Isoalloxazine-adenine dinucleotide;Riboflavin 5'-adenosine diphosphate;Riboflavin-adenine dinucleotide;Riboflavine-adenine dinucleotide;Adeflavin
PW_C000964
FAD
99
9
114
5
186
8
192
3
216
4
253
17
628
28
825
18
840
2
1188
14
1489
42
1612
29
1622
49
2133
58
2536
22
3723
26
4602
36
4688
31
4741
13
4758
10
4881
6
5268
103
5285
102
5335
111
5496
126
5511
127
5613
118
6030
155
6054
156
6082
161
6116
162
6390
1
6475
178
6499
179
6666
107
7039
163
7175
205
7321
213
7465
222
7487
223
9076
224
11818
216
11887
215
11899
211
12296
225
12328
249
12443
151
12519
227
12595
226
12710
291
12720
292
13029
301
13041
302
43623
318
77080
293
77126
133
77152
134
77501
113
77507
112
77518
115
77541
334
77615
132
77726
337
78054
329
78375
345
78930
331
79222
336
79272
358
80012
368
80034
369
80714
119
119958
406
119999
384
120051
408
120107
407
120432
405
120453
122
120490
124
121278
429
121298
418
121417
382
121489
383
122748
120
122776
121
122802
374
122823
443
123066
376
123087
135
123166
448
123849
464
123868
454
123976
399
124047
398
125348
479
125378
480
125429
482
125474
481
125697
297
125979
489
126107
299
126277
484
126891
501
126920
391
126968
502
126987
207
127011
206
127310
209
127432
506
127602
388
127840
389
1170
Flavin Mononucleotide
HMDB0001520
Flavin mononucleotide (FMN), or riboflavin-5?-phosphate, is a biomolecule produced from riboflavin (vitamin B2) by the enzyme riboflavin kinase and functions as prosthetic group of various oxidoreductases including NADH dehydrogenase as well as cofactor in biological blue-light photo receptors. During the catalytic cycle, the reversible interconversion of oxidized (FMN), semiquinone (FMNH) and reduced (FMNH2) forms occurs in the various oxidoreductases. FMN is a stronger oxidizing agent than NAD and is particularly useful because it can take part in both one- and two-electron transfers. Flavin mononucleotide is also used as an orange-red food colour additive. It is the principal form in which riboflavin is found in cells and tissues.
146-17-8
C00061
643976
17621
FMN
559060
DB03247
CC1=CC2=C(C=C1C)N(C[C@H](O)[C@H](O)[C@H](O)COP(O)(O)=O)C1=NC(=O)NC(=O)C1=N2
C17H21N4O9P
InChI=1S/C17H21N4O9P/c1-7-3-9-10(4-8(7)2)21(15-13(18-9)16(25)20-17(26)19-15)5-11(22)14(24)12(23)6-30-31(27,28)29/h3-4,11-12,14,22-24H,5-6H2,1-2H3,(H,20,25,26)(H2,27,28,29)/t11-,12+,14-/m0/s1
FVTCRASFADXXNN-SCRDCRAPSA-N
{[(2R,3S,4S)-5-{7,8-dimethyl-2,4-dioxo-2H,3H,4H,10H-benzo[g]pteridin-10-yl}-2,3,4-trihydroxypentyl]oxy}phosphonic acid
456.3438
456.104614802
-2.83
6
riboflavin 5'-phosphate
0
-3
FDB001984
Fmn;Flanin;Flavine mononucleotide;Flavol;Riboflavin;Riboflavin 5'-monophosphate;Riboflavin 5'-phosphate;Riboflavin mononucleotide;Riboflavin monophosphate;Riboflavin phosphate;Riboflavin-5'-phosphate na;Riboflavin-5-phosphate;Riboflavine 5'-monophosphate;Riboflavine 5'-phosphate;Riboflavine dihydrogen phosphate;Riboflavine monophosphate;Riboflavine phosphate;Riboflavine-5'-phosphate;Vitamin b2 phosphate;Flavin mononucleotide;Riboflavin 5'-(dihydrogen phosphate)
PW_C001170
FlvnMnt
539
8
1190
14
1692
2
4961
31
5772
101
11900
211
12313
225
77519
115
77590
111
78730
132
120433
405
120454
122
121929
124
123067
376
123088
135
124482
118
125698
297
126104
299
127190
205
127312
209
127686
388
19
Tetrahydrobiopterin
HMDB0000027
Tetrahydrobiopterin or BH4 is a cofactor in the synthesis of nitric oxide. In fact it is used by all three human nitric-oxide synthases (NOS) eNOS, nNOS, and iNOS as well as the enzyme glyceryl-ether monooxygenase. It is also essential in the conversion of phenylalanine to tyrosine by the enzyme phenylalanine-4-hydroxylase; the conversion of tyrosine to L-dopa by the enzyme tyrosine hydroxylase; and conversion of tryptophan to 5-hydroxytryptophan via tryptophan hydroxylase. Specifically, tetrahydrobiopterin is a cofactor for tryptophan 5-hydroxylase 1, tyrosine 3-monooxygenase, and phenylalanine hydroxylase all of which are essential for the formation of the neurotransmitters dopamine, noradrenaline and adrenaline. Tetrahydrobiopterin has been proposed to be involved in promotion of neurotransmitter release in the brain and the regulation of human melanogenesis. A defect in BH4 production and/or a defect in the enzyme dihydropteridine reductase (DHPR) causes phenylketonuria type IV, as well as dopa-responsive dystonias. BH4 is also implicated in Parkinson's disease, Alzheimer's disease and depression. Tetrahydrobiopterin is present in probably every cell or tissue of higher animals. On the other hand, most bacteria, fungi and plants do not synthesize tetrahydrobiopterin. -- Wikipedia.
17528-72-2
C00272
1125
15372
TETRA-H-BIOPTERIN
1093
DB00360
CC(O)C(O)C1CNC2=C(N1)C(=O)N=C(N)N2
C9H15N5O3
InChI=1S/C9H15N5O3/c1-3(15)6(16)4-2-11-7-5(12-4)8(17)14-9(10)13-7/h3-4,6,12,15-16H,2H2,1H3,(H4,10,11,13,14,17)
FNKQXYHWGSIFBK-UHFFFAOYSA-N
2-amino-6-(1,2-dihydroxypropyl)-1,4,5,6,7,8-hexahydropteridin-4-one
241.2471
241.117489371
-2.04
6
tetrahydrobiopterin
0
0
FDB021880
(1r,2s)-(2-amino-3,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)-1,2-propandiol;2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydoro-4(1h)-5,6,7,8-tetrahydro-2-amino-6-(1,2-dihydroxypropyl)-4(1h)-pteridinone;2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(1h)-pteridinone;5,6,7,8-erythro-tetrahydrobiopterin;5,6,7,8-tetra-h-biopterin;5,6,7,8-tetrahydro-2-amino-6-(1,2-dihydroxypropyl)-4(1h)-pteridinone;5,6,7,8-tetrahydrobiopterin;L-erythro-2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(3h)-pteridinon;Tetra-h-biopterin;Tetra-hydro-biopterin;Tetrahydrobiopterin;2-amino-6-(1,2-dihydroxypropyl)-5,6,7,8-tetrahydoro-4(1h)-pteridinone;Bh4
PW_C000019
BH4
1957
2
4085
8
4800
14
4803
14
4962
31
11901
211
77520
115
78663
132
120434
405
121616
124
123068
376
124174
118
126493
299
127585
388
1867
Nitric oxide
HMDB0003378
The biologically active molecule nitric oxide (NO) is a simple, membrane-permeable gas with unique chemistry. It is formed by the conversion of L-arginine to L-citrulline, with the release of NO. The enzymatic oxidation of L-arginine to L-citrulline takes place in the presence of oxygen and NADPH using flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), heme, thiol, and tetrahydrobiopterin as cofactors. The enzyme responsible for the generation of NO is nitric oxide synthase (E.C. 1.7.99.7; NOS). Three NOS isoforms have been described and shown to be encoded on three distinct genes: neuronal NOS (nNOS, NOS type I), inducible NOS (NOS type II), and endothelial NOS (eNOS, NOS type III). Two of them are constitutively expressed and dependent on the presence of calcium ions and calmodulin to function (nNOS and eNOS), while iNOS is considered non-constitutive and calcium-independent. However, experience has shown that constitutive expression of nNOS and eNOS is not as rigid as previously thought (i.e. either present or absent), but can be dynamically controlled during development and in response to injury. Functionally, NO may act as a hormone, neurotransmitter, paracrine messenger, mediator, cytoprotective molecule, and cytotoxic molecule. NO has multiple cellular molecular targets. It influences the activity of transcription factors, modulates upstream signaling cascades, mRNA stability and translation, and processes the primary gene products. In the brain, many processes are linked to NO. NO activates its receptor, soluble guanylate cyclase by binding to it. The stimulation of this enzyme leads to increased synthesis of the second messenger, cGMP, which in turn activates cGMP-dependent kinases in target cells. NO exerts a strong influence on glutamatergic neurotransmission by directly interacting with the N-methyl-D-aspartate (NMDA) receptor. Neuronal NOS is connected to NMDA receptors (see below) and sharply increases NO production following activation of this receptor. Thus, the level of endogenously produced NO around NMDA synapses reflects the activity of glutamate-mediated neurotransmission. However, there is recent evidence showing that non-NMDA glutamate receptors (i.e. AMPA and type I metabotropic receptors) also contribute to NO generation. Besides its influence on glutamate, NO is known to have effects on the storage, uptake and/or release of most other neurotransmitters in the CNS (acetylcholine, dopamine, noradrenaline, GABA, taurine, and glycine) as well as of certain neuropeptides. Finally, since NO is a highly diffusible molecule, it may reach extrasynaptic receptors at target cell membranes that are some distance away from the place of NO synthesis. NO is thus capable of mediating both synaptic and nonsynaptic communication processes. NO is a potent vasodilator (a major endogenous regulator of vascular tone), and an important endothelium-dependent relaxing factor. NO is synthesized by NO synthases (NOS) and NOS are inhibited by asymmetrical dimethylarginine (ADMA). ADMA is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) and excreted in the kidneys. Lower ADMA levels in pregnant women compared to non-pregnant controls suggest that ADMA has a role in vascular dilatation and blood pressure changes. Several studies show an increase in ADMA levels in pregnancies complicated with preeclampsia. Elevated ADMA levels in preeclampsia are seen before clinical symptoms have developed; these findings suggest that ADMA has a role in the pathogenesis of preeclampsia. In some pulmonary hypertensive states such as ARDS, the production of endogenous NO may be impaired. Nitric oxide inhalation selectively dilates the pulmonary circulation. Significant systemic vasodilation does not occur because NO is inactivated by rapidly binding to hemoglobin. In an injured lung with pulmonary hypertension, inhaled NO produces local vasodilation of well-ventilated lung units and may "steal" blood flow away from unventilated regions. This reduces intrapulmonary shunting and may improve systemic arterial oxygenation. Nitric oxide is a chemical mediator fundamental in the maintenance of adequate tissue perfusion and effective cardiovascular function. The use of nitrates is well established as pharmacological agents but it is only recently that it has been recognized that they act as a source of nitric oxide (PMID: 16966108, 8752507, 17181668, 16005189). Nitric oxide is used as a food additive (EAFUS: Everything Added to Food in the United States).
10102-43-9
C00533
145068
16480
NITRIC-OXIDE
127983
DB00435
[N]=O
NO
InChI=1S/NO/c1-2
MWUXSHHQAYIFBG-UHFFFAOYSA-N
nitroso
30.0061
29.997988627
0
nitric oxide
0
0
FDB021825
Mononitrogen monoxide;Nitric oxide;Nitrogen monoxide;Nitrogen oxide;Nitrogen protoxide;Nitrosyl hydride;Nitrosyl radical;Nitroxide radical;Nitroxyl;(no)(.);[no];Edrf;Endothelium-derived relaxing factor;Monoxido de nitrogeno;Monoxyde d'azote;Nitrogen monooxide;Nitrosyl;No;(.)no;No(.);Oxido de nitrogeno(ii);Oxido nitrico;Oxyde azotique;Oxyde nitrique;Stickstoff(ii)-oxid;Stickstoffmonoxid
PW_C001867
NO
4795
14
4799
14
11896
211
77514
115
80331
8
120428
405
123062
376
949
Prostaglandin E2
HMDB0001220
The naturally occurring prostaglandin E2 (PGE2) is known in medicine as dinoprostone, and it is the most common and most biologically active of the mammalian prostaglandins. It has important effects during labour and also stimulates osteoblasts to release factors which stimulate bone resorption by osteoclasts (a type of bone cell that removes bone tissue by removing the bone's mineralized matrix). PGE2 is also the prostaglandin that ultimately induces fever. PGE2 has been shown to increase vasodilation and cAMP production, enhance the effects of bradykinin and histamine, and induce uterine contractions and platelet aggregation. PGE2 is also responsible for maintaining the open passageway of the fetal ductus arteriosus, decreasing T-cell proliferation and lymphocyte migration, and activating the secretion of IL-1α and IL-2. PGE2 exhibits both pro- and anti-inflammatory effects, particularly on dendritic cells (DC). Depending on the nature of maturation signals, PGE2 has different and sometimes opposite effects on DC biology. PGE2 exerts an inhibitory action, reducing the maturation of DC and their ability to present antigen. PGE2 has also been shown to stimulate DC and promote IL-12 production when given in combination with TNF-alpha. PGE2 is an environmentally bioactive substance. Its action is prolonged and sustained by other factors especially IL-10. It modulates the activities of professional DC by acting on their differentiation, maturation, and their ability to secrete cytokines. PGE2 is a potent inducer of IL-10 in bone marrow-derived DC (BM-DC). PGE2-induced IL-10 is a key regulator of the BM-DC pro-inflammatory phenotype (PMID: 16978535). Prostaglandins are eicosanoids. The eicosanoids consist of the prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and lipoxins (LXs). The PGs and TXs are collectively identified as prostanoids. Prostaglandins were originally shown to be synthesized in the prostate gland, thromboxanes from platelets (thrombocytes), and leukotrienes from leukocytes, hence the derivation of their names. All mammalian cells except erythrocytes synthesize eicosanoids. These molecules are extremely potent and are able to cause profound physiological effects at very dilute concentrations. All eicosanoids function locally at the site of synthesis through receptor-mediated G-protein linked signalling pathways.
363-24-6
C00584
5280360
15551
5Z13E-15S-1115-DIHYDROXY-9-OXOPROS
4444059
DB00917
CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O
C20H32O5
InChI=1S/C20H32O5/c1-2-3-6-9-15(21)12-13-17-16(18(22)14-19(17)23)10-7-4-5-8-11-20(24)25/h4,7,12-13,15-17,19,21,23H,2-3,5-6,8-11,14H2,1H3,(H,24,25)/b7-4-,13-12+/t15-,16+,17+,19+/m0/s1
XEYBRNLFEZDVAW-ARSRFYASSA-N
(5Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-5-oxocyclopentyl]hept-5-enoic acid
352.4651
352.224974134
-3.90
3
dinoprostone
0
-1
FDB022498
(-)-prostaglandin e2;(5z,13e)-(15s)-11alpha,15-dihydroxy-9-oxoprost-13-enoate;(5z,13e)-(15s)-11alpha,15-dihydroxy-9-oxoprost-13-enoic acid;(5z,13e)-(15s)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate;(5z,13e)-(15s)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoic acid;(5z,13e,15s)-11-alpha,15-dihydroxy-9-oxoprost-5,13-dienoate;(5z,13e,15s)-11-alpha,15-dihydroxy-9-oxoprost-5,13-dienoic acid;5-trans-pge2;Dinoprostone;Dinoprostonum;Glandin;L-prostaglandin e2;Minprositin e2;Minprostin e2;Pge2;Prepidil;Prostaglandin e;Prostaglandin e2;Prostaglandin e2alpha;Prostarmon e;Prostin;Prostin e2;(15s)-prostaglandin e2;(5z,11alpha,13e,15s)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid;(e,z)-(1r,2r,3r)-7-(3-hydroxy-2-((3s)-(3-hydroxy-1-octenyl))-5-oxocyclopentyl)-5-heptenoic acid;(z)-7-((1r,2r,3r)-3-hydroxy-2-((s,e)-3-hydroxyoct-1-enyl)-5-oxocyclopentyl)hept-5-enoic acid;Dinoproston;Dinoprostona;Propess;(5z,11a,13e,15s)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oate;(5z,11a,13e,15s)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid;(5z,11alpha,13e,15s)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oate;(5z,11α,13e,15s)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oate;(5z,11α,13e,15s)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid;(5z,13e)-(15s)-11a,15-dihydroxy-9-oxoprost-13-enoate;(5z,13e)-(15s)-11a,15-dihydroxy-9-oxoprost-13-enoic acid;(5z,13e)-(15s)-11α,15-dihydroxy-9-oxoprost-13-enoate;(5z,13e)-(15s)-11α,15-dihydroxy-9-oxoprost-13-enoic acid;(5z,13e)-(15s)-11a,15-dihydroxy-9-oxoprosta-5,13-dienoate;(5z,13e)-(15s)-11a,15-dihydroxy-9-oxoprosta-5,13-dienoic acid;(5z,13e)-(15s)-11α,15-dihydroxy-9-oxoprosta-5,13-dienoate;(5z,13e)-(15s)-11α,15-dihydroxy-9-oxoprosta-5,13-dienoic acid;(e,z)-(1r,2r,3r)-7-(3-hydroxy-2-((3s)-(3-hydroxy-1-octenyl))-5-oxocyclopentyl)-5-heptenoate;(z)-7-((1r,2r,3r)-3-hydroxy-2-((s,e)-3-hydroxyoct-1-enyl)-5-oxocyclopentyl)hept-5-enoate
PW_C000949
PGE2
613
2
1361
49
77423
331
115883
8
121092
383
123657
398
216
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1
Q9NQ66
The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.
HMDBP00222
PLCB1
20p12
AL050315
1
3.1.4.11
2576
14
2790
46
11646
89
69337
1
80090
308
80230
8
136124
653
136191
665
136199
66
14793
Succinate receptor 1
Q9BXA5
Receptor for succinate.
SUCNR1
1
112844
14
112847
308
113429
1
113471
8
1248
Mitogen-activated protein kinase 11
Q15759
Kinase involved in a signal transduction pathway that is activated by changes in the osmolarity of the extracellular environment, by cytokines, or by environmental stress. Phosphorylates preferentially transcription factor ATF2
HMDBP01336
MAPK11
22q13.33
AL022328
1
2.7.11.24
4118
2
115815
8
872
Nitric oxide synthase, endothelial
P29474
Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.
Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.
HMDBP00929
NOS3
7q36
L10707
1
1.14.13.39
4086
8
4963
31
1108
Protein kinase C alpha type
P17252
PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. PKC also serves as the receptor for phorbol esters, a class of tumor promoters
HMDBP01180
PRKCA
17q22-q23.2
X52479
1
2.7.11.13
4224
2
80281
8
136200
66
1184
Mitogen-activated protein kinase 3
P27361
Involved in both the initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors such as ELK-1. Phosphorylates EIF4EBP1; required for initiation of translation. Phosphorylates microtubule-associated protein 2 (MAP2). Phosphorylates SPZ1. Phosphorylates heat shock factor protein 4 (HSF4)
HMDBP01263
MAPK3
16p11.2
AC012645
1
2.7.11.24
11659
8
80758
23
1117
Mitogen-activated protein kinase 1
P28482
Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity
HMDBP01190
MAPK1
22q11.2|22q11.21
Z11694
1
2.7.11.24
4038
2
11658
8
80757
23
914
Prostaglandin G/H synthase 1
P23219
May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells.
HMDBP00976
PTGS1
9q32-q33.3
M31813
1
1.14.99.1
248
16
616
2
1392
49
1964
18
3882
9
6247
78
115858
8
1749
Inhibitor of nuclear factor kappa-B kinase subunit alpha
O15111
Acts as part of the IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF- kappa-B complex and ultimately the degradation of the inhibitor. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. Also phosphorylates NCOA3. Phosphorylates 'Ser-10' of histone H3 at NF- kappa-B-regulated promoters during inflammatory responses triggered by cytokines
HMDBP02038
CHUK
10q24-q25
AF080157
1
2.7.11.10
4133
14
80314
8
1222
Inhibitor of nuclear factor kappa-B kinase subunit beta
O14920
Acts as part of the IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF- kappa-B complex and ultimately the degradation of the inhibitor. Also phosphorylates NCOA3
HMDBP01302
IKBKB
8p11.2
AF031416
1
2.7.11.10
4134
14
80140
8
8558
NF-kappa-B essential modulator
Q9Y6K9
Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin seems to play a role in IKK activation by multiple signaling receptor pathways. However, the specific type of polyubiquitin recognized upon cell stimulation (either 'Lys-63'-linked or linear polyubiquitin) and its functional importance is reported conflictingly. Also considered to be a mediator for TAX activation of NF-kappa-B. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination.
IKBKG
1
80355
8
1808
Nuclear factor NF-kappa-B p105 subunit
P19838
NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF- kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF- kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post- translationally. p50 binds to the kappa-B consensus sequence 5'- GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105
HMDBP02145
NFKB1
4q24
BC051765
1
4145
2
4147
23
80356
8
115939
27
1802
Cyclic AMP-responsive element-binding protein 1
P16220
This protein binds the cAMP response element (CRE), a sequence present in many viral and cellular promoters. CREB stimulates transcription on binding to the CRE. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Implicated in synchronization of circadian rhythmicity
HMDBP02133
CREB1
2q34
X55545
1
3857
2
3980
23
115974
27
1140
Phospholipase C, beta 1
1
PW_P001140
1302
216
1
471
353
1
8084
Succinate receptor 1
1
PW_P008084
16271
14793
975
Mitogen-activated protein kinase 11
1
PW_P000975
1101
1248
1
409
423
1
937
Nitric-oxide synthase, endothelial
1
PW_P000937
1062
872
2
379
1799
1
380
964
1
381
1170
1
382
19
1
1142
Protein kinase C
1
PW_P001142
1304
1108
1
7904
ERK1, ERK2
1
PW_P007904
16005
1184
16006
1117
2023
COX1 homodimer complex
1
PW_P002023
3915
914
1
7955
Inhibitor of nuclear factor kappa-B kinase
1
PW_P007955
16091
1749
16092
1222
16093
8558
88976
8
988
Nuclear factor NF-kappa-B p105 subunit
1
PW_P000988
1117
1808
1
984
Inhibitor of nuclear factor kappa-B kinase subunit beta
1
PW_P000984
1110
1222
1
925
Cyclic AMP-responsive element-binding protein 1
1
PW_P000925
1050
1802
1
140796
PW_R140796
Right
523007
6123
1
Compound
false
523008
892
1
Compound
false
523009
3163
1
Compound
false
130870
1140
3.1.4.11
143078
PW_R143078
Right
532132
988
1
ProteinComplex
false
532133
984
1
ProteinComplex
false
532134
988
1
ProteinComplex
false
133147
7955
6542
PW_T006542
6785
988
1
ProteinComplex
8
27
Unknown
973
Activation
PW_I000973
1945
8084
ProteinComplex
1
1946
1140
ProteinComplex
1
964
Activation
PW_I000964
1927
174
Compound
1
1928
8084
ProteinComplex
1
974
Activation
PW_I000974
1947
892
Compound
1
1948
353
Compound
1
975
Activation
PW_I000975
1949
353
Compound
1
1950
975
ProteinComplex
1
976
Activation
PW_I000976
1951
353
Compound
1
1952
937
ProteinComplex
1
977
Activation
PW_I000977
1953
937
ProteinComplex
1
1954
1867
Compound
1
978
Activation
PW_I000978
1955
3163
Compound
1
1956
1142
ProteinComplex
1
979
Activation
PW_I000979
1957
1142
ProteinComplex
1
1958
7904
ProteinComplex
1
980
Activation
PW_I000980
1959
7904
ProteinComplex
1
1960
2023
ProteinComplex
1
981
Activation
PW_I000981
1961
2023
ProteinComplex
1
1962
949
Compound
1
982
Activation
PW_I000982
1963
1142
ProteinComplex
1
1964
7955
ProteinComplex
1
983
Activation
PW_I000983
1965
975
ProteinComplex
1
1966
925
ProteinComplex
1
2051927
6123
8
3
false
247
604
10
regular
100
100
2051928
892
8
3
false
877
594
10
regular
100
120
2051929
3163
8
3
false
877
789
10
regular
100
100
2051930
353
8
9
true
547
476
10
regular
100
25
2052076
174
308
3
false
572
76
10
regular
100
100
2052287
353
8
51
false
1168
614
10
regular
78
78
2088949
423
8
9
false
1426
600
10
regular
100
25
2089023
1799
8
9
true
977
717
10
regular
100
25
2089024
964
8
9
true
977
697
10
regular
100
25
2089025
1170
8
9
true
977
667
10
regular
100
35
2089026
19
8
9
true
977
647
10
regular
100
25
2089054
1867
8
64
false
1168
347
10
regular
78
78
2089912
949
8
3
false
877
1249
10
regular
100
110
729317
216
8
2
false
567
621
8
subunit
regular
150
70
729354
14793
8
80
false
517
216
8
subunit
regular
200
130
739894
1248
8
2
false
1401
615
8
subunit
regular
150
70
739915
872
8
2
false
1132
487
8
subunit
regular
150
70
739947
1108
8
2
false
852
969
8
subunit
regular
150
70
740053
1184
8
2
false
712
1104
8
subunit
regular
150
70
740054
1117
8
2
false
852
1104
8
subunit
regular
150
70
740072
914
8
2
false
1132
1104
8
subunit
regular
150
70
740285
1749
8
2
false
222
969
8
subunit
regular
150
70
740286
1222
8
2
false
362
969
8
subunit
regular
150
70
740287
8558
8
2
false
502
969
8
subunit
regular
150
70
740365
1808
8
2
false
282
789
8
subunit
regular
150
70
740366
1222
8
2
false
447
789
8
subunit
regular
150
70
740367
1808
8
2
false
362
1149
8
subunit
regular
150
70
740425
1808
27
2
false
367
1584
8
subunit
regular
150
70
740567
1802
27
2
false
401
1725
8
subunit
regular
150
70
616348
1140
85408
8
727802
729317
9911
2051930
2788753
Cofactor
616385
8084
85408
8
727839
729354
626924
975
85408
8
738378
739894
9921
2088949
2838267
Cofactor
626946
937
85408
8
738400
739915
9922
2089023
2838368
Cofactor
9923
2089024
2838369
Cofactor
9924
2089025
2838370
Cofactor
9925
2089026
2838371
Cofactor
626978
1142
85408
8
738432
739947
627084
7904
85408
8
738538
740053
738539
740054
627102
2023
85408
8
738557
740072
627313
7955
85408
8
738770
740285
738771
740286
738772
740287
627390
988
85408
8
738849
740365
627391
984
85408
8
738850
740366
627392
988
85408
8
738851
740367
627450
988
85408
27
738909
740425
627583
925
85408
27
739051
740567
2788750
M347 654 C377 654 537 656 567 656
5
false
18
2788751
M877 654 C847 654 747 656 717 656
5
false
18
true
M 758.9468550441649 456.92821279043665 L 744 455.6666564941406 L 750.3808877211858 469.24179081721894
false
2788752
M877 839 C847 839 673 838 643 838 C642 802 642 791 642 691
5
false
18
true
M 758.9468550441649 456.92821279043665 L 744 455.6666564941406 L 750.3808877211858 469.24179081721894
false
2788753
M-53 486 L-53 536 L-3 486 z
10
true
18
2788916
M642 331 C642 361 642 591 642 621
149
false
18
true
M 1570.5 645.7596189432334 L 1578 658.75 L 1585.5 645.7596189432334
false
2788917
M642 621 C642 591 597 434.75 597 404.75
149
true
18
true
M 596.2801680324461 210.26155629629605 L 581.3333129882812 209 L 587.714200709467 222.57513432307834
false
2788950
M622 176 C622 206 622 211 622 241
149
false
18
true
M 1545.5 374.5096189432334 L 1553 387.5 L 1560.5 374.5096189432334
false
2788951
M622 241 C622 211 572 163.5 572 133.5
149
true
18
true
M 596.2801680324461 210.26155629629605 L 581.3333129882812 209 L 587.714200709467 222.57513432307834
false
2789226
M977 654 C1000 655 1142 655 1168 653
149
false
18
true
M 1961.6231060406117 720.4742253874945 L 1974 712 L 1960.4726585573405 705.5184081049707
false
2789227
M1207 614 C1207 584 802 613.5 802 583.5
149
true
18
true
M 1022.9468550441649 210.26155629629605 L 1008 209 L 1014.3808877211858 222.57513432307834
false
2838266
M1246 653 C1276 653 1371 650 1401 650
149
false
18
true
M 2132.0096189432334 719.5 L 2145 712 L 2132.0096189432334 704.5
false
2838267
M1286 610 L1286 660 L1336 610 z
10
true
18
2838268
M1221 465.5 C1191 465.5 1194 458 1164 458
149
true
18
true
M 960.2801680324461 210.26155629629605 L 945.3333129882812 209 L 951.714200709467 222.57513432307834
false
2838367
M1207 614 C1207 596 1206 577 1207 557
149
false
18
true
M 2005.5 834.7596189432334 L 2013 847.75 L 2020.5 834.7596189432334
false
2838368
M972 712 L972 762 L1022 712 z
10
true
18
2838369
M972 692 L972 742 L1022 692 z
10
true
18
2838370
M972 662 L972 712 L1022 662 z
10
true
18
2838371
M972 642 L972 692 L1022 642 z
10
true
18
2838372
M1032 732 C1032 702 1032 623.75 1032 593.75
149
true
18
true
M 1036.2802290676022 518.261556296296 L 1021.3333740234375 517 L 1027.7142617446234 530.5751343230784
false
2838415
M1207 425 C1207 437 1207 473 1207 487
149
false
18
true
M 1285.6134810207272 627.5948692845773 L 1270.6666259765625 626.3333129882812 L 1277.0475136977484 639.9084473113596
false
2838416
M1052 572 C1052 602 1027 827.75 1027 857.75
149
true
18
2838517
M927 889 C927 919 927 939 927 969
149
false
18
true
M 1770.5 942.5096189432334 L 1778 955.5 L 1785.5 942.5096189432334
false
2838518
M927 969 C927 939 797 731.5 797 701.5
149
true
18
true
M 1285.6134810207272 627.5948692845773 L 1270.6666259765625 626.3333129882812 L 1277.0475136977484 639.9084473113596
false
2838999
M927 1039 C927 1069 927 1074 927 1104
149
false
18
true
M 1770.5 1170.0096189432334 L 1778 1183 L 1785.5 1170.0096189432334
false
2839000
M927 1104 C927 1074 797 959 797 929
149
true
18
true
M 830.9468550441649 718.261556296296 L 816 717 L 822.3808877211858 730.5751343230784
false
2839082
M1002 1139 C1017 1139 1117 1139 1132 1139
149
false
18
true
M 1770.5 1390.0096189432334 L 1778 1403 L 1785.5 1390.0096189432334
false
2839083
M1207 1104 C1207 1074 797 1179 797 1149
149
true
18
true
M 830.9468550441649 846.261556296296 L 816 845 L 822.3808877211858 858.5751343230784
false
2839240
M1207 692 C1208 711 1207 1085 1207 1104
149
false
18
true
M 1923.0644009829866 1476.611518094107 L 1938 1478 L 1931.7346610946918 1464.371150877582
false
2839590
M927 1249 C927 1219 927 1204 927 1174
149
false
18
true
M 1181.6134810207272 947.5948692845773 L 1166.6666259765625 946.3333129882812 L 1173.0475136977484 959.9084473113596
false
2839591
M1207 1174 C1207 1204 957 1579 957 1609
149
true
18
2840038
M852 1004 C838 1004 672 1005 652 1004
149
false
18
true
M 1625.5 1150.0096189432334 L 1633 1163 L 1640.5 1150.0096189432334
false
2840039
M577 969 C577 939 792 1014 792 984
149
true
18
true
M 1058.9468550441647 658.261556296296 L 1044 657 L 1050.380887721186 670.5751343230784
false
2840390
M357 859 C397 911 397 921 437 969
5
false
18
2840391
M522 859 C488 907 478 918 437 969
5
false
18
2840392
M437 1149 C437 1119 437 1069 437 1039
5
false
18
true
M 1005.6135420558836 887.5948692845773 L 990.6666870117188 886.3333129882812 L 997.0475747329045 899.9084473113596
false
2840653
M437 1219 C437 1249 442 1554 442 1584
83
false
18
true
M 1410.5 1440.0096189432334 L 1418 1453 L 1425.5 1440.0096189432334
false
2840654
M442 1584 C442 1554 437 1229 437 1199
83
true
18
true
M 1490.5 1970.0096189432334 L 1498 1983 L 1505.5 1970.0096189432334
false
2841246
M1476 685 C1476 715 1482 1729 1482 1759 C1450 1761 588 1758 551 1760
149
false
18
true
M 2314.5 1012.2596189432334 L 2322 1025.25 L 2329.5 1012.2596189432334
false
2841247
M476 1725 C476 1695 1341 801.25 1341 771.25
149
true
18
true
M 932.9468550441649 674.261556296296 L 918 673 L 924.3808877211858 686.5751343230784
false
2846152
M442 1654 C458 1679 639.5 1615 684.5 1599
147
false
18
true
M 1570.5644009829866 2263.611518094107 L 1585.5 2265 L 1579.2346610946918 2251.3711508775823
false
2846195
M476 1725 C485 1684 549.5 1640 675.5 1600
147
false
18
false
false
621328
85408
140796
8
2508363
2051927
2788750
Left
2508364
2051928
2788751
Right
2508365
2051929
2788752
Right
579379
130870
616348
632365
85408
143078
8
11114
627390
2840390
Left
11115
627391
2840391
Left
11116
627392
2840392
Right
590411
133147
627313
48955
6542
85408
167
627392
2840653
Left
168
627450
2840654
Right
2464
973
85408
8
3054
616385
2788916
Left
3055
616348
2788917
Right
2465
964
85408
308
759
2052076
2788950
Left
3056
616385
2788951
Right
2466
974
85408
8
760
2051928
2789226
Left
761
2052287
2789227
Right
2467
975
85408
8
762
2052287
2838266
Left
3057
626924
2838268
Right
2468
976
85408
8
763
2052287
2838367
Left
3058
626946
2838372
Right
2469
977
85408
8
764
2089054
2838415
Right
3059
626946
2838416
Left
2470
978
85408
8
765
2051929
2838517
Left
3060
626978
2838518
Right
2471
979
85408
8
3061
626978
2838999
Left
3062
627084
2839000
Right
2472
980
85408
8
3063
627084
2839082
Left
3064
627102
2839083
Right
2473
981
85408
8
766
2089912
2839590
Right
3065
627102
2839591
Left
2474
982
85408
8
3066
626978
2840038
Left
3067
627313
2840039
Right
2475
983
85408
27
3068
626924
2841246
Left
3069
627583
2841247
Right
63977
2839240
63982
2846152
63983
2846195
140183
261
1312
2.2
2.2
0
2
14
327
267
284971
M126 392 C126 342 176 292 226 292 C620 292 1131 292 1525 292 C1575 292 1625 342 1625 392 C1625 843 1625 1428 1625 1879 C1625 1929 1575 1979 1525 1979 C1131 1979 620 1979 226 1979 C176 1979 126 1929 126 1879 C126 1428 126 843 126 392
1
true
6
1499.0
1687.0
345889
235
DNA Transcription
716
1549
20
1.0
1.0
200
15
345897
235
Nucleus
511
1334
20
1.6
1.6
200
15
345905
235
Cytoplasm
183
328
20
1.6
1.6
200
15
345906
235
Extracellular
1273
153
20
1.6
1.6
200
15