| Nitric-oxide synthase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Human inducible nitric oxide synthase. PDB 1nsi | |||||||||
| Identifiers | |||||||||
| EC no. | 1.14.13.39 | ||||||||
| CAS no. | 125978-95-2 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
| Nitric oxide synthase, oxygenase domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Structure of endothelial nitric oxide synthase heme domain.[1] | |||||||||
| Identifiers | |||||||||
| Symbol | NO_synthase | ||||||||
| Pfam | PF02898 | ||||||||
| InterPro | IPR004030 | ||||||||
| SCOP2 | 1nos / SCOPe / SUPFAM | ||||||||
| |||||||||
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]
- ^ 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.
- ^ 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.
- ^ Cite error: The named reference
pmid7510950was invoked but never defined (see the help page). - ^ 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.