EC               Enzyme                                 

nitric-oxide synthase (NADPH);
NOS (gene name);
nitric oxide synthetase (ambiguous);
endothelium-derived relaxation factor-forming enzyme;
endothelium-derived relaxing factor synthase;
NO synthase (ambiguous);
NADPH-diaphorase (ambiguous)
Acting on paired donors, with incorporation or reduction of molecular oxygen;
With NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor
BRITE hierarchy
L-arginine,NADPH:oxygen oxidoreductase (nitric-oxide-forming)
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O (overall reaction) [RN:R00557];
(1a) 2 L-arginine + 2 NADPH + 2 H+ + 2 O2 = 2 Nomega-hydroxy-L-arginine + 2 NADP+ + 2 H2O  [RN:R00558];
(1b) 2 Nomega-hydroxy-L-arginine + NADPH + H+ + 2 O2 = 2 L-citrulline + 2 nitric oxide + NADP+ + 2 H2O [RN:R00111]
L-arginine [CPD:C00062];
NADPH [CPD:C00005];
H+ [CPD:C00080];
O2 [CPD:C00007];
L-citrulline [CPD:C00327];
nitric oxide [CPD:C00533];
NADP+ [CPD:C00006];
H2O [CPD:C00001];
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, nitric-oxide synthase (flavodoxin).
EC created 1992, modified 2012, modified 2017
ec00220  Arginine biosynthesis
ec00330  Arginine and proline metabolism
ec00460  Cyanoamino acid metabolism
ec01100  Metabolic pathways
ec01110  Biosynthesis of secondary metabolites
ec01130  Biosynthesis of antibiotics
K13240  nitric-oxide synthase, brain
K13241  nitric-oxide synthase, inducible
K13242  nitric-oxide synthase, endothelial
K13427  nitric-oxide synthase, plant
HSA: 4842(NOS1) 4843(NOS2) 4846(NOS3)
PTR: 455026(NOS2) 463893(NOS3) 467139(NOS1)
PPS: 100974638(NOS3) 100976546(NOS2) 100996089(NOS1)
GGO: 101128007(NOS3) 101134923(NOS2) 101147071(NOS1)
PON: 100433069(NOS1) 100436584(NOS2) 100447953(NOS3)
NLE: 100589003(NOS2) 100592456(NOS3) 100597250(NOS1) 100598590
MCC: 693781(NOS1) 706921(NOS2) 714231(NOS3)
MCF: 102121432(NOS2) 102123521(NOS1) 102143504(NOS3)
CSAB: 103227233(NOS3) 103242598 103242600(NOS2)
RRO: 104666105 104669357(NOS2) 104675393(NOS3) 104675533(NOS1)
RBB: 108532525(NOS3) 108539288(NOS1) 108539916 108539959(NOS2)
CJC: 100403192(NOS2) 100405019(NOS3) 100895717(NOS1)
SBQ: 101034220(NOS3) 101034544(NOS1) 101041016(NOS2)
MMU: 18125(Nos1) 18126(Nos2) 18127(Nos3)
RNO: 24598(Nos1) 24599(Nos2) 24600(Nos3) 497963
CGE: 100758127(Nos1) 100760062(Nos2) 100769961(Nos3)
NGI: 103724501(Nos2) 103745303(Nos3) 103745523(Nos1)
HGL: 101699617(Nos2) 101711110(Nos3) 101711993(Nos1)
CCAN: 109686387(Nos1) 109693015(Nos2) 109694442(Nos3)
OCU: 100008833(NOS2) 100009243(NOS1) 100009498(NOS3)
TUP: 102471872(NOS2) 102480558(NOS1) 102495986(NOS3)
CFA: 403784(NOS3) 403822(NOS2) 477498(NOS1)
AML: 100468087(NOS1) 100470060(NOS2) 100483990(NOS3)
UMR: 103660958(NOS3) 103661304(NOS1) 103667420(NOS2)
ORO: 101375441(NOS1) 101380967(NOS2) 101382350(NOS3)
FCA: 101087020(NOS2) 101096463(NOS3) 101100342(NOS1)
PTG: 102950049(NOS2) 102962715(NOS1) 102967516(NOS3)
AJU: 106969560(NOS3) 106971710(NOS1) 106984382(NOS2)
BTA: 282876(NOS2) 287024(NOS3) 536132(NOS1)
BOM: 102265893(NOS2) 102267556(NOS3) 102280537(NOS1)
BIU: 109557793(NOS3) 109571319(NOS1) 109574459(NOS2)
PHD: 102317388(NOS1) 102325091(NOS2) 102327398(NOS3)
CHX: 100860742(NOS2) 102185338(NOS3) 102185490(NOS1)
OAS: 443073(NOS3) 443077(NOS3) 443078(NOS2) 443533(NOS1)
SSC: 100520934(NOS1) 396859(NOS2) 397557(NOS3)
CFR: 102508946(NOS1) 102518523(NOS2) 102524296(NOS3)
CDK: 105088198(NOS2) 105104911(NOS1) 105105831(NOS3) 105106782
BACU: 103003780(NOS2) 103008209(NOS1) 103017861(NOS3)
LVE: 103074308(NOS2) 103087259(NOS3) 103090138(NOS1)
OOR: 101273057(NOS1) 101280520(NOS3) 101280638(NOS2)
ECB: 100051079(NOS1) 100063339(NOS3) 791246(NOS2)
EAI: 106823361(NOS3) 106839766(NOS1) 106844596(NOS2)
MYB: 102253125(NOS2) 102256555(NOS3) 102260489(NOS1)
MYD: 102763635(NOS1) 102764374(NOS3) 102768087(NOS2)
HAI: 109382238(NOS1) 109385084(NOS2) 109389680(NOS3)
RSS: 109435172(NOS3) 109447250(NOS2) 109459480(NOS1)
PALE: 102878456(NOS2) 102879945(NOS3) 102884569(NOS1)
LAV: 100668912(NOS3) 100673992(NOS1) 100676634(NOS2)
MDO: 100013712(NOS1) 100018035(NOS3) 100024271(NOS2)
SHR: 100913437(NOS3) 100921140(NOS1) 100927789(NOS2)
OAA: 100075386(NOS2) 100079842(NOS1) 100091599(NOS3)
GGA: 107057170 395807(NOS2) 427721(NOS1)
MGP: 100538441(NOS1) 100545552(NOS3) 692136(NOS2)
CJO: 107308662(NOS3) 107321466(NOS1) 107322733(NOS2)
APLA: 101798766(NOS1) 101804455(NOS2)
ACYG: 106043795(NOS2) 106045554(NOS1)
TGU: 100230954(NOS2) 100231414(NOS1)
GFR: 102042821(NOS1) 102044468(NOS2)
FAB: 101816936 101817488(NOS2) 101820761(NOS1)
PHI: 102106809(NOS1) 102108817(NOS2) 102112141(NOS3)
PMAJ: 107211573(NOS1) 107212812(NOS2)
CCW: 104690967(NOS2) 104695038(NOS1)
FPG: 101916747(NOS1) 101918492(NOS3) 101921726(NOS2)
FCH: 102047821(NOS1) 102048023(NOS2) 102057360(NOS3)
CLV: 102084237 102086291(NOS2) 102093432(NOS1)
EGZ: 104121908(NOS2) 104129871(NOS1)
AAM: 106493898(NOS1) 106498669(NOS2) 106500475
ASN: 102375419(NOS2) 102380334(NOS1) 102381196(NOS3)
AMJ: 102561243(NOS1) 102575253(NOS3) 106737013(NOS2)
PSS: 102444149(NOS1) 102446334(NOS2)
CMY: 102941829(NOS1) 102942806 102946684(NOS2)
CPIC: 101937660(NOS1) 101941684(NOS2) 101952927(NOS3)
ACS: 100557597(nos3) 100561200(nos2) 100562233(nos1)
PVT: 110070797 110082598(NOS3) 110088446(NOS2) 110090104(NOS1)
GJA: 107112296(NOS1) 107118610(NOS3) 107119447(NOS2)
XLA: 108704634(nos3.L) 108707179(nos1.S) 108708038(nos2.L) 108708888(nos2.S) 373705(nos1.L)
XTR: 100486016(nos3) 100494698(nos2) 100497595(nos1)
DRE: 404036(nos2a) 563654(nos2b) 60658(nos1)
IPU: 108255344(nos1) 108277518(NOS2b2) 108278375(nos2)
TRU: 101066909(nos1)
LCO: 104923687(nos1)
NCC: 104967506(nos1)
MZE: 101485683(nos1)
OLA: 100049502(nos1)
XMA: 102233853(nos1)
PRET: 103469871(nos1)
NFU: 107386248(nos1)
CSEM: 103396877 103397851(nos1)
LCF: 108903114(nos1)
HCQ: 109525272(nos1)
BPEC: 110155016(nos1)
ELS: 105013989(nos2) 105031277(nos1) 109615805
SFM: 108927312(nos1) 108932266(nos2)
LCM: 102348281(NOS1) 102354990(NOS2)
CMK: 103183299(nos2) 103184386(nos1)
CIN: 100183039
DME: Dmel_CG6713(Nos)
DSI: Dsimw501_GD22223(Dsim_GD22223)
AAG: 5572370
AME: 503861(NOS)
BIM: 100749227
BTER: 100650517
SOC: 105200228
AEC: 105149468
PBAR: 105432905
HST: 105183230
CFO: 105250272
LHU: 105675559
PGC: 109856190
NVI: 100313941(Nos)
TCA: 655549
DPA: 109546644
NVL: 108558954
BMOR: 100144542(NOS2) 692510(NOS1)
API: 100160390
DNX: 107172687
ZNE: 110828058
FCD: 110850636
TUT: 107370056
CRG: 105322950
MYI: 110460719
OBI: 106875654
HMG: 101240122
ATH: AT3G47450(NOA1)
CRB: 17885274
BRP: 103873244
BOE: 106336370
THJ: 104819450
CPAP: 110823388
CIT: 102609531
TCC: 18605348
GRA: 105764892
DZI: 111291243
EGR: 104449744
VRA: 106779222
VAR: 108338876
CCAJ: 109799300
CAM: 101502582
LJA: Lj3g3v3640230.1(Lj3g3v3640230.1) Lj3g3v3640230.2(Lj3g3v3640230.2)
ADU: 107477402
AIP: 107629644
LANG: 109346733
PPER: 18787454
PMUM: 103333445
PAVI: 110764709
MDM: 103439617
CSV: 101215455
CMO: 103504692
MCHA: 111026165
CMAX: 111468852
CMOS: 111435614
CPEP: 111808842
RCU: 8289609
JCU: 105648618
POP: 18094012
VVI: 100265605
SLY: 778272(NOS1)
SPEN: 107014849
SOT: 102577659
CANN: 107863453
NTA: 107785662 107819728(NOS1)
NSY: 104222140
NTO: 104094540
INI: 109151404
SIND: 105160612
OEU: 111390921
HAN: 110915439
LSV: 111901618
DCR: 108219256
BVG: 104906620
SOE: 110782360
NNU: 104602366
OSA: 4328006
DOSA: Os02t0104700-01(Os02g0104700)
OBR: 102721991
BDI: 100824396
ATS: 109734442(LOC109734442)
SBI: 8066480
ZMA: 100381773
SITA: 101766392
PDA: 103710739
MUS: 103973495
DCT: 110108324
AOF: 109822646
ATR: 18428833
PPP: 112284854
APRO: F751_5878
 » show all
1  [PMID:1689048]
Bredt DS, Snyder SH.
Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme.
Proc Natl Acad Sci U S A 87:682-5 (1990)
2  [PMID:1706713]
Stuehr DJ, Kwon NS, Nathan CF, Griffith OW, Feldman PL, Wiseman J
N omega-hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine.
J Biol Chem 266:6259-63 (1991)
3  [PMID:11279231]
Stuehr D, Pou S, Rosen GM
Oxygen reduction by nitric-oxide synthases.
J Biol Chem 276:14533-6 (2001)
4  [PMID:19805284]
Agapie T, Suseno S, Woodward JJ, Stoll S, Britt RD, Marletta MA
NO formation by a catalytically self-sufficient bacterial nitric oxide synthase from Sorangium cellulosum.
Proc Natl Acad Sci U S A 106:16221-6 (2009)
5  [PMID:21119059]
Foresi N, Correa-Aragunde N, Parisi G, Calo G, Salerno G, Lamattina L
Characterization of a nitric oxide synthase from the plant kingdom: NO generation from the green alga Ostreococcus tauri is light irradiance and growth phase dependent.
Plant Cell 22:3816-30 (2010)
Other DBs
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IUBMB Enzyme Nomenclature:
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BRENDA, the Enzyme Database:
CAS: 125978-95-2

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