Information on EC 1.14.13.39 - nitric-oxide synthase (NADPH)

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
1.14.13.39
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RECOMMENDED NAME
GeneOntology No.
nitric-oxide synthase (NADPH)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2 L-arginine + 2 NADPH + 2 H+ + 2 O2 = 2 Nomega-hydroxy-L-arginine + 2 NADP+ + 2 H2O
show the reaction diagram
(1a)
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2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
show the reaction diagram
2 Nomega-hydroxy-L-arginine + NADPH + H+ + 2 O2 = 2 L-citrulline + 2 nitric oxide + NADP+ + 2 H2O
show the reaction diagram
(1b)
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
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redox reaction
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reduction
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
nitric oxide biosynthesis II (mammals)
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Arginine biosynthesis
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Arginine and proline metabolism
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Cyanoamino acid metabolism
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Metabolic pathways
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Biosynthesis of secondary metabolites
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Biosynthesis of antibiotics
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SYSTEMATIC NAME
IUBMB Comments
L-arginine,NADPH:oxygen oxidoreductase (nitric-oxide-forming)
The enzyme consists of linked oxygenase and reductase domains. The eukaryotic enzyme binds FAD, FMN, heme (iron protoporphyrin IX) and tetrahydrobiopterin, and its two domains are linked via a regulatory calmodulin-binding domain. Upon calcium-induced calmodulin binding, the reductase and oxygenase domains form a complex, allowing electrons to flow from NADPH via FAD and FMN to the active center. The reductase domain of the enzyme from the bacterium Sorangium cellulosum utilizes a [2Fe-2S] cluster to transfer the electrons from NADPH to the active center. cf. EC 1.14.14.47, nitric-oxide synthase (flavodoxin).
CAS REGISTRY NUMBER
COMMENTARY hide
125978-95-2
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
shelf fungus, collected from forest in Darjeeling, East Sikkim, India
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
constitutive enzyme
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
hybrid tilapia, three isozymes eNOS, iNOS and nNOS
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
neuronal isoform
UniProt
Manually annotated by BRENDA team
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1,4-bis-[[2-(dimethylamino-N-oxide)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione + NADPH
1-[[2-(dimethylamino-N-oxide)ethyl]amino]-4-[[2-(dimethylamino)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione + ?
show the reaction diagram
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ir
1-butyl-2-hydroxyguanidine + NADPH + O2
? + NO + NADP+
show the reaction diagram
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?
1-[[2-(dimethylamino-N-oxide)ethyl]amino]-4-[[2-(dimethylamino)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione + NADPH
1,4-bis[[2-(dimethylamino)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione + ?
show the reaction diagram
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ir
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
show the reaction diagram
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?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
show the reaction diagram
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
show the reaction diagram
2,6-dichlorophenolindophenol + NADPH + O2
? + NO + NADP+
show the reaction diagram
2-hydroxy-1-(4-hydroxyphenyl)guanidine + NADPH + O2
? + NO + NADP+
show the reaction diagram
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?
2-hydroxy-1-isopropylguanidine + NADPH + O2
? + NO + NADP+
show the reaction diagram
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?
adriamycin + NADPH + O2
? + NO + NADP+
show the reaction diagram
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?
ferricyanide + NADPH + O2
ferrocyanide + NADP+ + H2O
show the reaction diagram
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?
ferricyanide + NADPH + O2
ferrocyanide + NO + NADP+
show the reaction diagram
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?
ferricytochrome c + NADPH + O2
ferrocytochrome c + NO + NADP+
show the reaction diagram
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?
L-Ala-L-Arg + NADPH + O2
?
show the reaction diagram
L-Arg-L-Arg + NADPH + O2
?
show the reaction diagram
L-Arg-L-Arg-L-Arg + NADPH + O2
?
show the reaction diagram
L-Arg-L-Phe + NADPH + O2
?
show the reaction diagram
L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
show the reaction diagram
L-arginine + H2O2 + tetrahydrobiopterin
? + NO + NADP+
show the reaction diagram
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?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
show the reaction diagram
L-arginine + NADPH + H+ + O2
Nomega-hydroxy-L-arginine + NADP+ + H2O
show the reaction diagram
L-arginine + NADPH + O2 + tetrahydrobiopterin
citrulline + NO + NADP+ + ?
show the reaction diagram
L-homoarginine + NADPH + O2
?
show the reaction diagram
menadione + NADPH + O2
? + NO + NADP+
show the reaction diagram
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?
mitomycin c + NADPH + O2
? + NO + NADP+
show the reaction diagram
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?
N-hydroxy-L-arginine + H2O2 + tetrahydrobiopterin
? + NADP+
show the reaction diagram
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?
N-hydroxy-L-arginine + NADPH + O2
? + NO + NADP+
show the reaction diagram
Ngamma-hydroxy-L-arginine + H2O2
citrulline + Ndelta-cyanoornithine + NO2- + NO3-
show the reaction diagram
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tetrahydrobiopterin-free
NO2-/NO3- as aerobic decomposition products from NO-
?
Ngamma-hydroxy-L-arginine + NADPH + O2
citrulline + NADP+ + NO
show the reaction diagram
nitroblue tetrazolium + NADPH
nitroblue tetrazolium-flavazone + NADP+
show the reaction diagram
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
show the reaction diagram
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
L-citrulline + NADP+ + NO + H2O
show the reaction diagram
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second half reaction
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?
oxidized cytochrome c + NADPH + O2
reduced cytochrome c + NADP+ + H2O
show the reaction diagram
peroxynitrite + 4-hydroxyphenylacetic acid + NADPH + H+
4-hydroxyl-3-nitro-phenylacetic acid + NADP+ + H2O
show the reaction diagram
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oxidation and nitration, although H4B binding seems unable to affect iNOSoxy capacity to activate peroxynitrite decomposition, the binding of Arg and citrulline at the distal side of the heme pocket drastically reduces peroxynitrite activation
product dimers
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additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
show the reaction diagram
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
show the reaction diagram
L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
show the reaction diagram
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
show the reaction diagram
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(6R)-5,6,7,8-tetrahydro-L-biopterin
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(6R)-tetrahydrobiopterin
2',3'-dialdehyde analogue of NADPH
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activation, can substitute for NADPH at low concentrations, inhibitory at concentrations of 40times the apparent Km-value or after prolonged incubation
2,6-dichlorophenolindophenol
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activation
5,6,7,8-tetrahydro-L-biopterin
Calmodulin
cytochrome c
flavodoxin
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reduced YkuN and YkuP containing FMN, YkuN is more efficient in supporting bsNOS catalysis, Km for YkuN is 0.0016 mM, for YkuP 0.022 mM, overview
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flavodoxin I
binding site sequence, overview
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heme b
NADP+
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binding mechanism
nitroblue tetrazolium
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activation
tetrahydrobiopterin
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+/calmodulin
Mg2+
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activates both isozymes
O2
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oxygen tension influences the activity
Zinc
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0.43 mol per mol of subunit
Zn2+
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bound by Cys104, Cys109, and Cys194 of isozyme iNOS oxygenase domain