Nitric oxide synthase

Nitric oxide synthases (NOSs) are a family of <a href="/facts/Enzymes/DSI1Fh7y">enzymes</a> catalyzing the production of <a href="/facts/Nitric_oxide/UvhdvDzp">nitric oxide</a> (NO) from <a href="/facts/L-arginine/y49Hdf1e">L-arginine</a>. NO is an important <a href="/facts/Biological_functions_of_nitric_oxide/5uJGutFQ">cellular signaling</a> molecule. It helps modulate <a href="/facts/Vascular_tone/XPH12Hub">vascular tone</a>, <a href="/facts/Insulin/oXG0myt1">insulin</a> secretion, airway tone, and <a href="/facts/Peristalsis/R6zzQb1d">peristalsis</a>, and is involved in <a href="/facts/Angiogenesis/h0HF9IUd">angiogenesis</a> and neural development. It may function as a retrograde <a href="/facts/Neurotransmitter/LlpYFSU3">neurotransmitter</a>. Nitric oxide is mediated in mammals by the <a href="/facts/Calcium_in_biology/wgUxKej5">calcium</a>-<a href="/facts/Calmodulin/CbEnEYHE">calmodulin</a> controlled <a href="/facts/Isozyme/WE3tbEhf">isoenzymes</a> eNOS (<a href="/facts/Endothelial_NOS/jxYpbqWD">endothelial NOS</a>) and nNOS (neuronal NOS). The inducible isoform, iNOS, involved in immune response, binds <a href="/facts/Calmodulin/CbEnEYHE">calmodulin</a> 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 <a href="/facts/Proximate_and_ultimate_causation/gMJzgPUg">proximate cause</a> of <a href="/facts/Septic_shock/yc9mgmrz">septic shock</a> and may function in <a href="/facts/Autoimmunity/5cASmcfI">autoimmune</a> disease.
In the context of <a href="/facts/Eukaryote/SkwyPLMA">eukaryote</a> biology, nitric oxide synthase refers to nitric-oxide synthase (NADPH) (<a href="/facts/Enzyme_Commission_number/Y5GNLRKX">EC</a> <a href="https://enzyme.expasy.org/EC/1.14.13.39">1.14.13.39</a>), which catalyzes the reaction:

<ul><li>2 L-<a href="/facts/Arginine/y49Hdf1e">arginine</a> + 3 <a href="/facts/Nicotinamide_adenine_dinucleotide_phosphate/BHdLW925">NADPH</a> + 3 H+ + 4 O2 
 
 
 
 ⇌
 
 
 {\displaystyle \rightleftharpoons }
 
 2 <a href="/facts/Citrulline/1X1LFYFG">citrulline</a> +2 <a href="/facts/Nitric_oxide/UvhdvDzp">nitric oxide</a> + 4 H2O + 3 NADP+</li></ul>
NOS isoforms catalyze other leak and side reactions, such as <a href="/facts/Superoxide/2X2sQocn">superoxide</a> 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: <a href="/facts/NADPH/XMgmPQ5t">NADPH</a> → <a href="/facts/Flavin_adenine_dinucleotide/uzADx3ES">FAD</a> → <a href="/facts/Flavin_mononucleotide/cWutCJmR">FMN</a> → <a href="/facts/Heme/fRhyJAAb">heme</a> → <a href="/facts/Dioxygen/UVNYnKUQ">O2</a>. <a href="/facts/Tetrahydrobiopterin/BYrDKeLl">Tetrahydrobiopterin</a> provides an additional electron during the catalytic cycle which is replaced during turnover. <a href="/facts/Zinc/80b1qgk3">Zinc</a>, though not a cofactor, also participates but as a structural element. NOSs are unique in that they use five <a href="/facts/Cofactor_(biochemistry)/AGo0PCUU">cofactors</a> and are the only known <a href="/facts/Enzyme/DSI1Fh7y">enzyme</a> that binds <a href="/facts/Flavin_adenine_dinucleotide/uzADx3ES">flavin adenine dinucleotide</a> (FAD), <a href="/facts/Flavin_mononucleotide/cWutCJmR">flavin mononucleotide</a> (FMN), <a href="/facts/Heme/fRhyJAAb">heme</a>, <a href="/facts/Tetrahydrobiopterin/BYrDKeLl">tetrahydrobiopterin</a> (BH4) and <a href="/facts/Calmodulin/CbEnEYHE">calmodulin</a>.
The EC number 1.14.13.39 specifically refers to synthases with linked oxygenase and reductase domains, i.e. "catalytically self-sufficient" NO synthases. This kind of synthase is ound in eukaryotes and, through independent domain acquisition, <a href="/facts/Sorangium_cellulosum/7JKnn29c">Sorangium cellulosum</a>. Most bacteria and archaea have a version that only has an oxidase domain and depend on a partner protein; these are categorized as EC 1.14.14.47 "<a href="/facts/Nitric-oxide_synthase_(flavodoxin)/fufDbY3s">nitric-oxide synthase (flavodoxin)</a>". All these enzymes' oxygenase domains share a common ancestor (see "oxygenase domain" infobox).

Nitric oxide synthase open-in-new

Nitric oxide synthase