685
Pathway
Phenylalanine Metabolism
The pathways of the metabolism of phenylalaline begins with the conversion of chorismate to prephenate through a P-protein (chorismate mutase:pheA). Prephenate then interacts with a hydrogen ion through the same previous enzyme resulting in a release of carbon dioxide, water and a phenolpyruvic acid. Three enzymes those enconde by tyrB, aspC and ilvE are involved in catalyzing the third step of these pathways, all three can contribute to the synthesis of phenylalanine: only tyrB and aspC contribute to biosynthesis of tyrosine.
Phenolpyruvic acid can also be obtained from a reversivle reaction with ammonia, a reduced acceptor and a D-amino acid dehydrogenase, resulting in a water, an acceptor and a D-phenylalanine, which can be then transported into the periplasmic space by aromatic amino acid exporter.
L-phenylalanine also interacts in two reversible reactions, one involved with oxygen through a catalase peroxidase resulting in a carbon dioxide and 2-phenylacetamide. The other reaction involved an interaction with oxygen through a phenylalanine aminotransferase resulting in a oxoglutaric acid and phenylpyruvic acid.
L-phenylalanine can be imported into the cytoplasm through an aromatic amino acid:H+ symporter AroP.
The compound can also be imported into the periplasmic space through a transporter: L-amino acid efflux transporter.
Metabolic
PW000921
Center
PathwayVisualizationContext1208
2525
2854
#000099
PathwayVisualization669
685
Phenylalanine Metabolism
The pathways of the metabolism of phenylalaline begins with the conversion of chorismate to prephenate through a P-protein (chorismate mutase:pheA). Prephenate then interacts with a hydrogen ion through the same previous enzyme resulting in a release of carbon dioxide, water and a phenolpyruvic acid. Three enzymes those enconde by tyrB, aspC and ilvE are involved in catalyzing the third step of these pathways, all three can contribute to the synthesis of phenylalanine: only tyrB and aspC contribute to biosynthesis of tyrosine.
Phenolpyruvic acid can also be obtained from a reversivle reaction with ammonia, a reduced acceptor and a D-amino acid dehydrogenase, resulting in a water, an acceptor and a D-phenylalanine, which can be then transported into the periplasmic space by aromatic amino acid exporter.
L-phenylalanine also interacts in two reversible reactions, one involved with oxygen through a catalase peroxidase resulting in a carbon dioxide and 2-phenylacetamide. The other reaction involved an interaction with oxygen through a phenylalanine aminotransferase resulting in a oxoglutaric acid and phenylpyruvic acid.
L-phenylalanine can be imported into the cytoplasm through an aromatic amino acid:H+ symporter AroP.
The compound can also be imported into the periplasmic space through a transporter: L-amino acid efflux transporter.
Metabolic
3
109785
571
SubPathway
109294
104
Compound
109795
580
SubPathway
109304
7748
Compound
2318
15983
Gelfand DH, Steinberg RA: Escherichia coli mutants deficient in the aspartate and aromatic amino acid aminotransferases. J Bacteriol. 1977 Apr;130(1):429-40.
685
Pathway
1
Cell
CL:0000000
5
Hepatocyte
CL:0000182
4
Cardiomyocyte
CL:0000746
3
Neuron
CL:0000540
7
Epithelial Cell
CL:0000066
6
Myocyte
CL:0000187
2
Platelet
CL:0000233
3
Escherichia coli
562
Prokaryote
4
Arabidopsis thaliana
3702
Eukaryote
Thale cress
23
Pseudomonas aeruginosa
287
Prokaryote
1
Homo sapiens
9606
Eukaryote
Human
12
Mus musculus
10090
Eukaryote
Mouse
2
Bacteria
2
Prokaryote
Bacteria
24
Solanum lycopersicum
4081
Eukaryote
Tomato
18
Saccharomyces cerevisiae
4932
Eukaryote
Yeast
21
Xenopus laevis
8355
Eukaryote
African clawed frog
6
Caenorhabditis elegans
6239
Eukaryote
Roundworm
25
Escherichia coli (strain K12)
83333
Prokaryote
60
Nitzschia sp.
0001
Eukaryote
Nitzschia4
17
Rattus norvegicus
10116
Eukaryote
Rat
5
Bos taurus
9913
Eukaryote
Cattle
10
Drosophila melanogaster
7227
Eukaryote
Fruit fly
49
Bathymodiolus platifrons
220390
Eukaryote
Deep sea mussel
19
Schizosaccharomyces pombe
4896
Eukaryote
35
Chloroplast
GO:0009507
1
Cytosol
GO:0005829
3
Mitochondrial Matrix
GO:0005759
5
Cytoplasm
GO:0005737
11
Extracellular Space
GO:0005615
2
Mitochondrion
GO:0005739
7
Endoplasmic Reticulum Membrane
GO:0005789
12
Mitochondrial Inner Membrane
GO:0005743
14
Mitochondrial Outer Membrane
GO:0005741
24
Mitochondrial Intermembrane Space
GO:0005758
13
Endoplasmic Reticulum
GO:0005783
31
Periplasmic Space
GO:0005620
4
Peroxisome
GO:0005777
10
Cell Membrane
GO:0005886
36
Membrane
GO:0016020
53
Endoplasmic Reticulum Body
GO:0010168
34
Plant-Type Vacuole
GO:0000325
32
Inner Membrane
GO:0070258
25
Golgi apparatus
GO:0005794
6
Lysosome
GO:0005764
16
Lysosomal Lumen
GO:0043202
18
Melanosome Membrane
GO:0033162
20
Endoplasmic Reticulum Lumen
GO:0005788
21
Synapse
GO:0045202
15
Nucleus
GO:0005634
40
Periplasm
GO:0042597
1
Liver
BTO:0000759
72
9
28
Stomach
BTO:0001307
155
26
8
Blood Vessel
BTO:0001102
74
11
4
Adrenal Medulla
BTO:0000049
71
8
25
Intestine
BTO:0000648
7
Nervous System
BTO:0001484
11
Heart
BTO:0000562
73
10
9
Muscle
BTO:0000887
141
18
24
Brain
BTO:0000142
89
16
2
Endothelium
BTO:0000393
3
Sympathetic Nervous System
BTO:0001832
94
3
PW_BS000094
225
35
4
1
PW_BS000024
151
1
4
1
PW_BS000151
313
23
PW_BS000024
4
3
1
1
PW_BS000004
8
5
1
1
PW_BS000008
15
11
1
PW_BS000015
31
1
5
1
1
PW_BS000031
3
2
1
1
PW_BS000003
2
1
1
1
PW_BS000002
26
1
1
1
5
PW_BS000026
54
1
3
1
5
PW_BS000054
49
7
1
1
PW_BS000049
17
12
1
1
PW_BS000017
22
14
1
1
PW_BS000022
42
24
1
1
PW_BS000042
10
1
7
1
1
PW_BS000010
18
13
1
1
PW_BS000018
70
28
5
1
1
PW_BS000070
103
3
3
1
PW_BS000103
111
5
12
1
PW_BS000111
112
2
12
1
PW_BS000112
108
1
3
PW_BS000108
107
31
3
PW_BS000107
100
5
2
1
PW_BS000100
105
11
3
PW_BS000105
117
1
3
1
PW_BS000117
147
1
24
1
PW_BS000147
155
3
24
1
PW_BS000155
157
2
24
1
PW_BS000157
161
3
18
1
PW_BS000161
159
24
PW_BS000159
166
1
1
PW_BS000166
178
3
21
1
PW_BS000178
152
8
4
PW_BS000152
101
5
3
1
PW_BS000101
188
1
18
PW_BS000024
187
31
18
PW_BS000024
163
2
18
1
PW_BS000163
205
5
6
1
PW_BS000024
206
2
6
1
PW_BS000024
219
31
4
PW_BS000024
220
1
4
PW_BS000024
222
3
4
1
PW_BS000024
213
7
18
1
PW_BS000024
210
13
18
1
PW_BS000024
212
1
7
18
1
PW_BS000024
160
1
18
1
PW_BS000160
170
18
PW_BS000170
226
4
4
1
PW_BS000024
162
12
18
1
PW_BS000162
224
2
4
1
PW_BS000024
195
13
18
PW_BS000024
249
13
4
1
PW_BS000024
164
4
PW_BS000164
281
1
25
1
PW_BS000024
285
10
4
1
PW_BS000024
286
36
4
1
PW_BS000024
287
53
4
1
PW_BS000024
227
34
4
1
PW_BS000024
223
12
4
1
PW_BS000024
294
11
4
1
PW_BS000024
308
10
1
1
PW_BS000024
315
1
23
PW_BS000024
318
31
23
PW_BS000024
322
1
23
1
PW_BS000024
312
5
23
1
PW_BS000024
320
11
23
PW_BS000024
293
4
1
PW_BS000024
133
3
12
1
PW_BS000133
134
12
12
1
PW_BS000134
331
7
12
1
PW_BS000028
114
11
12
PW_BS000114
132
1
12
1
PW_BS000132
327
1
1
12
5
PW_BS000028
347
1
3
12
5
PW_BS000028
345
24
12
1
PW_BS000028
130
13
12
1
PW_BS000130
368
3
60
1
PW_BS000028
310
31
2
PW_BS000024
304
1
2
PW_BS000024
119
2
17
1
PW_BS000119
124
1
5
1
PW_BS000124
383
7
5
1
PW_BS000100
388
1
6
1
PW_BS000112
390
7
6
1
PW_BS000112
398
7
17
1
PW_BS000113
118
1
17
1
PW_BS000118
336
1
12
1
PW_BS000028
109
32
3
PW_BS000109
406
3
5
1
PW_BS000115
407
2
5
1
PW_BS000115
122
5
5
1
PW_BS000122
409
11
5
PW_BS000115
424
1
1
5
5
PW_BS000115
425
1
3
5
5
PW_BS000115
418
24
5
1
PW_BS000115
384
12
5
1
PW_BS000100
125
13
5
1
PW_BS000125
120
3
17
1
PW_BS000120
135
5
17
1
PW_BS000135
137
11
17
PW_BS000137
459
1
1
17
5
PW_BS000115
460
1
3
17
5
PW_BS000115
454
24
17
1
PW_BS000115
121
12
17
1
PW_BS000121
136
13
17
1
PW_BS000136
479
3
10
1
PW_BS000115
481
2
10
1
PW_BS000115
483
11
10
PW_BS000115
297
5
10
1
PW_BS000024
299
1
10
1
PW_BS000024
495
7
10
1
PW_BS000115
489
24
10
1
PW_BS000115
480
12
10
1
PW_BS000115
300
13
10
1
PW_BS000024
501
3
6
1
PW_BS000115
208
11
6
PW_BS000024
506
24
6
1
PW_BS000115
391
12
6
1
PW_BS000112
395
13
6
1
PW_BS000113
1
1
PW_BS000001
13
1
2
1
PW_BS000013
20
4
1
1
1
PW_BS000020
5
4
1
1
PW_BS000005
43
25
1
1
PW_BS000043
190
11
18
PW_BS000024
198
5
18
1
PW_BS000024
277
1
2
18
PW_BS000024
290
5
49
1
PW_BS000024
333
1
2
12
PW_BS000028
129
1
5
12
1
PW_BS000129
341
4
1
12
1
PW_BS000028
356
25
12
1
PW_BS000028
334
4
12
1
PW_BS000028
412
1
2
5
PW_BS000115
414
1
5
5
1
PW_BS000115
419
25
5
1
PW_BS000115
408
4
5
1
PW_BS000115
446
1
2
17
PW_BS000115
450
1
5
17
1
PW_BS000115
455
25
17
1
PW_BS000115
374
4
17
1
PW_BS000053
490
25
10
1
PW_BS000115
482
4
10
1
PW_BS000115
507
25
6
1
PW_BS000115
502
4
6
1
PW_BS000115
9
6
1
1
PW_BS000009
14
10
1
PW_BS000014
28
1
16
1
1
PW_BS000028
33
18
1
1
PW_BS000033
24
4
10
1
1
PW_BS000024
60
25
1
PW_BS000060
46
1
1
4
PW_BS000046
29
1
1
1
PW_BS000029
72
5
1
3
PW_BS000072
61
25
1
7
PW_BS000061
36
1
20
1
1
PW_BS000036
37
7
21
1
3
PW_BS000037
93
25
20
1
1
PW_BS000093
27
15
1
PW_BS000027
7
1
1
PW_BS000007
97
1
5
2
1
PW_BS000097
113
6
12
1
PW_BS000113
110
2
3
1
PW_BS000110
123
1
7
5
1
PW_BS000123
126
6
5
1
PW_BS000126
127
1
16
5
1
PW_BS000127
6
1
3
1
PW_BS000006
140
10
3
PW_BS000140
143
1
5
19
1
PW_BS000143
146
5
19
1
PW_BS000146
95
1
7
2
1
PW_BS000095
180
2
21
1
PW_BS000180
207
6
6
1
PW_BS000024
211
10
18
PW_BS000024
214
25
18
1
PW_BS000024
215
6
18
1
PW_BS000024
216
4
18
1
PW_BS000024
65
11
1
PW_BS000065
291
6
49
1
PW_BS000024
292
4
49
1
PW_BS000024
298
1
7
10
1
PW_BS000024
301
6
10
1
PW_BS000024
302
1
16
10
1
PW_BS000024
253
5
4
1
PW_BS000024
332
1
7
12
1
PW_BS000028
115
10
12
PW_BS000115
337
1
16
12
1
PW_BS000028
343
18
12
1
PW_BS000028
329
14
12
1
PW_BS000028
352
25
12
PW_BS000028
353
25
12
7
PW_BS000028
360
4
10
12
1
PW_BS000028
370
2
60
1
PW_BS000028
228
36
1
PW_BS000024
232
40
3
PW_BS000024
405
10
5
PW_BS000115
415
18
5
1
PW_BS000115
429
1
5
1
PW_BS000115
434
4
10
5
1
PW_BS000115
382
14
5
1
PW_BS000100
436
25
5
PW_BS000115
443
6
17
1
PW_BS000115
376
10
17
PW_BS000053
447
1
7
17
1
PW_BS000115
448
1
16
17
1
PW_BS000115
451
18
17
1
PW_BS000115
464
1
17
1
PW_BS000115
469
4
10
17
1
PW_BS000115
399
14
17
1
PW_BS000113
471
25
17
PW_BS000115
472
25
17
7
PW_BS000115
478
10
10
PW_BS000115
487
18
10
1
PW_BS000115
484
14
10
1
PW_BS000115
209
10
6
PW_BS000024
504
18
6
1
PW_BS000115
515
4
10
6
1
PW_BS000115
389
14
6
1
PW_BS000112
513
1
7
6
1
PW_BS000115
50
9
5
1
6
PW_BS000050
85
24
10
1
1
PW_BS000085
71
11
1
3
PW_BS000071
289
2
49
1
PW_BS000024
346
9
5
12
6
PW_BS000028
423
9
5
5
6
PW_BS000115
458
9
5
17
6
PW_BS000115
16
2
1
2
PW_BS000016
19
3
5
1
3
PW_BS000019
189
32
18
PW_BS000024
317
32
23
PW_BS000024
234
32
25
PW_BS000024
7748
Chorismate
HMDB0012199
Chorismic acid, more commonly known as its anionic form chorismate, is an important biochemical intermediate in plants and microorganisms. It is a precursor for the aromatic amino acids phenylalanine and tyrosine,indole, indole derivatives and tryptophan,2,3-dihydroxybenzoic acid (DHB) used for enterobactin biosynthesis,the plant hormone salicylic acid and many alkaloids and other aromatic metabolites. -- Wikipedia.
617-12-9
C00251
12039
17333
CPD-9517
11542
O[C@@H]1C=CC(=C[C@H]1OC(=C)C(O)=O)C(O)=O
C10H10O6
InChI=1S/C10H10O6/c1-5(9(12)13)16-8-4-6(10(14)15)2-3-7(8)11/h2-4,7-8,11H,1H2,(H,12,13)(H,14,15)/t7-,8-/m1/s1
WTFXTQVDAKGDEY-HTQZYQBOSA-N
(3R,4R)-3-[(1-carboxyeth-1-en-1-yl)oxy]-4-hydroxycyclohexa-1,5-diene-1-carboxylic acid
226.1828
226.047738052
-1.41
3
chorismic acid
0
-2
C00251
Chorismic acid;(3r,4r)-3-[(1-carboxyvinyl)oxy]-4-hydroxycyclohexa-1,5-diene-1-carboxylic acid;(3r-trans)-3-((1-carboxyethenyl)oxy)-4-hydroxy-1,5-cyclohexadiene-1-carboxylic acid;(3r,4r)-3-[(1-carboxyvinyl)oxy]-4-hydroxycyclohexa-1,5-diene-1-carboxylate;(3r-trans)-3-((1-carboxyethenyl)oxy)-4-hydroxy-1,5-cyclohexadiene-1-carboxylate
PW_C007748
Chorism
5164
94
8325
225
8329
151
42309
313
7823
Prephenate
HMDB0012283
Prephenate, also known as prephenic acid, belongs to the class of organic compounds known as gamma-keto acids and derivatives. These are organic compounds containing an aldehyde substituted with a keto group on the C4 carbon atom. Prephenate is soluble (in water) and a moderately acidic compound (based on its pKa). Prephenate exists in all living organisms, ranging from bacteria to humans. Prephenate participates in a number of enzymatic reactions. In particular, Prephenate can be biosynthesized from chorismate; which is catalyzed by the enzyme chorismate mutase:phea. Furthermore, Prephenate can be converted into phenylpyruvic acid through its interaction with the enzyme chorismate mutase:phea. Furthermore, Prephenate can be biosynthesized from chorismate through the action of the enzyme chorismate mutase:phea. Furthermore, Prephenate can be converted into phenylpyruvic acid; which is catalyzed by the enzyme chorismate mutase:phea. Furthermore, Prephenate can be biosynthesized from chorismate through the action of the enzyme chorismate mutase:tyra. Finally, Prephenate can be converted into 4-hydroxyphenylpyruvic acid through its interaction with the enzyme chorismate mutase:tyra. Outside of the human body, prephenate can be found in a number of food items such as garden tomato (var.), vaccinium (blueberry, cranberry, huckleberry), sacred lotus, and alpine sweetvetch. This makes prephenate a potential biomarker for the consumption of these food products. Prephenic acid, more commonly known by its anionic form prephenate, is an intermediate in the biosynthesis of the aromatic amino acids phenylalanine and tyrosine.
126-49-8
C00254
1028
16666
PREPHENATE
1001
OC1C=CC(CC(=O)C(O)=O)(C=C1)C(O)=O
C10H10O6
InChI=1S/C10H10O6/c11-6-1-3-10(4-2-6,9(15)16)5-7(12)8(13)14/h1-4,6,11H,5H2,(H,13,14)(H,15,16)
FPWMCUPFBRFMLH-UHFFFAOYSA-N
1-(2-carboxy-2-oxoethyl)-4-hydroxycyclohexa-2,5-diene-1-carboxylic acid
226.1828
226.047738052
-0.80
3
prephenic acid
0
-2
C00254
1-carboxy-4-hydroxy-2,5-cyclohexadiene-1-pyruvic acid;Pre;Prephenic acid;1-carboxy-4-hydroxy-alpha-oxo-2,5-cyclohexadiene-1-propanoic acid;1-carboxy-4-hydroxy-2,5-cyclohexadiene-1-pyruvate;1-carboxy-4-hydroxy-a-oxo-2,5-cyclohexadiene-1-propanoate;1-carboxy-4-hydroxy-a-oxo-2,5-cyclohexadiene-1-propanoic acid;1-carboxy-4-hydroxy-alpha-oxo-2,5-cyclohexadiene-1-propanoate;1-carboxy-4-hydroxy-α-oxo-2,5-cyclohexadiene-1-propanoate;1-carboxy-4-hydroxy-α-oxo-2,5-cyclohexadiene-1-propanoic acid
PW_C007823
Prephen
8326
225
8330
151
40034
Hydrogen Ion
HMDB0059597
Hydrogen ion is recommended by IUPAC as a general term for all ions of hydrogen and its isotopes. Depending on the charge of the ion, two different classes can be distinguished: positively charged ions and negatively charged ions. Under aqueous conditions found in biochemistry, hydrogen ions exist as the hydrated form hydronium, H3O+, but these are often still referred to as hydrogen ions or even protons by biochemists. [WikiPedia])
C00080
1038
15378
1010
[H+]
H
InChI=1S/p+1
GPRLSGONYQIRFK-UHFFFAOYSA-N
hydron
1.0079
1.007825032
0
hydron
1
0
H+;H(+);Hydrogen cation;Hydron;Proton
PW_C040034
H+
215
4
670
8
753
15
788
31
848
3
1116
2
1463
26
1464
54
2231
49
2780
17
4250
22
4254
42
4547
10
4576
18
4694
70
5241
103
5327
111
5353
112
5626
108
5639
107
5699
100
5720
105
5742
117
5963
147
6037
155
6070
157
6093
161
6130
159
6232
166
6483
178
6601
152
6692
101
6843
188
6910
187
7100
163
7168
205
7191
206
7453
219
7454
220
7472
222
7525
213
7532
210
7558
212
7572
160
7590
170
8195
225
8218
151
8243
226
8413
162
8420
224
9139
195
9155
249
11915
164
12015
281
12181
285
12246
286
12266
287
12521
227
13257
223
13325
294
15330
308
42329
315
42354
318
42401
322
42405
312
42454
320
76912
293
77136
133
77210
134
77372
331
77804
114
77955
132
77990
327
77991
347
78379
345
79929
130
80019
368
80387
310
80388
304
80722
119
93823
124
94823
383
110550
388
112855
94
113280
390
115537
398
115539
118
115856
336
116205
109
119973
406
120193
407
120549
122
120593
409
121170
424
121171
425
122569
418
122615
384
122687
125
122758
120
123183
135
123218
137
123742
459
123743
460
125141
454
125188
121
125273
136
125359
479
125550
481
125730
483
125736
297
125809
299
126517
495
126717
489
126766
480
126823
300
126902
501
127213
208
128308
506
128361
391
128430
395
1316
Carbon dioxide
HMDB0001967
Carbon dioxide is a colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. Carbon dioxide is produced during respiration by all animals, fungi and microorganisms that depend on living and decaying plants for food, either directly or indirectly. It is, therefore, a major component of the carbon cycle. Additionally, carbon dioxide is used by plants during photosynthesis to make sugars which may either be consumed again in respiration or used as the raw material to produce polysaccharides such as starch and cellulose, proteins and the wide variety of other organic compounds required for plant growth and development. When inhaled at concentrations much higher than usual atmospheric levels, it can produce a sour taste in the mouth and a stinging sensation in the nose and throat. These effects result from the gas dissolving in the mucous membranes and saliva, forming a weak solution of carbonic acid. Carbon dioxide is used by the food industry, the oil industry, and the chemical industry. Carbon dioxide is used to produce carbonated soft drinks and soda water. Traditionally, the carbonation in beer and sparkling wine comes about through natural fermentation, but some manufacturers carbonate these drinks artificially.
124-38-9
C00011
280
16526
274
O=C=O
CO2
InChI=1S/CO2/c2-1-3
CURLTUGMZLYLDI-UHFFFAOYSA-N
methanedione
44.0095
43.989829244
0.63
0
carbon dioxide
0
0
DBMET00423
FDB014084
Carbon oxide;Carbon-12 dioxide;Carbonic acid anhydride;Carbonic acid gas;Carbonic anhydride;[co2];Co2;E 290;E-290;E290;R-744
PW_C001316
CO2
50
8
121
1
204
4
480
13
503
18
640
3
677
31
695
20
806
5
1133
43
1638
49
1745
2
2551
17
3144
70
5283
103
5320
111
5750
108
5771
101
5968
100
6026
155
6078
161
6471
178
6637
107
6922
190
7017
160
7035
163
7061
188
7163
205
7308
198
7333
213
7461
222
7530
210
8215
225
8223
151
9158
249
11849
277
11908
170
12464
226
12688
290
42626
315
43523
318
76994
293
77122
133
77170
132
77470
333
77739
112
77750
129
77763
341
78077
134
78405
356
78427
334
78941
331
79227
130
80008
368
80675
119
80717
135
94836
384
113291
391
115549
121
119954
406
120089
122
120155
407
120364
412
120556
414
120833
419
120922
124
120991
408
121284
125
121505
383
122744
120
123011
446
123190
450
123418
455
123489
118
123556
374
123855
136
124063
398
125344
479
125460
297
125516
481
125824
490
125870
299
125931
482
126280
480
126887
501
127052
206
127277
507
127331
388
127390
502
1420
Water
HMDB0002111
Water is a chemical substance that is essential to all known forms of life. It appears colorless to the naked eye in small quantities, though it is actually slightly blue in color. It covers 71% of Earth's surface. Current estimates suggest that there are 1.4 billion cubic kilometers (330 million m3) of it available on Earth, and it exists in many forms. It appears mostly in the oceans (saltwater) and polar ice caps, but it is also present as clouds, rain water, rivers, freshwater aquifers, lakes, and sea ice. Water in these bodies perpetually moves through a cycle of evaporation, precipitation, and runoff to the sea. Clean water is essential to human life. In many parts of the world, it is in short supply. From a biological standpoint, water has many distinct properties that are critical for the proliferation of life that set it apart from other substances. It carries out this role by allowing organic compounds to react in ways that ultimately allow replication. All known forms of life depend on water. Water is vital both as a solvent in which many of the body's solutes dissolve and as an essential part of many metabolic processes within the body. Metabolism is the sum total of anabolism and catabolism. In anabolism, water is removed from molecules (through energy requiring enzymatic chemical reactions) in order to grow larger molecules (e.g. starches, triglycerides and proteins for storage of fuels and information). In catabolism, water is used to break bonds in order to generate smaller molecules (e.g. glucose, fatty acids and amino acids to be used for fuels for energy use or other purposes). Water is thus essential and central to these metabolic processes. Water is also central to photosynthesis and respiration. Photosynthetic cells use the sun's energy to split off water's hydrogen from oxygen. Hydrogen is combined with CO2 (absorbed from air or water) to form glucose and release oxygen. All living cells use such fuels and oxidize the hydrogen and carbon to capture the sun's energy and reform water and CO2 in the process (cellular respiration). Water is also central to acid-base neutrality and enzyme function. An acid, a hydrogen ion (H+, that is, a proton) donor, can be neutralized by a base, a proton acceptor such as hydroxide ion (OH-) to form water. Water is considered to be neutral, with a pH (the negative log of the hydrogen ion concentration) of 7. Acids have pH values less than 7 while bases have values greater than 7. Stomach acid (HCl) is useful to digestion. However, its corrosive effect on the esophagus during reflux can temporarily be neutralized by ingestion of a base such as aluminum hydroxide to produce the neutral molecules water and the salt aluminum chloride. Human biochemistry that involves enzymes usually performs optimally around a biologically neutral pH of 7.4. (Wikipedia).
7732-18-5
C00001
962
15377
937
O
H2O
InChI=1S/H2O/h1H2
XLYOFNOQVPJJNP-UHFFFAOYSA-N
water
18.0153
18.010564686
1
water
0
0
FDB013390
Dihydrogen oxide;Steam;[oh2];Acqua;Agua;Aqua;Bound water;Dihydridooxygen;Eau;H2o;Hoh;Hydrogen hydroxide;Wasser
PW_C001420
H2O
55
8
94
9
109
5
139
4
151
3
162
14
481
13
526
15
624
28
652
10
691
20
770
33
823
18
838
2
1094
31
1377
49
1465
54
1590
43
2018
24
2532
22
2678
60
2727
46
2778
17
2805
29
3143
70
3164
72
3634
61
4598
36
4727
37
4941
93
5030
27
5156
7
5195
97
5214
100
5227
94
5236
103
5297
105
5319
111
5343
113
5355
112
5402
110
5470
123
5483
125
5492
126
5507
127
5534
130
5537
114
5541
129
5591
135
5608
118
5622
108
5691
6
5759
140
5778
101
5841
143
5853
146
5877
107
5890
95
5910
147
5940
151
6032
155
6059
157
6087
161
6123
163
6133
159
6215
1
6218
166
6477
178
6507
180
6600
152
6713
117
6840
188
6888
160
7162
205
7181
207
7193
206
7211
211
7228
213
7238
214
7243
215
7295
198
7350
216
7388
210
7401
212
7467
222
7492
224
7500
190
7588
170
8201
225
8237
226
8414
162
9265
26
11850
277
11922
164
12011
281
12213
285
12250
286
12264
287
12327
249
12520
227
12632
65
12693
290
12705
291
12715
292
13007
298
13019
300
13025
301
13037
302
13261
223
13327
294
15340
308
42327
315
42695
318
43691
322
76914
293
77019
253
77102
132
77131
133
77215
134
77378
331
77397
332
77471
333
77516
115
77536
334
77628
336
77722
337
77759
341
77816
343
77982
347
78071
329
78235
352
78242
353
78270
356
79113
360
80014
368
80039
370
80591
228
80656
119
93830
383
94794
384
110557
390
110639
391
115844
398
119879
232
119915
122
119963
406
120008
407
120046
408
120113
124
120365
412
120430
405
120438
409
120606
415
120794
414
121158
425
121240
429
121351
121
121381
419
121607
434
122118
382
122384
436
122753
120
122797
374
122804
443
123012
446
123064
376
123072
137
123131
447
123142
136
123162
448
123231
451
123384
450
123730
460
123810
464
123940
455
124165
469
124670
399
124938
471
124945
472
125305
297
125353
479
125386
481
125424
482
125480
299
125682
483
125707
478
125745
487
126054
490
126238
495
126273
484
126764
480
126896
501
126963
502
127017
388
127177
208
127199
209
127227
504
127506
507
127576
515
127836
389
128082
395
128176
513
131
Phenylpyruvic acid
HMDB0000205
Phenylpyruvic acid is a keto-acid that is an intermediate or catabolic byproduct of phenylalanine metabolism. It has a slight honey-like odor. Levels of phenylpyruvate are normally very low in blood or urine. High levels of phenylpyruvic acid can be found in the urine of individuals with phenylketonuria (PKU). PKU is due to lack of the enzyme phenylalanine hydroxylase (PAH), so that phenylalanine is converted not to tyrosine but to phenylpyruvic acid. In particular, excessive phenylalanine can be metabolized into phenylketones through, a transaminase pathway route involving glutamate. Metabolites of this transamination reaction include phenylacetate, phenylpyruvate and phenethylamine. In persons with PKU, dietary phenylalanine either accumulates in the body or some of it is converted to phenylpyruvic acid. Individuals with PKU tend to excrete large quantities of phenylpyruvate, phenylacetate and phenyllactate, along with phenylalanine, in their urine. If untreated, mental retardation effects and microcephaly are evident by the first year along with other symptoms which include: unusual irritability, epileptic seizures and skin lesions. Hyperactivity, EEG abnormalities and seizures, and severe learning disabilities are major clinical problems later in life. A "musty or mousy" odor of skin, hair, sweat and urine (due to phenylacetate accumulation); and a tendency to hypopigmentation and eczema are also observed. The neural-development effects of PKU are primarily due to the disruption of neurotransmitter synthesis. In particular, phenylalanine is a large, neutral amino acid which moves across the blood-brain barrier (BBB) via the large neutral amino acid transporter (LNAAT). Excessive phenylalanine in the blood saturates the transporter. Thus, excessive levels of phenylalanine significantly decrease the levels of other LNAAs in the brain. But since these amino acids are required for protein and neurotransmitter synthesis, phenylalanine accumulation disrupts brain development, leading to mental retardation.
156-06-9
C00166
997
30851
PHENYL-PYRUVATE
972
DB03884
OC(=O)C(=O)CC1=CC=CC=C1
C9H8O3
InChI=1S/C9H8O3/c10-8(9(11)12)6-7-4-2-1-3-5-7/h1-5H,6H2,(H,11,12)
BTNMPGBKDVTSJY-UHFFFAOYSA-N
2-oxo-3-phenylpropanoic acid
164.158
164.047344122
-2.25
1
phenylpyruvic acid
0
-1
FDB020197
2-oxo-3-phenylpropanoate;2-oxo-3-phenylpropanoic acid;3-phenyl-2-oxopropanoate;3-phenyl-2-oxopropanoic acid;3-phenylpyruvate;3-phenylpyruvic acid;Keto-phenylpyruvate;Phenylpyroracemate;Phenylpyroracemic acid;Phenylpyruvate;Alpha-ketohydrocinnamate;Alpha-ketohydrocinnamic acid;B-phenylpyruvate;B-phenylpyruvic acid;Beta-phenylpyruvate;Beta-phenylpyruvic acid;Alpha-oxo-benzenepropanoic acid;Phenylbrenztraubensaeure;Phenylpyruvic acid;A-ketohydrocinnamate;A-ketohydrocinnamic acid;α-ketohydrocinnamate;α-ketohydrocinnamic acid;A-oxo-benzenepropanoate;A-oxo-benzenepropanoic acid;Alpha-oxo-benzenepropanoate;α-oxo-benzenepropanoate;α-oxo-benzenepropanoic acid;β-phenylpyruvate;β-phenylpyruvic acid;Keto-phenylpyruvic acid;2-hydroxy-3-phenyl-2-propenoic acid, 9ci;2-oxo-3-phenylpropanoic acid (mixture oxo and keto);A-hydroxycinnamic acid;A-oxobenzenepropanoic acid, 9ci;Fema 3892
PW_C000131
Ppyr
1280
8
78464
111
120998
122
123563
135
95
L-Glutamic acid
HMDB0000148
Glutamic acid (Glu), also referred to as glutamate (the anion), is one of the 20 proteinogenic amino acids. It is not among the essential amino acids. Glutamate is a key molecule in cellular metabolism. In humans, dietary proteins are broken down by digestion into amino acids, which serves as metabolic fuel or other functional roles in the body. Glutamate is the most abundant fast excitatory neurotransmitter in the mammalian nervous system. At chemical synapses, glutamate is stored in vesicles. Nerve impulses trigger release of glutamate from the pre-synaptic cell. In the opposing post-synaptic cell, glutamate receptors, such as the NMDA receptor, bind glutamate and are activated. Because of its role in synaptic plasticity, it is believed that glutamic acid is involved in cognitive functions like learning and memory in the brain. Glutamate transporters are found in neuronal and glial membranes. They rapidly remove glutamate from the extracellular space. In brain injury or disease, they can work in reverse and excess glutamate can accumulate outside cells. This process causes calcium ions to enter cells via NMDA receptor channels, leading to neuronal damage and eventual cell death, and is called excitotoxicity. The mechanisms of cell death include: * Damage to mitochondria from excessively high intracellular Ca2+. * Glu/Ca2+-mediated promotion of transcription factors for pro-apoptotic genes, or downregulation of transcription factors for anti-apoptotic genes. Excitotoxicity due to glutamate occurs as part of the ischemic cascade and is associated with stroke and diseases like amyotrophic lateral sclerosis, lathyrism, and Alzheimer's disease. glutamic acid has been implicated in epileptic seizures. Microinjection of glutamic acid into neurons produces spontaneous depolarization around one second apart, and this firing pattern is similar to what is known as paroxysmal depolarizing shift in epileptic attacks. This change in the resting membrane potential at seizure foci could cause spontaneous opening of voltage activated calcium channels, leading to glutamic acid release and further depolarization. (http://en.wikipedia.org/wiki/Glutamic_acid).
56-86-0
C00025
33032
16015
GLT
30572
DB00142
N[C@@H](CCC(O)=O)C(O)=O
C5H9NO4
InChI=1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)/t3-/m0/s1
WHUUTDBJXJRKMK-VKHMYHEASA-N
(2S)-2-aminopentanedioic acid
147.1293
147.053157781
-0.26
3
L-glutamic acid
0
-1
FDB012535
(2s)-2-aminopentanedioate;(2s)-2-aminopentanedioic acid;(s)-(+)-glutamate;(s)-(+)-glutamic acid;(s)-2-aminopentanedioate;(s)-2-aminopentanedioic acid;(s)-glutamate;(s)-glutamic acid;1-amino-propane-1,3-dicarboxylate;1-amino-propane-1,3-dicarboxylic acid;1-aminopropane-1,3-dicarboxylate;1-aminopropane-1,3-dicarboxylic acid;2-aminoglutarate;2-aminoglutaric acid;2-aminopentanedioate;2-aminopentanedioic acid;Aciglut;Aminoglutarate;Aminoglutaric acid;E;Glt;Glu;Glusate;Glut;Glutacid;Glutamicol;Glutamidex;Glutaminate;Glutaminic acid;Glutaminol;Glutaton;L-(+)-glutamate;L-(+)-glutamic acid;L-glu;L-glutamate;L-glutaminate;L-glutaminic acid;L-a-aminoglutarate;L-a-aminoglutaric acid;L-alpha-aminoglutarate;L-alpha-aminoglutaric acid;A-aminoglutarate;A-aminoglutaric acid;A-glutamate;A-glutamic acid;Alpha-aminoglutarate;Alpha-aminoglutaric acid;Alpha-glutamate;Alpha-glutamic acid;Acide glutamique;Acido glutamico;Acidum glutamicum;Glutamate;Glutamic acid;L-glutaminsaeure
PW_C000095
Glu
16
2
44
3
65
8
119
1
138
4
164
14
969
9
1105
42
1448
50
1456
26
1462
54
5323
111
5344
113
5415
117
5439
118
5565
132
5631
107
5632
108
5859
105
6006
147
6071
157
6191
94
6531
85
6838
187
6844
188
7092
72
7093
71
7165
205
7182
207
7514
224
7518
151
8208
225
8373
220
11792
198
11855
161
12004
222
12621
31
12683
289
12697
290
42348
315
42349
318
42845
320
77020
253
77332
133
77525
112
77971
346
77977
327
77981
347
78291
345
80649
135
120023
124
120040
122
120086
407
120347
406
120692
126
120816
418
121147
423
121153
424
121157
425
122833
119
122997
120
123299
443
123401
454
123719
458
123725
459
123729
460
125401
299
125418
297
125457
481
125667
479
125769
301
125802
489
126941
388
126995
206
127162
501
127257
506
134
Oxoglutaric acid
HMDB0000208
Oxoglutaric acid, also known as alpha-ketoglutarate, alpha-ketoglutaric acid, AKG, or 2-oxoglutaric acid, is classified as a gamma-keto acid or a gamma-keto acid derivative. gamma-Keto acids are organic compounds containing an aldehyde substituted with a keto group on the C4 carbon atom. alpha-Ketoglutarate is considered to be soluble (in water) and acidic. alpha-Ketoglutarate is a key molecule in the TCA cycle, playing a fundamental role in determining the overall rate of this important metabolic process (PMID: 26759695). In the TCA cycle, AKG is decarboxylated to succinyl-CoA and carbon dioxide by AKG dehydrogenase, which functions as a key control point of the TCA cycle. Additionally, AKG can be generated from isocitrate by oxidative decarboxylation catalyzed by the enzyme known as isocitrate dehydrogenase (IDH). In addition to these routes of production, AKG can be produced from glutamate by oxidative deamination via glutamate dehydrogenase, and as a product of pyridoxal phosphate-dependent transamination reactions (mediated by branched-chain amino acid transaminases) in which glutamate is a common amino donor. AKG is a nitrogen scavenger and a source of glutamate and glutamine that stimulates protein synthesis and inhibits protein degradation in muscles. In particular, AKG can decrease protein catabolism and increase protein synthesis to enhance bone tissue formation in skeletal muscles (PMID: 26759695). Interestingly, enteric feeding of AKG supplements can significantly increase circulating plasma levels of hormones such as insulin, growth hormone, and insulin-like growth factor-1 (PMID: 26759695). It has recently been shown that AKG can extend the lifespan of adult C. elegans by inhibiting ATP synthase and TOR (PMID: 24828042). In combination with molecular oxygen, alpha-ketoglutarate is required for the hydroxylation of proline to hydroxyproline in the production of type I collagen. A recent study has shown that alpha-ketoglutarate promotes TH1 differentiation along with the depletion of glutamine thereby favouring Treg (regulatory T-cell) differentiation (PMID: 26420908). alpha-Ketoglutarate has been found to be associated with fumarase deficiency, 2-ketoglutarate dehydrogenase complex deficiency, and D-2-hydroxyglutaric aciduria, which are all inborn errors of metabolism (PMID: 8338207).
328-50-7
C00026
51
30915
2-KETOGLUTARATE
50
DB02926
OC(=O)CCC(=O)C(O)=O
C5H6O5
InChI=1S/C5H6O5/c6-3(5(9)10)1-2-4(7)8/h1-2H2,(H,7,8)(H,9,10)
KPGXRSRHYNQIFN-UHFFFAOYSA-N
2-oxopentanedioic acid
146.0981
146.021523302
-0.44
2
oxoglutarate
0
-2
FDB003361
2-ketoglutarate;2-ketoglutaric acid;2-oxo-1,5-pentanedioate;2-oxo-1,5-pentanedioic acid;2-oxoglutarate;2-oxoglutaric acid;2-oxopentanedioate;2-oxopentanedioic acid;Oxoglutarate;Alpha-ketoglutaric acid;Oxoglutaric acid;A-ketoglutarate;A-ketoglutaric acid;Alpha-ketoglutarate;α-ketoglutarate;α-ketoglutaric acid
PW_C000134
AKG
15
2
42
3
141
4
146
8
499
18
673
31
1108
42
1263
5
1447
50
1455
26
1467
54
5375
103
5414
117
5438
118
5564
132
6008
147
6036
155
6069
157
6092
161
6482
178
6530
85
7471
222
7515
224
7519
151
8209
225
8374
220
11863
198
12681
289
77054
253
77135
133
77481
111
77523
112
77746
129
77967
345
77970
346
77976
327
77984
347
78425
334
80018
368
80694
135
113162
94
119972
406
120022
124
120084
407
120174
122
120552
414
120814
418
120989
408
121146
423
121152
424
121160
425
122757
120
122831
119
123186
450
123399
454
123554
374
123718
458
123724
459
123732
460
125357
479
125400
299
125455
481
125533
297
125800
489
125929
482
126900
501
126940
388
126993
206
127066
205
127255
506
127388
502
104
L-Phenylalanine
HMDB0000159
Phenylalanine is an essential amino acid and the precursor of the amino acid tyrosine. Like tyrosine, phenylalanine is also a precursor for catecholamines including tyramine, dopamine, epinephrine, and norepinephrine. Catecholamines are neurotransmitters that act as adrenalin-like substances. Interestingly, several psychotropic drugs (mescaline, morphine, codeine, and papaverine) also have phenylalanine as a constituent. Phenylalanine is highly concentrated in the human brain and plasma. Normal metabolism of phenylalanine requires biopterin, iron, niacin, vitamin B6, copper, and vitamin C. An average adult ingests 5 g of phenylalanine per day and may optimally need up to 8 g daily. Phenylalanine is highly concentrated in a number of high protein foods, such as meat, cottage cheese, and wheat germ. An additional dietary source of phenylalanine is artificial sweeteners containing aspartame. As a general rule, aspartame should be avoided by phenylketonurics and pregnant women. When present in sufficiently high levels, phenylalanine can act as a neurotoxin and a metabotoxin. A neurotoxin is a compound that disrupts or attacks neural cells and neural tissue. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of phenylalanine are associated with at least five inborn errors of metabolism, including Hartnup disorder, hyperphenylalaninemia due to guanosine triphosphate cyclohydrolase deficiency, phenylketonuria (PKU), tyrosinemia type 2 (or Richner-Hanhart syndrome), and tyrosinemia type III (TYRO3). Phenylketonurics have elevated serum plasma levels of phenylalanine up to 400 times normal. High plasma concentrations of phenylalanine influence the blood-brain barrier transport of large neutral amino acids. The high plasma phenylalanine concentrations increase phenylalanine entry into the brain and restrict the entry of other large neutral amino acids (PMID: 19191004). Phenylalanine has been found to interfere with different cerebral enzyme systems. Untreated phenylketonuria (PKU) can lead to intellectual disability, seizures, behavioural problems, and mental disorders. It may also result in a musty smell and lighter skin. Classic PKU dramatically affects myelination and white matter tracts in untreated infants; this may be one major cause of neurological disorders associated with phenylketonuria. Mild phenylketonuria can act as an unsuspected cause of hyperactivity, learning problems, and other developmental problems in children. It has been recently suggested that PKU may resemble amyloid diseases, such as Alzheimer's disease and Parkinson's disease, due to the formation of toxic amyloid-like assemblies of phenylalanine (PMID: 22706200). Phenylalanine also has some potential benefits. Phenylalanine can act as an effective pain reliever. Its use in premenstrual syndrome and Parkinson's may enhance the effects of acupuncture and electric transcutaneous nerve stimulation (TENS). Phenylalanine and tyrosine, like L-DOPA, produce a catecholamine-like effect. Phenylalanine is better absorbed than tyrosine and may cause fewer headaches. Low phenylalanine diets have been prescribed for certain cancers with mixed results. For instance, some tumours use more phenylalanine than others (particularly melatonin-producing tumours called melanomas).
63-91-2
C00079
6140
17295
PHE
5910
DB00120
N[C@@H](CC1=CC=CC=C1)C(O)=O
C9H11NO2
InChI=1S/C9H11NO2/c10-8(9(11)12)6-7-4-2-1-3-5-7/h1-5,8H,6,10H2,(H,11,12)/t8-/m0/s1
COLNVLDHVKWLRT-QMMMGPOBSA-N
(2S)-2-amino-3-phenylpropanoic acid
165.1891
165.078978601
-1.60
2
L-phenylalanine
0
0
FDB014705
(-)-beta-phenylalanine;(l)-phenylalanine;(s)-(-)-phenylalanine;(s)-2-amino-3-phenylpropionate;(s)-2-amino-3-phenylpropionic acid;(s)-2-amino-3-phenylpropanoate;(s)-2-amino-3-phenylpropanoic acid;(s)-phenylalanine;(s)-alpha-amino-benzenepropanoate;(s)-alpha-amino-benzenepropanoic acid;(s)-alpha-amino-beta-phenylpropionate;(s)-alpha-amino-beta-phenylpropionic acid;(s)-alpha-aminobenzenepropanoate;(s)-alpha-aminobenzenepropanoic acid;(s)-alpha-aminohydrocinnamate;(s)-alpha-aminohydrocinnamic acid;3-phenyl-l-alanine;L-2-amino-3-phenylpropionate;L-2-amino-3-phenylpropionic acid;Phe;Phenyl-alanine;Phenylalamine;Phenylalanine;Alpha-aminohydrocinnamate;Alpha-aminohydrocinnamic acid;Beta-phenyl-l-alanine;Beta-phenyl-alpha-alanine;Beta-phenylalanine;F;(s)-a-amino-b-phenylpropionate;(s)-a-amino-b-phenylpropionic acid;(s)-α-amino-β-phenylpropionate;(s)-α-amino-β-phenylpropionic acid;B-phenyl-l-alanine;β-phenyl-l-alanine
PW_C000104
Phe
1279
8
5669
107
5670
108
5888
105
8340
225
8341
151
42458
315
42459
318
77061
253
78463
111
120997
122
123562
135
1065
Oxygen
HMDB0001377
Oxygen is the third most abundant element in the universe after hydrogen and helium and the most abundant element by mass in the Earth's crust. Diatomic oxygen gas constitutes 20.9% of the volume of air. All major classes of structural molecules in living organisms, such as proteins, carbohydrates, and fats, contain oxygen, as do the major inorganic compounds that comprise animal shells, teeth, and bone. Oxygen in the form of O2 is produced from water by cyanobacteria, algae and plants during photosynthesis and is used in cellular respiration for all living organisms. Green algae and cyanobacteria in marine environments provide about 70% of the free oxygen produced on earth and the rest is produced by terrestrial plants. Oxygen is used in mitochondria to help generate adenosine triphosphate (ATP) during oxidative phosphorylation. For animals, a constant supply of oxygen is indispensable for cardiac viability and function. To meet this demand, an adult human, at rest, inhales 1.8 to 2.4 grams of oxygen per minute. This amounts to more than 6 billion tonnes of oxygen inhaled by humanity per year. At a resting pulse rate, the heart consumes approximately 8-15 ml O2/min/100 g tissue. This is significantly more than that consumed by the brain (approximately 3 ml O2/min/100 g tissue) and can increase to more than 70 ml O2/min/100 g myocardial tissue during vigorous exercise. As a general rule, mammalian heart muscle cannot produce enough energy under anaerobic conditions to maintain essential cellular processes; thus, a constant supply of oxygen is indispensable to sustain cardiac function and viability. However, the role of oxygen and oxygen-associated processes in living systems is complex, and they and can be either beneficial or contribute to cardiac dysfunction and death (through reactive oxygen species). Reactive oxygen species (ROS) are a family of oxygen-derived free radicals that are produced in mammalian cells under normal and pathologic conditions. Many ROS, such as the superoxide anion (O2-)and hydrogen peroxide (H2O2), act within blood vessels, altering mechanisms mediating mechanical signal transduction and autoregulation of cerebral blood flow. Reactive oxygen species are believed to be involved in cellular signaling in blood vessels in both normal and pathologic states. The major pathway for the production of ROS is by way of the one-electron reduction of molecular oxygen to form an oxygen radical, the superoxide anion (O2-). Within the vasculature there are several enzymatic sources of O2-, including xanthine oxidase, the mitochondrial electron transport chain, and nitric oxide (NO) synthases. Studies in recent years, however, suggest that the major contributor to O2- levels in vascular cells is the membrane-bound enzyme NADPH-oxidase. Produced O2- can react with other radicals, such as NO, or spontaneously dismutate to produce hydrogen peroxide (H2O2). In cells, the latter reaction is an important pathway for normal O2- breakdown and is usually catalyzed by the enzyme superoxide dismutase (SOD). Once formed, H2O2 can undergo various reactions, both enzymatic and nonenzymatic. The antioxidant enzymes catalase and glutathione peroxidase act to limit ROS accumulation within cells by breaking down H2O2 to H2O. Metabolism of H2O2 can also produce other, more damaging ROS. For example, the endogenous enzyme myeloperoxidase uses H2O2 as a substrate to form the highly reactive compound hypochlorous acid. Alternatively, H2O2 can undergo Fenton or Haber-Weiss chemistry, reacting with Fe2+/Fe3+ ions to form toxic hydroxyl radicals (-.OH). (PMID: 17027622, 15765131).
7782-44-7
C00007
977
15379
CPD-6641
952
O=O
O2
InChI=1S/O2/c1-2
MYMOFIZGZYHOMD-UHFFFAOYSA-N
oxidanone
31.9988
31.989829244
0
singlet oxygen
0
0
FDB022589
Dioxygen;Molecular oxygen;O2;Oxygen;Oxygen molecule;[oo];Dioxygene;Disauerstoff;E 948;E-948;E948
PW_C001065
O2
95
9
110
5
245
16
500
18
505
8
549
14
625
28
638
3
649
10
674
31
688
20
754
15
763
4
769
33
836
2
1375
49
2016
24
2531
22
2803
29
4260
42
4747
13
5467
123
5480
125
5493
126
5508
127
5809
108
5973
147
6129
159
7006
188
7032
163
7050
160
7319
213
7533
210
7560
212
8395
151
11816
216
11864
198
11883
215
11894
211
12057
225
12063
164
12247
286
12279
226
12325
249
12706
291
12716
292
13004
298
13016
300
13026
301
13038
302
13260
223
42276
17
42657
315
76910
293
77044
294
77214
134
77350
111
77363
130
77377
331
77395
332
77497
113
77512
115
77537
334
77626
336
77723
337
77736
112
77747
129
77756
341
77805
114
77812
133
78070
329
78151
132
78381
345
78805
343
79111
360
120047
408
120383
122
120426
405
120542
407
120553
414
120594
409
120601
406
120883
415
121045
124
121104
383
121605
434
121656
429
122117
382
122573
418
122689
384
122798
374
122822
443
123027
135
123060
376
123128
447
123139
136
123163
448
123176
119
123187
450
123219
137
123226
120
123459
451
123609
118
123669
398
124163
469
124214
464
124669
399
125145
454
125275
121
125425
482
125706
478
125731
483
125737
297
125740
479
125884
481
126100
299
126272
484
126522
495
126721
489
126825
480
126964
502
126986
207
127198
209
127214
208
127219
205
127222
501
127305
504
127345
206
127557
388
127574
515
127835
389
128081
395
128095
390
128312
506
128432
391
1148
Pyridoxal 5'-phosphate
HMDB0001491
This is the active form of vitamin B6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (pyridoxamine). -- Pubchem; Pyridoxal-phosphate (PLP, pyridoxal-5'-phosphate) is a cofactor of many enzymatic reactions. It is the active form of vitamin B6 which comprises three natural organic compounds, pyridoxal, pyridoxamine and pyridoxine. -- Wikipedia.
54-47-7
C00018
1051
18405
PYRIDOXAL_PHOSPHATE
1022
DB00114
CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O
C8H10NO6P
InChI=1S/C8H10NO6P/c1-5-8(11)7(3-10)6(2-9-5)4-15-16(12,13)14/h2-3,11H,4H2,1H3,(H2,12,13,14)
NGVDGCNFYWLIFO-UHFFFAOYSA-N
[(4-formyl-5-hydroxy-6-methylpyridin-3-yl)methoxy]phosphonic acid
247.1419
247.024573569
-1.64
3
pyridoxal phosphate
0
-2
FDB021820
Apolon b6;Biosechs;Codecarboxylase;Coenzyme b6;Hairoxal;Hexermin-p;Hi-pyridoxin;Hiadelon;Himitan;Pal-p;Plp;Phosphopyridoxal;Phosphopyridoxal coenzyme;Pidopidon;Piodel;Pydoxal;Pyridoxal 5'-phosphate;Pyridoxal 5-phosphate;Pyridoxal p;Pyridoxal phosphate;Pyridoxal-p;Pyridoxyl phosphate;Pyromijin;Sechvitan;Vitahexin-p;Vitazechs;3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinecarboxaldehyde;3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde 5-phosphate;Phosphoric acid mono-(4-formyl-5-hydroxy-6-methyl-pyridin-3-ylmethyl) ester;Pyridoxal 5-monophosphoric acid ester;Pyridoxal 5'-(dihydrogen phosphate);Pyridoxal-5'-phosphate;Pyridoxal 5'-phosphoric acid;3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde 5-phosphoric acid;Phosphate mono-(4-formyl-5-hydroxy-6-methyl-pyridin-3-ylmethyl) ester;Pyridoxal 5-monophosphate ester;Pyridoxal 5'-(dihydrogen phosphoric acid);Pyridoxal 5-phosphoric acid;Pyridoxal phosphoric acid;Pyridoxal-5'-phosphoric acid
PW_C001148
Pyr-5'P
18
2
32
4
45
3
51
8
122
1
401
19
696
20
1110
42
1450
50
1458
26
2120
10
2150
49
5325
111
5416
117
5421
103
5441
118
5455
120
5567
132
5581
133
6533
85
7018
160
7167
205
7216
212
7222
213
11858
161
12175
151
12623
31
12628
18
12684
289
12689
290
77017
253
77037
225
77041
293
77052
224
77526
112
77764
341
77973
346
77979
327
78292
345
78855
332
78862
331
80696
135
98630
7
119912
122
120024
124
120029
406
120087
407
120817
418
121149
423
121155
424
122069
123
122076
383
122834
119
123402
454
123721
458
123727
459
124620
447
124627
398
125302
297
125402
299
125407
479
125458
481
125803
489
126224
298
126231
495
126942
388
126947
501
126996
206
127258
506
127786
513
127793
390
42923
D-phenylalanine
DL-PHENYLALANINE, also known as F or PHE, belongs to the class of organic compounds known as phenylalanine and derivatives. Phenylalanine and derivatives are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom. DL-PHENYLALANINE exists as a solid, slightly soluble (in water), and a moderately acidic compound (based on its pKa). DL-PHENYLALANINE is also a parent compound for other transformation products, including but not limited to, 4-nitrophenylalanine, methyl 4-amino-N-(tert-butoxycarbonyl)phenylalaninate, and gamma-glutamylphenylalanine..
6919011
N[C@@H](CC1=CC=CC=C1)C(O)=O
C9H11NO2
InChI=1S/C9H11NO2/c10-8(9(11)12)6-7-4-2-1-3-5-7/h1-5,8H,6,10H2,(H,11,12)/t8-/m0/s1
COLNVLDHVKWLRT-QMMMGPOBSA-N
(2S)-2-amino-3-phenylpropanoic acid
165.1891
165.078978601
-1.60
2
L-phenylalanine
0
0
D-α-amino-β-phenylpropionic acid
PW_C042923
D-Phlan
6344
107
6457
108
42429
315
42430
318
6723
2-Phenylacetamide
HMDB0010715
2-Phenylacetamide is an intermediate in phenylalanine metabolism and styrene degradation(KEGG ID C02505). It is the third to last step in the synthesis of phenylacetylglutamine and is converted from phenylalanine via the enzyme phenylalanine 2-monooxygenase [EC:1.13.12.9]. It is then converted to phenylacetate via the enzyme amidase [EC:3.5.1.4].
103-81-1
C02505
7680
16562
7397
NC(=O)CC1=CC=CC=C1
C8H9NO
InChI=1S/C8H9NO/c9-8(10)6-7-4-2-1-3-5-7/h1-5H,6H2,(H2,9,10)
LSBDFXRDZJMBSC-UHFFFAOYSA-N
2-phenylacetamide
135.1632
135.068413915
-1.55
1
phenylacetamide
0
0
C02505
(alpha-)2-phenylacetamide;2-phenyl-acetamide;Benzeneacetamide;Phenyl-beta-acetylamine;Phenylacetamide;Phenylacetic acid amide;Alpha-phenylacetamide;Alpha-toluamide;Alpha-toluimidic acid;Beta-phenyl-acetylamine;A-phenylacetamide;α-phenylacetamide;A-toluamide;α-toluamide;Phenyl-b-acetylamine;Phenyl-β-acetylamine;Phenylacetate amide
PW_C006723
2Phen
42924
ferroheme b
Ferroheme b belongs to the class of organic compounds known as metalloporphyrins. These are polycyclic compounds containing a porphyrin moiety and a metal atom. Ferroheme b is considered to be a practically insoluble (in water) and relatively neutral molecule. Ferroheme b may be a unique E.coli metabolite. Ferroheme b participates in a number of enzymatic reactions. In particular, Ferroheme b can be biosynthesized from protoporphyrin ix and fe2+; which is mediated by the enzyme ferrochelatase. In addition, Ferroheme b and farnesyl pyrophosphate can be converted into heme O; which is mediated by the enzyme heme O synthase.
53356674
[Fe].CC1=C(CCC([O-])=O)C2=N\C\1=C/C1=C(C=C)C(C)=C([N-]1)\C=C1/[N-]\C(=C/C3=N/C(=C\2)/C(CCC([O-])=O)=C3C)C(C)=C1C=C
C34H30FeN4O4
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);/p-4/b25-13-,26-13-,27-14-,28-15-,29-14-,30-15-,31-16-,32-16-;
RNQMHXMGXVQRMV-RGGAHWMASA-J
5,9-bis(2-carboxylatoethyl)-14,19-diethenyl-4,10,15,20-tetramethyl-21,22,23,24-tetraazapentacyclo[16.2.1.1³,⁶.1⁸,¹¹.1¹³,¹⁶]tetracosa-1,3(24),4,6,8(23),9,11,13,15,17,19-undecaene-21,22-diide iron
614.485
614.163836
-4.07
0
5,9-bis(2-carboxylatoethyl)-14,19-diethenyl-4,10,15,20-tetramethyl-21,22,23,24-tetraazapentacyclo[16.2.1.1³,⁶.1⁸,¹¹.1¹³,¹⁶]tetracosa-1,3(24),4,6,8(23),9,11,13,15,17,19-undecaene-21,22-diide iron
-4
-2
Protoheme ix, ferroprotoporphyrin ix
PW_C042924
FB
6585
109
7007
189
42789
317
35
Ammonia
HMDB0000051
Ammonia is a colourless alkaline gas and is one of the most abundant nitrogen-containing compounds in the atmosphere. It is an irritant with a characteristic pungent odor that is widely used in industry. Inasmuch as ammonia is highly soluble in water and, upon inhalation, is deposited in the upper airways, occupational exposures to ammonia have commonly been associated with sinusitis, upper airway irritation, and eye irritation. Acute exposures to high levels of ammonia have also been associated with diseases of the lower airways and interstitial lung. Small amounts of ammonia are naturally formed in nearly all tissues and organs of the vertebrate organism. Ammonia is both a neurotoxin and a metabotoxin. In fact, it is the most common endogenous neurotoxin. A neurotoxin is a compound that causes damage to neural tissue and neural cells. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Ammonia is recognized to be central in the pathogenesis of a brain condition known as hepatic encephalopathy, which arises from various liver diseases and leads to a build up ammonia in the blood (hyperammonemia). More than 40% of people with cirrhosis develop hepatic encephalopathy. Part of the neurotoxicity of ammonia arises from the fact that it easily crosses the blood-brain barrier and is absorbed and metabolized by the astrocytes, a population of cells in the brain that constitutes 30% of the cerebral cortex. Astrocytes use ammonia when synthesizing glutamine from glutamate. The increased levels of glutamine lead to an increase in osmotic pressure in the astrocytes, which become swollen. There is increased activity of the inhibitory gamma-aminobutyric acid (GABA) system, and the energy supply to other brain cells is decreased. This can be thought of as an example of brain edema. The source of the ammonia leading to hepatic encephalopathy is not entirely clear. The gut produces ammonia, which is metabolized in the liver, and almost all organ systems are involved in ammonia metabolism. Colonic bacteria produce ammonia by splitting urea and other amino acids, however this does not fully explain hyperammonemia and hepatic encephalopathy. The alternative explanation is that hyperammonemia is the result of the intestinal breakdown of amino acids, especially glutamine. The intestines have significant glutaminase activity, predominantly located in the enterocytes. On the other hand, intestinal tissues only have a little glutamine synthetase activity, making it a major glutamine-consuming organ. In addition to the intestine, the kidney is an important source of blood ammonia in patients with liver disease. Ammonia is also taken up by the muscle and brain in hepatic coma, and there is confirmation that ammonia is metabolized in muscle. Excessive formation of ammonia in the brains of Alzheimer's disease patients has also been demonstrated, and it has been shown that some Alzheimer's disease patients exhibit elevated blood ammonia concentrations. Ammonia is the most important natural modulator of lysosomal protein processing. Indeed, there is strong evidence for the involvement of aberrant lysosomal processing of beta-amyloid precursor protein (beta-APP) in the formation of amyloid deposits. Inflammatory processes and activation of microglia are widely believed to be implicated in the pathology of Alzheimer's disease. Ammonia is able to affect the characteristic functions of microglia, such as endocytosis, and cytokine production. Based on these facts, an ammonia-based hypothesis for Alzheimer's disease has been suggested (PMID: 17006913, 16167195, 15377862, 15369278). Chronically high levels of ammonia in the blood are associated with nearly twenty different inborn errors of metabolism including: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, 3-methyl-crotonylglycinuria, argininemia, argininosuccinic aciduria, beta-ketothiolase deficiency, biotinidase deficiency, carbamoyl phosphate synthetase deficiency, carnitine-acylcarnitine translocase deficiency, citrullinemia type I, hyperinsulinism-hyperammonemia syndrome, hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, isovaleric aciduria, lysinuric protein intolerance, malonic aciduria, methylmalonic aciduria, methylmalonic aciduria due to cobalamin-related disorders, propionic acidemia, pyruvate carboxylase deficiency, and short chain acyl CoA dehydrogenase deficiency (SCAD deficiency). Many of these inborn errors of metabolism are associated with urea cycle disorders or impairment of amino acid metabolism. High levels of ammonia in the blood (hyperammonemia) lead to the activation of NMDA receptors in the brain. This results in the depletion of brain ATP, which in turn leads to the release of glutamate. Ammonia also leads to the impairment of mitochondrial function and calcium homeostasis, thereby decreasing ATP synthesis. Excess ammonia also increases the formation of nitric oxide (NO), which in turn reduces the activity of glutamine synthetase, and thereby decreases the elimination of ammonia in the brain (PMID: 12020609). As a neurotoxin, ammonia predominantly affects astrocytes. Disturbed mitochondrial function and oxidative stress, factors implicated in the induction of the mitochondrial permeability transition, appear to be involved in the mechanism of ammonia neurotoxicity. Ammonia can also affect the glutamatergic and GABAergic neuronal systems, the two prevailing neuronal systems of the cortical structures. All of these effects can lead to irreversible brain damage, coma, and/or death. Infants with urea cycle disorders and hyperammonemia initially exhibit vomiting and increasing lethargy. If untreated, seizures, hypotonia (poor muscle tone, floppiness), respiratory distress (respiratory alkalosis), and coma can occur. Adults with urea cycle disorders and hyperammonemia will exhibit episodes of disorientation, confusion, slurred speech, unusual and extreme combativeness or agitation, stroke-like symptoms, lethargy, and delirium. Ammonia also has toxic effects when an individual is exposed to ammonia solutions. Acute exposure to high levels of ammonia in air may be irritating to skin, eyes, throat, and lungs and cause coughing and burns. Lung damage and death may occur after exposure to very high concentrations of ammonia. Swallowing concentrated solutions of ammonia can cause burns in the mouth, throat, and stomach. Splashing ammonia into eyes can cause burns and even blindness.
7664-41-7
C00014
222
16134
AMMONIA
217
N
H3N
InChI=1S/H3N/h1H3
QGZKDVFQNNGYKY-UHFFFAOYSA-N
ammonia
17.0305
17.026549101
1
ammonia
0
1
FDB003908
Ammonia anhydrous;Ammonia inhalant;Ammonia solution strong [usan];Ammonia water;Ammoniak;Liquid ammonia;Am-fol;Ammonia;Ammonia (conc 20% or greater);Ammonia gas;Ammonia solution;Ammonia solution strong (nf);Ammonia water (jp15);Ammoniac [french];Ammoniaca [italian];Ammoniacum gummi;Ammoniak [german];Ammoniak kconzentrierter;Ammoniakgas;Ammonium ion;Amoniak [polish];Anhydrous ammonia;Aromatic ammonia vaporole;Azane;Nh(3);Nh3;Nitro-sil;Primaeres amin;Sekundaeres amin;Spirit of hartshorn;Tertiaeres amin;[nh3];Ammoniac;Amoniaco;R-717;Ammonia solution strong
PW_C000035
NH3
97
9
112
5
133
8
142
4
438
2
479
13
550
14
1468
54
2533
22
2572
3
5338
111
6016
147
7022
160
7177
205
11786
198
11848
277
11885
215
12708
291
12718
292
76966
225
77046
294
77329
133
77343
132
77469
333
77499
113
77539
334
77597
115
77985
347
77993
112
78072
329
79244
293
80650
135
80657
119
116203
109
119921
122
120049
408
120053
126
120136
407
120343
406
120363
412
120462
405
121046
124
121161
425
122119
382
122800
374
122805
443
122993
120
123010
446
123096
376
123610
118
123733
460
124671
399
125311
297
125427
482
125431
301
125502
481
125663
479
125708
478
126102
299
126274
484
126966
502
126970
207
127039
206
127158
501
127200
209
127600
388
127837
389
6126
P-protein
P0A9J8
Involved in chorismate mutase activity. Chorismate = prephenate.
pheA
b2599
AP009048
3
5.4.99.5; 4.2.1.51
8685
101
7307
Branched-chain-amino-acid aminotransferase
P0AB80
Involved in catalytic activity. Acts on leucine, isoleucine and valine.
ilvE
b3770
AP009048
3
2.6.1.42
5824
Aspartate aminotransferase
P00509
Involved in transferase activity. L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate.
aspC
b0928
AP009048
3
2.6.1.1
8631
101
7090
Aromatic amino acid transport protein AroP
P15993
Involved in transport. Permease that is involved in the transport across the cytoplasmic membrane of the aromatic amino acids (phenylalanine, tyrosine, and tryptophan).
aroP
b0112
AP009048
3
8600
109
5871
Aromatic-amino-acid aminotransferase
P04693
Involved in transferase activity. An aromatic amino acid + 2-oxoglutarate = an aromatic oxo acid + L-glutamate.
tyrB
b4054
AP009048
3
2.6.1.57; 2.6.1.107
8684
101
7298
Inner membrane protein yddG
P46136
Carbohydrate transport and metabolism. Specific function unknown.
yddG
b1473
AP009048
3
8608
109
10125
Uncharacterized protein YbjE
P75826
ybjE
25
8620
234
6328
Catalase-peroxidase
P13029
Involved in catalase activity. Bifunctional enzyme with both catalase and broad- spectrum peroxidase activity. Displays also NADH oxidase, INH lyase and isonicotinoyl-NAD synthase activity.
katG
b3942
AP009048
3
1.11.1.21
6180
Cytochrome c-552
P0ABK9
Involved in nitrogen compound metabolic process. Plays a role in nitrite reduction.
nrfA
b4070
AP009048
3
1.7.2.2
8528
232
113396
94
5996
D-amino acid dehydrogenase small subunit
P0A6J5
Involved in D-amino-acid dehydrogenase activity. Oxidative deamination of D-amino acids.
dadA
b1189
AP009048
3
1.4.99.1
5895
95
8566
109
1477
chorismate mutase:pheA
3
PW_P001477
1738
6126
2
1478
phenylalanine transaminase:ilvE
3
PW_P001478
1739
7307
6
1479
phenylalanine transaminase:aspC
3
PW_P001479
1740
5824
2
1450
aromatic amino acid:H+ symporter AroP
3
PW_P001450
1698
7090
3688
phenylalanine aminotransferase
3
PW_P003688
10574
5871
2
506
1148
3689
aromatic amino acid exporter
3
PW_P003689
10575
7298
3690
Transporter: L-amino acid efflux transporter
3
PW_P003690
10576
10125
3691
Catalase Peroxidase
3
PW_P003691
10577
6328
4
507
42924
1169
cytochrome c nitrite reductase
3
PW_P001169
1352
6180
1378
D-amino acid dehydrogenase
3
PW_P001378
1607
5996
2
2859
false
PW_R002859
Right
11342
7748
1
Compound
false
11343
7823
1
Compound
false
2819
1477
5.4.99.5
2860
false
PW_R002860
Right
11344
7823
1
Compound
false
11345
40034
1
Compound
false
11346
1316
1
Compound
false
11347
1420
1
Compound
false
11348
131
1
Compound
false
2820
1477
3456
false
PW_R003456
Both
13846
104
1
Compound
false
13847
1065
1
Compound
false
13848
134
1
Compound
false
13849
131
1
Compound
false
3432
3688
2.6.1.57
3458
false
PW_R003458
Both
13856
104
1
Compound
false
13857
1065
1
Compound
false
13858
1316
1
Compound
false
13859
6723
1
Compound
false
3434
3691
1.11.1.21
2861
false
PW_R002861
Right
11349
131
1
Compound
false
11350
95
1
Compound
false
11351
134
1
Compound
false
11352
104
1
Compound
false
2821
1478
2.6.1.42
2822
1479
2.6.1.1
3457
false
PW_R003457
Both
13850
131
1
Compound
false
13851
35
1
Compound
false
13852
1169
1
ProteinComplex
false
13853
42923
1
Compound
false
13854
1420
1
Compound
false
13855
1169
1
ProteinComplex
false
3433
1378
1.4.99.1
357
PW_T000357
Active
413
104
1
Compound
107
108
Right
414
40034
1
Compound
107
108
Right
303
1450
2015-03-10T16:12:04-06:00
2015-03-10T16:12:04-06:00
109
427
PW_T000427
525
42923
1
Compound
108
107
Right
370
3689
2015-06-04T09:36:20-06:00
2015-06-04T09:36:20-06:00
109
428
PW_T000428
526
104
1
Compound
108
107
Right
371
3690
2015-06-04T09:40:54-06:00
2015-06-04T09:40:54-06:00
109
20485
7748
3
false
2144
965
10
regular
100
100
20486
7823
3
false
1759
965
10
regular
100
100
20487
40034
55
false
1661
1086
10
regular
78
78
20488
1316
52
false
1287
1091
10
regular
78
78
20489
1420
49
false
1390
1091
10
regular
78
78
20490
131
3
false
1188
960
10
regular
100
110
20491
95
3
false
1068
870
10
regular
100
110
20492
134
3
false
773
1110
10
regular
100
110
20494
104
107
3
false
209
1515
10
regular
100
100
20495
104
108
3
false
914
1520
10
regular
100
100
20496
40034
107
55
false
304
1625
10
regular
78
78
20497
40034
108
55
false
660
1625
10
regular
78
78
20498
1065
65
false
1070
1852
10
regular
78
78
20499
134
3
false
1389
1845
10
regular
100
110
20500
131
3
false
1509
1730
10
regular
100
110
20501
1148
9
false
1244
1733
10
regular
100
35
20503
42923
3
false
628
619
10
regular
100
100
20505
42923
107
3
false
248
619
10
regular
100
100
20506
104
107
3
false
914
2110
10
regular
100
100
20508
1065
65
false
1097
1461
10
regular
78
78
20509
1316
52
false
1392
1460
10
regular
78
78
20510
6723
3
false
1486
1513
10
regular
100
110
20511
42924
9
false
1241
1531
10
regular
100
25
25982
35
63
false
1184
552
10
regular
78
78
25984
1420
49
false
864
546
10
regular
78
78
9882
6126
101
6
false
1929
975
8
subunit
regular
160
80
9883
6126
101
6
false
1489
972
8
subunit
regular
160
80
9884
7307
17
false
873
975
8
subunit
regular
180
85
9885
5824
101
6
false
963
1017
8
subunit
regular
160
80
9886
7090
109
76
false
409
1529
8
subunit
regular
150
70
9887
5871
101
6
false
1209
1743
8
subunit
regular
160
80
9889
7298
109
76
false
408
634
8
subunit
regular
150
70
9890
10125
234
76
false
889
1985
8
subunit
regular
150
70
9891
6328
8
false
1221
1531
8
subunit
regular
140
85
12507
6180
232
2
false
1278
700
8
subunit
regular
150
70
12508
6180
232
2
false
768
709
8
subunit
regular
150
70
12509
5996
109
6
false
983
628
8
subunit
regular
160
80
7821
1477
669
9692
9882
7822
1477
669
9693
9883
7823
1478
669
9694
9884
7824
1479
669
9695
9885
7825
1450
669
9696
9886
7826
3688
669
9697
9887
2952
20501
30607
Cofactor
7828
3689
669
9699
9889
7829
3690
669
9700
9890
7830
3691
669
9701
9891
2953
20511
30622
Cofactor
9506
1169
669
12264
12507
9507
1169
669
12265
12508
9508
1378
669
12266
12509
30587
M2144 1015 C2127 1016 2107 1015 2089 1015
5
false
18
30588
M1859 1015 C1897 1015 1903 1015 1929 1015
5
false
18
true
M 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345
false
30589
M1759 1015 C1734 1014 1701 1014 1649 1012
5
false
18
30590
M1700 1086 C1699 1046 1682 1011 1649 1012
5
false
18
30591
M1326 1091 C1325 1032 1399 1011 1489 1012
5
false
18
true
M 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345
false
30592
M1429 1091 C1427 1059 1438 1013 1489 1012
5
false
18
true
M 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345
false
30593
M1288 1015 C1335 1015 1462 1011 1489 1012
5
false
18
true
M 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345
false
30599
M309 1565 C339 1565 379 1564 409 1564
83
false
18
30600
M914 1570 C884 1570 589 1564 559 1564
83
false
18
true
M 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345
false
30601
M343 1625 C346 1593 357 1565 409 1564
83
false
18
30602
M699 1625 C700 1580 640 1565 559 1564
83
false
18
true
M 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345
false
30603
M1014 1570 C1015 1644 1017 1687 1015 1785 C1091 1784 1139 1783 1209 1783
5
false
18
true
M 716.9468550441649 1998.261556296296 L 702 1997 L 708.3808877211858 2010.5751343230784
false
30604
M1109 1852 C1111 1808 1153 1784 1209 1785
5
false
18
true
M 716.9468550441649 1998.261556296296 L 702 1997 L 708.3808877211858 2010.5751343230784
false
30605
M1439 1845 C1438 1808 1436 1786 1371 1787
5
false
18
true
M 716.9468550441649 1998.261556296296 L 702 1997 L 708.3808877211858 2010.5751343230784
false
30606
M1509 1785 C1479 1785 1400 1786 1370 1786
5
false
18
true
M 716.9468550441649 1998.261556296296 L 702 1997 L 708.3808877211858 2010.5751343230784
false
30607
M1024 1993 L1024 2043 L1074 1993 z
10
true
18
30614
M628 669 C603 669 581 669 558 669
83
false
18
true
M 639.9903810567666 606.5 L 627 614 L 639.9903810567666 621.5
false
30615
M348 669 C371 669 388 670 408 669
83
false
18
true
M 1287.9468550441647 1498.261556296296 L 1273 1497 L 1279.380887721186 1510.5751343230784
false
30616
M964 1620 C964 1650 964 1955 964 1985
83
false
18
30617
M964 2110 C964 2080 964 2085 964 2055
83
false
18
true
M 482.94685504416486 1898.261556296296 L 468 1897 L 474.38088772118584 1910.5751343230784
false
30622
M1221 1946 L1221 1996 L1271 1946 z
10
true
18
3659545
M1014 1570 C1044 1570 1191 1571 1221 1571
5
false
18
true
M 25.946855044164835 856.261556296296 L 11 855 L 17.380887721185843 868.5751343230784
false
3659546
M1136 1539 C1137 1564 1191 1571 1221 1571
5
false
18
true
M 25.946855044164835 856.261556296296 L 11 855 L 17.380887721185843 868.5751343230784
false
3659547
M1431 1538 C1432 1570 1391 1571 1361 1571
5
false
18
true
M 25.946855044164835 856.261556296296 L 11 855 L 17.380887721185843 868.5751343230784
false
3659548
M1486 1568 C1456 1568 1391 1571 1361 1571
5
false
18
true
M 25.946855044164835 856.261556296296 L 11 855 L 17.380887721185843 868.5751343230784
false
3659549
M1188 1015 C1146 1015 1102 1015 1053 1015
5
false
18
3659550
M1118 980 C1118 998 1094 1014 1053 1015
5
false
18
3659551
M873 1165 C968 1166 963 1090 963 1060
5
false
18
true
M 25.946855044164835 634.261556296296 L 11 633 L 17.380887721185843 646.5751343230784
false
3659552
M964 1520 C964 1490 963 1087 963 1057
5
false
18
true
M 25.946855044164835 634.261556296296 L 11 633 L 17.380887721185843 646.5751343230784
false
3659553
M1014 1570 C1015 1481 1014 1343 1015 1299 C1067 1299 1098 1299 1144 1300
5
false
18
3659566
M1238 960 C1240 895 1222 668 1143 668
5
false
18
true
M 25.946855044164835 856.261556296296 L 11 855 L 17.380887721185843 868.5751343230784
false
3659567
M1223 630 C1224 654 1218 668 1143 668
5
false
18
true
M 25.946855044164835 856.261556296296 L 11 855 L 17.380887721185843 868.5751343230784
false
3659568
M728 669 C698 669 1013 668 983 668
5
false
18
true
M 25.946855044164835 856.261556296296 L 11 855 L 17.380887721185843 868.5751343230784
false
3659569
M903 624 C903 658 932 667 983 668
5
false
18
true
M 25.946855044164835 856.261556296296 L 11 855 L 17.380887721185843 868.5751343230784
false
3659570
M1353 700 C1352 664 1176 667 1143 668
5
false
18
true
M 25.946855044164835 856.261556296296 L 11 855 L 17.380887721185843 868.5751343230784
false
3659571
M843 709 C843 672 1013 668 983 668
5
false
18
true
M 25.946855044164835 856.261556296296 L 11 855 L 17.380887721185843 868.5751343230784
false
3659630
M2194 965 C2196 934 2193 863 2194 827
5
false
18
5390
669
2859
19367
20485
30587
Left
19368
20486
30588
Right
5581
2819
7821
5391
669
2860
19369
20486
30589
Left
19370
20487
30590
Left
19371
20488
30591
Right
19372
20489
30592
Right
19373
20490
30593
Right
5582
2820
7822
5393
669
3456
19378
20495
30603
Left
19379
20498
30604
Left
19380
20499
30605
Right
19381
20500
30606
Right
5585
3432
7826
797519
669
3458
3223302
20495
3659545
Left
3223303
20508
3659546
Left
3223304
20509
3659547
Right
3223305
20510
3659548
Right
753182
3434
7830
797520
669
2861
3223306
20490
3659549
Left
3223307
20491
3659550
Left
3223308
20492
3659551
Right
3223309
20495
3659552
Right
753183
2822
7824
753184
2821
7823
797523
669
3457
3223318
20490
3659566
Left
3223319
25982
3659567
Left
3223320
20503
3659568
Right
3223321
25984
3659569
Right
18640
9506
3659570
Left
18641
9507
3659571
Right
753187
3433
9508
727
357
669
1691
20494
30599
Left
1692
20495
30600
Right
1693
20496
30601
Left
1694
20497
30602
Right
512
7825
303
728
427
669
1695
20503
30614
Left
1696
20505
30615
Right
513
7828
370
729
428
669
1697
20495
30616
Left
1698
20506
30617
Right
514
7829
371
109456
109785
669
14
false
1144
1265
16
regular
106152
20495
3659553
Left
109467
109795
669
14
false
2119
757
16
regular
106163
20485
3659630
Right
186383
1585
1100
1.6
1.6
0
2
92
479
481
1246
M125 225 C125 175 175 125 225 125 C953 125 1901 125 2629 125 C2679 125 2729 175 2729 225 C2729 847 2729 1655 2729 2277 C2729 2327 2679 2377 2629 2377 C1901 2377 953 2377 225 2377 C175 2377 125 2327 125 2277 C125 1655 125 847 125 225
1
true
6
2604.0
2252.0
1247
M477 575 C477 525 527 475 577 475 C1092 475 1763 475 2278 475 C2328 475 2378 525 2378 575 C2378 984 2378 1515 2378 1924 C2378 1974 2328 2024 2278 2024 C1763 2024 1092 2024 577 2024 C527 2024 477 1974 477 1924 C477 1515 477 984 477 575
1
true
6
1901.0
1549.0