Original Literature | Model OverView |
---|---|
Publication
Title
Regulation of nitric oxide synthesis and apoptosis by arginase and argininerecycling.
Affiliation
Laboratory of Molecular Genetics, Faculty of Pharmaceutical Sciences, SojoUniversity, Kumamoto 860-0082, Japan. mori-m@ph.sojo-u.ac.jp
Abstract
Nitric oxide (NO) is synthesized from arginine and O2 by NO synthase (NOS).Citrulline formed as a by-product of the NOS reaction can be recycled toarginine by argininosuccinate synthetase (AS) and argininosuccinate lyase (AL).We found that AS and sometimes AL are coinduced with inducible NOS (iNOS) invarious cells. In these cells, NO was synthesized from citrulline (via arginine)as well as from arginine, indicating operation of the citrulline-NO cycle. Onthe other hand, we found that arginase isoforms (types I and II) are coinducedwith iNOS by LPS in rodent tissues and cultured macrophages. Km values forarginine of arginase I and II (approximately 10 mmol/L) are much higher thanthat of iNOS (approximately 5 micromol/L), whereas Vmax of arginase I and IIwere 10(3)-10(4) times higher than that of iNOS in activated macrophages. Thus,Vmax/Km values of arginases were close to that of iNOS, and these enzymes wereexpected to compete for arginine in the cells. In fact, NO production by iNOS inactivated macrophages was decreased by coinduction of arginase I or arginase II.Low concentrations of NO protect cells from apoptosis, whereas excessive NOcauses apoptosis. We found that NO causes endoplasmic reticulum (ER) stress,induces a transcription factor, CAAT/enhancer binding protein (C/EBP) homologousprotein (CHOP), and leads to apoptosis. These results suggest that the argininemetabolic enzymes and the ER stress-CHOP pathway can be good targets to regulateNO production and NO-mediated apoptosis in diseases associated withoverproduction or impaired production of NO.
PMID
17513437
|
Entity
GRP78
--
MO000006117
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m746
10
infinite
0
InterPro | IPR000886 |
TRANSPATH | MO000006117 |
--
iNOS
--
MO000021201
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m5576
10
infinite
0
TRANSPATH | MO000021201 |
--
Hsp70
--
MO000021614
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m5956
10
infinite
0
InterPro | IPR001023 |
TRANSPATH | MO000021614 |
--
glucocorticoids
--
MO000021732
cso30:c:Protein
cso30:i:CC_CellComponent
--
--
csml-variable:Double
m6069
10
infinite
0
TRANSPATH | MO000021732 |
--
argininosuccinate lyase
--
MO000068737
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m43582
10
infinite
0
TRANSPATH | MO000068737 |
--
argininosuccinate synthase
--
MO000089591
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m63193
10
infinite
0
TRANSPATH | MO000089591 |
--
arginase
--
MO000089992
cso30:c:Protein
cso30:i:CC_CellComponent
--
csml-variable:Double
m63554
10
infinite
0
TRANSPATH | MO000089992 |
--
--
e1
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane
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--
--
csml-variable:Double
m1
0
infinite
0
--
TNF-alphaR
--
e10
cso30:c:Protein
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m10
0
infinite
0
--
Urea
--
e11
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
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--
csml-variable:Double
m11
0
infinite
0
--
ornithine
--
e12
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
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--
csml-variable:Double
m12
0
infinite
0
--
NH3
--
e13
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m13
0
infinite
0
--
CO2
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e14
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m14
0
infinite
0
--
Ornithine
--
e15
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m15
0
infinite
0
--
carbamylphosphate cynthase I
--
e16
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m16
0
infinite
0
--
ornithine transcarbamylase
--
e17
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m17
0
infinite
0
--
LPS receptor
--
e18
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m18
0
infinite
0
--
LPS:Receptor
--
e19
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m19
0
infinite
0
--
--
e2
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m2
0
infinite
0
--
Argininosuccinate synthase
--
e20
cso30:c:mRNA
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m20
0
infinite
0
--
Argininisuccinate lyase
--
e21
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
--
csml-variable:Double
m21
0
infinite
0
--
NO
--
e22
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
--
csml-variable:Double
m22
0
infinite
0
--
Glucocorticoid Receptor
--
e23
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m23
0
infinite
0
--
Glucocorticoids:Receptor
--
e24
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m24
0
infinite
0
--
csml-variable:Double
m25
0
infinite
0
--
Arginase I
--
e26
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
csml-variable:Double
m26
0
infinite
0
--
IL-4:IL-4R
--
e27
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m27
0
infinite
0
--
IL-13:IL-13R
--
e28
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m28
0
infinite
0
--
arginase II
--
e29
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
csml-variable:Double
m29
0
infinite
0
--
--
e3
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_
--
--
--
csml-variable:Double
m3
0
infinite
0
--
arginase II
--
e30
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m30
0
infinite
0
--
Ligand:LXRs
--
e31
cso30:c:Complex
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m31
0
infinite
0
--
Arginase I
--
e32
cso30:c:Protein
cso30:i:CC_Cytosol
--
csml-variable:Double
m32
0
infinite
0
--
IFNgammaR
--
e33
cso30:c:Protein
cso30:i:CC_Cytosol
--
--
csml-variable:Double
m33
0
infinite
0
--
IFNgamma:IFNgammaR
--
e34
cso30:c:Complex
cso30:i:CC_Cytosol
--
csml-variable:Double
m34
0
infinite
0
--
dexamethasone
--
e35
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
--
csml-variable:Double
m35
0
infinite
0
--
Dibutyryl CAMP
--
e36
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
--
csml-variable:Double
m36
0
infinite
0
--
Hsp70
--
e37
cso30:c:mRNA
cso30:i:CC_Nucleoplasm
--
--
csml-variable:Double
m37
0
infinite
0
--
TNF_alpha:TNF-alphaR
--
e38
cso30:c:Complex
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m38
0
infinite
0
--
SNAP
--
e39
cso30:c:SmallMolecule
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m39
0
infinite
0
--
--
e4
cso30:c:EntityBiologicalCompartment
cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_
--
--
--
csml-variable:Double
m4
0
infinite
0
--
DjA1
--
e40
cso30:c:mRNA
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m40
0
infinite
0
--
DjA1
--
e41
cso30:c:Protein
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m41
0
infinite
0
--
DjB1
--
e42
cso30:c:mRNA
cso30:i:CC_Cytoplasm
--
--
csml-variable:Double
m42
0
infinite
0
--
DjB1
--
e43
cso30:c:Protein
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m43
0
infinite
0
--
CHOP
--
e44
cso30:c:mRNA
cso30:i:CC_Extracellular
--
csml-variable:Double
m44
0
infinite
0
--
CHOP
--
e45
cso30:c:Protein
cso30:i:CC_Cytoplasm
--
csml-variable:Double
m45
0
infinite
0
--
citrulline
--
e5
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
--
csml-variable:Double
m5
0
infinite
0
--
--
e50
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearEnvelopeLumen
--
--
--
csml-variable:Double
m50
0
infinite
0
--
--
e51
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearPore
--
--
--
csml-variable:Double
m51
0
infinite
0
--
--
e52
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearInnerMembrane
--
--
--
csml-variable:Double
m52
0
infinite
0
--
--
e53
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearLumen
--
--
--
csml-variable:Double
m53
0
infinite
0
--
--
e54
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearOuterMembrane
--
--
--
csml-variable:Double
m54
0
infinite
0
--
--
e55
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleus
--
--
--
csml-variable:Double
m55
0
infinite
0
--
--
e56
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleoplasm
--
--
--
csml-variable:Double
m56
0
infinite
0
--
--
e57
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearBody
--
--
--
csml-variable:Double
m57
0
infinite
0
--
--
e58
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Nucleolus
--
--
--
csml-variable:Double
m58
0
infinite
0
--
--
e59
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearEnvelope
--
--
--
csml-variable:Double
m59
0
infinite
0
--
Arginine
--
e6
cso30:c:SmallMolecule
cso30:i:CC_Cytosol
--
csml-variable:Double
m6
0
infinite
0
--
--
e60
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Chromatin
--
--
--
csml-variable:Double
m60
0
infinite
0
--
--
e61
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearChromosome
--
--
--
csml-variable:Double
m61
0
infinite
0
--
--
e62
cso30:c:EntityBiologicalCompartment
cso30:i:CC_NuclearCentromere
--
--
--
csml-variable:Double
m62
0
infinite
0
--
--
e7
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell
--
--
--
csml-variable:Double
m7
0
infinite
0
--
--
e8
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cell_WithoutCellWall_
--
--
--
csml-variable:Double
m8
0
infinite
0
--
--
e9
cso30:c:EntityBiologicalCompartment
cso30:i:CC_Cytoplasm
--
--
--
csml-variable:Double
m9
0
infinite
0
--
p1
p1
cso30:i:ME_UnknownProduction
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c2 : 1
stoichiometry:c3 : 1
stoichiometry:c4 : 1
stoichiometry:c1 : 1
m5*m43582*m63193*0.1
nodelay
--
0
PMID: 17513437 Arginine is synthesized from citrulline by successive actions of argininosuccinate synthetase (AS) and argininosuccinate lyase (AL), the third and fourth enzymes of the urea cycle (ornithine cycle).
p10
p10
cso30:i:ME_UnknownProduction
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c64 : 1
stoichiometry:c77 : 1
stoichiometry:c78 : 1
stoichiometry:c57 : 1
m5*m5576*0.1
nodelay
--
0
PMID: 17513437,10592289 NO was produced from citrulline (via arginine) as well as from arginine in activated C6 cells and retinal pigment epithelial cells, indicating that the citrulline-NO cycle is actually functioning in these cells PMID: 17513437 When RAW264.7 cells are exposed to LPS and IFN-g, iNOS is induced, and NO production increases. PMID: 17513437, 9971738 When dexamethasone and dibutyryl cAMP are added, both iNOS and arginase II are induced, and NO production is much decreased PMID: 17513437 Thus, both cytosolic arginase I and mitochondrial arginase II are effective in down-regulating NO production and in preventing NO-mediated apoptosis in activated macrophages
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c32 : 1
stoichiometry:c33 : 1
stoichiometry:c34 : 1
m6069*m23*0.1
nodelay
--
0
PMID: 17513437 Transcription of the rat arginase I gene is induced by glucocorticoids in a delayed secondary manner.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1
stoichiometry:c35 : 1
stoichiometry:c36 : 1
m24*m25*0.1
nodelay
--
0
PMID: 17513437 Transcription of the rat arginase I gene is induced by glucocorticoids in a delayed secondary manner.
p13
p13
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c39 : 1
stoichiometry:c40 : 1
m1947*m1952*0.1
nodelay
--
0
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c42 : 1
stoichiometry:c41 : 1
m27*0.1
nodelay
--
0
PMID: 17523437 Arginase I expression is induced in macrophages by Th2 cytokines such as IL-4 and IL-13.
p13
p15
cso30:i:ME_Binding
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c44 : 1
stoichiometry:c45 : 1
stoichiometry:c46 : 1
m836*m12757*0.1
nodelay
--
0
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c43 : 1
stoichiometry:c50 : 1
stoichiometry:c47 : 1
m29*m31*0.1
nodelay
--
0
PMID: 17513437,16943198 Marathe et al. found that arginase II is induced in macrophages by the liver X receptors (LXRs) that have been implicated in lipid metabolism and inflammation
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c48 : 1
stoichiometry:c49 : 1
m28*0.1
nodelay
--
0
PMID: 17523437 Arginase I expression is induced in macrophages by Th2 cytokines such as IL-4 and IL-13.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c51 : 1
stoichiometry:c53 : 1
stoichiometry:c52 : 1
m29*m19*0.1
nodelay
--
0
PMID: 17513437,8898077,1731766,7507106 iNOS and arginase II are coinduced in LPS-stimulated RAW 264.7 macrophages
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c54 : 1
stoichiometry:c56 : 1
stoichiometry:c55 : 1
m26*m19*0.1
nodelay
--
0
PMID: 17513437,9013624 Surprisingly, however, we found that arginase I, not arginase II, is coinduced with iNOS in rat peritoneal macrophages and in vivo in rat lung after LPS treatment
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c5 : 1
stoichiometry:c7 : 1
stoichiometry:c6 : 1
m6*m63554*0.1
nodelay
--
0
PMID: 17513437 The major site of arginine metabolism in ureotelic animals is the liver, where arginine generated in the urea cycle is rapidly converted to urea and ornithine by arginase with no net synthesis of arginine PMID: 17513437 In contrast, arginine is hydrolyzed to urea and ornithine by arginase.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c59 : 1
stoichiometry:c60 : 1
m1639*m33*0.1
nodelay
--
0
PMID: 17513437 When RAW264.7 cells are exposed to LPS and IFN-g, iNOS is induced, and NO production increases.
p21
p21
cso30:i:ME_Translation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c61 : 1
stoichiometry:c63 : 1
stoichiometry:c62 : 1
m93479*m34*0.1
nodelay
--
0
PMID: 17513437 When RAW264.7 cells are exposed to LPS and IFN-g, iNOS is induced, and NO production increases.
p22
p22
cso30:i:ME_Translation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c65 : 1
stoichiometry:c67 : 1
stoichiometry:c66 : 1
m93479*m35*0.1
nodelay
--
0
PMID: 17513437, 9971738 When dexamethasone and dibutyryl cAMP are added, both iNOS and arginase II are induced, and NO production is much decreased
p22
p23
cso30:i:ME_Translation
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c70 : 1
stoichiometry:c68 : 1
m93479*m36*0.1
nodelay
--
0
PMID: 17513437, 9971738 When dexamethasone and dibutyryl cAMP are added, both iNOS and arginase II are induced, and NO production is much decreased
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c73 : 1
stoichiometry:c72 : 1
m29*m35*0.1
nodelay
--
0
PMID: 17513437, 9971738 When dexamethasone and dibutyryl cAMP are added, both iNOS and arginase II are induced, and NO production is much decreased
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c76 : 1
stoichiometry:c75 : 1
m29*m36*0.1
nodelay
--
0
PMID: 17513437, 9971738 When dexamethasone and dibutyryl cAMP are added, both iNOS and arginase II are induced, and NO production is much decreased
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c79 : 1
stoichiometry:c81 : 1
stoichiometry:c80 : 1
m37*m22*0.1
nodelay
--
0
PMID: 17513437,8995451 NO was reported to protect cultured hepatocytes from tumor necrosis factor-a-induced apoptosis by inducing heat shock protein 70 (Hsp70) PMID: 17513437 Among DnaJ homologs, which act as cochaperones of Hsp70, DjB1 was strongly induced, and DjA1 was weakly induced;
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c82 : 1
stoichiometry:c83 : 1
stoichiometry:c84 : 1
m230*m10*0.1
nodelay
--
0
PMID: 17513437,8995451 NO was reported to protect cultured hepatocytes from tumor necrosis factor-a-induced apoptosis by inducing heat shock protein 70 (Hsp70)
p28
p28
cso30:i:CE_ProgrammedCellDeath
cso30:i:CC_Cytoplasm
--
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c85 : 1
stoichiometry:c86 : 1
m38*0.1
nodelay
--
0
PMID: 17513437,8995451 NO was reported to protect cultured hepatocytes from tumor necrosis factor-a-induced apoptosis by inducing heat shock protein 70 (Hsp70)
p29
p29
cso30:i:CE_ProgrammedCellDeath
cso30:i:CC_Cytoplasm
--
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c87 : 1
stoichiometry:c88 : 1
stoichiometry:c91 : 1
stoichiometry:c94 : 1
m39*0.1
nodelay
--
0
PMID: 17513437 SNAP-induced apoptosis was prevented by coexpression of Hsp70 and DjB1 or DjA1.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c8 : 1
stoichiometry:c9 : 1
m19*m93479*0.1
nodelay
--
0
PMID: 17513437 When iNOS is induced in various cells stimulated by bacterial LPS and cytokines, AS and sometimes AL are coinduced. PMID: 17513437,8898077,1731766,7507106 iNOS and arginase II are coinduced in LPS-stimulated RAW 264.7 macrophages PMID: 17513437 When RAW264.7 cells are exposed to LPS and IFN-g, iNOS is induced, and NO production increases.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c89 : 1
stoichiometry:c90 : 1
m40*0.1
nodelay
--
0
PMID: 17513437 Among DnaJ homologs, which act as cochaperones of Hsp70, DjB1 was strongly induced, and DjA1 was weakly induced;
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c92 : 1
stoichiometry:c93 : 1
m42*0.1
nodelay
--
0
PMID: 17513437 Among DnaJ homologs, which act as cochaperones of Hsp70, DjB1 was strongly induced, and DjA1 was weakly induced;
PMID: 17513437 Overexpression of CHOP in RAW264.7 cells resulted in apoptosis.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c95 : 1
stoichiometry:c99 : 1
stoichiometry:c96 : 1
m44*m22*0.1
nodelay
--
0
PMID: 17513437,11591387 WhenRAW264.7 cellswere treated with LPS plus interferon-g or the NO donor SNAP, NO-mediated apoptosis occurred PMID: 17513437,11526215 We found that CHOP, a C/EBP family transcription factor that is involved in ER stress-induced apoptosis, is induced
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c101 : 1
stoichiometry:c102 : 1
stoichiometry:c103 : 1
m39*m44*0.1
nodelay
--
0
PMID: 17513437,11591387 WhenRAW264.7 cellswere treated with LPS plus interferon-g or the NO donor SNAP, NO-mediated apoptosis occurred PMID: 17513437,11526215 We found that CHOP, a C/EBP family transcription factor that is involved in ER stress-induced apoptosis, is induced
p35
p35
cso30:i:ME_Translation
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c105 : 1
stoichiometry:c106 : 1
stoichiometry:c107 : 1
stoichiometry:c108 : 1
stoichiometry:c104 : 1
m93206*m19*m34*m22*0.1
nodelay
--
0
PMID: 17513437 BiP/GRP78, an ER chaperone that is known to be induced by ER stress, was also induced. PMID: 17513437 WhenRAW264.7 cellswere treated with LPS plus interferon-g or the NO donor SNAP, NO-mediated apoptosis occurred
p35
p36
cso30:i:ME_Translation
cso30:i:CC_Cytoplasm
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c109 : 1
stoichiometry:c111 : 1
stoichiometry:c110 : 1
m93206*m39*0.1
nodelay
--
0
PMID: 17513437 BiP/GRP78, an ER chaperone that is known to be induced by ER stress, was also induced. PMID: 17513437 WhenRAW264.7 cellswere treated with LPS plus interferon-g or the NO donor SNAP, NO-mediated apoptosis occurred
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c112 : 1
stoichiometry:c114 : 1
m22*0.1
nodelay
--
0
PMID: 17513437 High concentrations of NO induce apoptosis by the DNA damage-p53 pathway PMID: 17513437 It is generally thought that NO induces DNA damage, leading to cell death through induction of p53.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c113 : 1
stoichiometry:c115 : 1
m93404*0.1
nodelay
--
0
PMID: 17513437 High concentrations of NO induce apoptosis by the DNA damage-p53 pathway PMID: 17513437 It is generally thought that NO induces DNA damage, leading to cell death through induction of p53.
p39
p39
cso30:i:CE_ProgrammedCellDeath
cso30:i:CC_Cytoplasm
--
--
PMID: 17513437 It is generally thought that NO induces DNA damage, leading to cell death through induction of p53.
p4
p4
cso30:i:ME_UnknownProduction
cso30:i:CC_Cytosol
--
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c11 : 1
stoichiometry:c12 : 1
stoichiometry:c13 : 1
stoichiometry:c15 : 1
stoichiometry:c16 : 1
stoichiometry:c14 : 1
m13*m14*m15*m16*m17*0.1
nodelay
--
0
PMID: 17513437 In adult animals, citrulline is produced primarily by the small intestine from NH3, CO2, and ornithine by carbamylphosphate synthetase I and ornithine transcarbamylase, the first 2 enzymes of the urea cycle, and is supplied to the kidney and probably to other tissues for synthesis of arginine.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c17 : 1
stoichiometry:c18 : 1
m6*0.1
nodelay
--
0
PMID: 17513437 Citrulline is also formed from arginine as a coproduct of NOS reaction, and this citrulline may be recycled to arginine if AS and AL are present in the same cell, forming the citrulline-NO cycle.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c19 : 1
stoichiometry:c21 : 1
stoichiometry:c20 : 1
m6*m63554*0.1
nodelay
--
0
PMID: 17513437 The major site of arginine metabolism in ureotelic animals is the liver, where arginine generated in the urea cycle is rapidly converted to urea and ornithine by arginase with no net synthesis of arginine PMID: 17513437 In contrast, arginine is hydrolyzed to urea and ornithine by arginase.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c22 : 1
stoichiometry:c23 : 1
m157177*m18*0.1
nodelay
--
0
PMID: 17513437 When iNOS is induced in various cells stimulated by bacterial LPS and cytokines, AS and sometimes AL are coinduced.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c25 : 1
stoichiometry:c27 : 1
stoichiometry:c26 : 1
m20*m19*0.1
nodelay
--
0
PMID: 17513437 When iNOS is induced in various cells stimulated by bacterial LPS and cytokines, AS and sometimes AL are coinduced.
--
and
mass
coefficient1:0.1
coefficient2:1.0
stoichiometry:c28 : 1
stoichiometry:c30 : 1
stoichiometry:c29 : 1
m21*m19*0.1
nodelay
--
0
PMID: 17513437 When iNOS is induced in various cells stimulated by bacterial LPS and cytokines, AS and sometimes AL are coinduced.
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:InputInhibitor
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--
cso30:c:OutputProcess
threshold
--
0
1,
--
cso30:c:InputAssociation
threshold
--
0
1,
--