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Nitric oxide synthase information


Nitric-oxide synthase
Human inducible nitric oxide synthase. PDB 1nsi
Identifiers
EC no.1.14.13.39
CAS no.125978-95-2
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
Nitric oxide synthase, oxygenase domain
Structure of endothelial nitric oxide synthase heme domain.[1]
Identifiers
SymbolNO_synthase
PfamPF02898
InterProIPR004030
SCOP21nos / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Nitric oxide synthases (EC 1.14.13.39) (NOSs) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule. It helps modulate vascular tone, insulin secretion, airway tone, and peristalsis, and is involved in angiogenesis and neural development. It may function as a retrograde neurotransmitter. Nitric oxide is mediated in mammals by the calcium-calmodulin controlled isoenzymes eNOS (endothelial NOS) and nNOS (neuronal NOS).[2] The inducible isoform, iNOS, involved in immune response, binds calmodulin at physiologically relevant concentrations, and produces NO as an immune defense mechanism, as NO is a free radical with an unpaired electron. It is the proximate cause of septic shock and may function in autoimmune disease.

NOS catalyzes the reaction:[3]

  • 2 L-arginine + 3 NADPH + 3 H+ + 4 O2 2 citrulline +2 nitric oxide + 4 H2O + 3 NADP+

NOS isoforms catalyze other leak and side reactions, such as superoxide production at the expense of NADPH. As such, this stoichiometry is not generally observed, and reflects the three electrons supplied per NO by NADPH.

Eukaryotic NOS isozymes are catalytically self-sufficient. The electron flow is: NADPH → FAD → FMN → heme → O2. Tetrahydrobiopterin provides an additional electron during the catalytic cycle which is replaced during turnover. Zinc, though not a cofactor, also participates but as a structural element.[4] NOSs are unique in that they use five cofactors and are the only known enzyme that binds flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), heme, tetrahydrobiopterin (BH4) and calmodulin.[citation needed]

  1. ^ PDB: 3N5P​; Delker SL, Xue F, Li H, Jamal J, Silverman RB, Poulos TL (December 2010). "Role of zinc in isoform-selective inhibitor binding to neuronal nitric oxide synthase". Biochemistry. 49 (51): 10803–10. doi:10.1021/bi1013479. PMC 3193998. PMID 21138269.
  2. ^ Ahmad, Nashrah; Ansari, Mohammad Y.; Haqqi, Tariq M. (October 2020). "Role of iNOS in osteoarthritis: Pathological and therapeutic aspects". Journal of Cellular Physiology. 235 (10): 6366–6376. doi:10.1002/jcp.29607. ISSN 0021-9541. PMC 8404685. PMID 32017079.
  3. ^ Cite error: The named reference pmid7510950 was invoked but never defined (see the help page).
  4. ^ Cortese-Krott M, Kulakov L, Opländer C, Kolb-Bachofen V, Kröncke K, Suschek C (July 2014). "Zinc regulates iNOS-derived nitric oxide formation in endothelial cells". Redox Bio. J. 2014 (2): 945–954. doi:10.1016/j.redox.2014.06.011. PMC 4143817. PMID 25180171.

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American pharmacologist. For demonstrating the signaling properties of nitric oxide, he was co-recipient of the 1998 Nobel Prize in Physiology or Medicine...

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of nitric oxide from the amino acid arginine, catalyzed by nitric oxide synthase. Citrulline can be derived from: from arginine via nitric oxide synthase...

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role remains unclear. In humans, nitric oxide is produced from L-arginine by three enzymes called nitric oxide synthases (NOS): inducible (iNOS), endothelial...

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cells. NO is biosynthesized endogenously from L-arginine by various nitric oxide synthase (NOS) enzymes. Reduction of inorganic nitrate may also serve to...

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(including metabolism of some drugs), gas sensing (guanyl cyclases, nitric oxide synthase), and microRNA processing (DGCR8). Heme is a coordination complex...

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molecules derived from nitric oxide (•NO) and superoxide (O2•−) produced via the enzymatic activity of inducible nitric oxide synthase 2 (NOS2) and NADPH...

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N-methyl-D-aspartate receptor (NMDA receptor), which has been associated with nitric oxide synthase (NOS) and cGMP/PKG pathway activation and a decrease of Na+,K+-ATPase...

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imidazoles, including clotrimazole, are selective inhibitors of nitric oxide synthase, which makes them interesting drug targets in inflammation, neurodegenerative...

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inhibitor of nitric oxide synthase and hence a vasoconstrictor. As such, it finds widespread use as a biochemical tool in the study of nitric oxide and its...

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Palmar erythema

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H, Fandino J, Fathi AR (2015). "Estrogen Induces Nitric Oxide Production Via Nitric Oxide Synthase Activation in Endothelial Cells". Neurovascular Events...

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production of inducible nitric oxide synthase (NOS). This allows citrulline, a byproduct of the NOS-catalyzed production of nitric oxide, to be recycled to...

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N-Methylarginine is an inhibitor of nitric oxide synthase. Chemically, it is a methyl derivative of the amino acid arginine. It is used as a biochemical...

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