Nitric Oxide Synthase: Difference between revisions

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== Introduction to NOS ==
== Introduction to Nitric Oxide Synthase ==


Nitric Oxide Synthase (NOS) is a group of enzymes catalysing L-arginine to yield L-Citrulline and Nitric Oxide[http://en.wikipedia.org/wiki/Nitric_Oxide] (NO). NOS is a homodimeric protein with 125- to 160-kD subunits. An overview of the NOS homodimer is given below. All cofactors are included and the electron transfer pathway which takes place in NOS is indicated.  
Nitric Oxide Synthase (NOS) is an enzyme catalysing the formation of L-Citrulline and Nitric Oxide[http://en.wikipedia.org/wiki/Nitric_Oxide] (NO) from L-arginine. NOS is a homodimeric protein with 125- to 160-kD subunits.  


[[Image:NOS_OVERSIGT.JPG|800 px|right]]
In mammals three isozymes of NOS has been identified: Neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). (~The NOS enzymes are found in numeral organisms. Most facts used here are from the human NOS, but sites from different organisms are used.~). Neuronal NOS is producing NO in the nervous tissue in both the peripheral and the central nervous system. nNOS is functioning in cell signaling and communication - a vital part of the nervous tissue. Inducible NOS is connected with the immune system or in general...(!?). Endothelial NOS is controlling the amount of NO signaling in the endothelial cells eg. blood vessel dilation.  An overview the structural organization of the NOS homodimer is given below. All cofactors are included and the electron transfer pathway which takes place in NOS is indicated.  


The NOS homodimer is composed of two subunits, each containing two domains: an oxygenase domain and a reductase domain. The subunits are held together by a Zinc ion, which is bound by 4 cystein amino acids present in the oxygenase domain, two in each domain. Further, many amino acid interactions also hold the sunbunits together. Binding of the two types of domains is caused by CaM. The reductase domain supplies electrons for the NOS reaction which takes place in the oxygenase domain. The reductase domain contains two redox-active prosthetic groups, FAD and FMN. NADPH binds to the domain and passes on an electron to FAD which passes the electron on to FMN. FMN passes the electron on to the Heme in the oxygenase domain of the opposite subunit. The oxygenase domain contains H<sub>4</sub>B (5,6,7,8-tetrahydrobiopterin)and the already mentioned Heme ion (Fe(III)). These two are also redox active groups. H<sub>4</sub>B is required by NOS in order to produce NO and not H<sub>2</sub>O<sub>2</sub>. Besides Heme and H<sub>4</sub>B, the oxygenase domain binds the substrate L-arginine which takes part in the NO synthase reaction (see below).
[[Image:NOS_OVERSIGT.JPG|400 px|right]]


In mammals three isozymes of NOS has been identified: Neuronal NOS [[(nNOS)]], inducible NOS [[(iNOS)]], and endothelial NOS [[(eNOS)]]. One differentiates between constitutive NOS (always produced - eNOS and nNOS) and inducable NOS (iNOS). Constitutive NOS are regulated by calcium binding to the CaM region and is thus regulated by calcium. nNOS produces NO in nervous tissue in both the peripheral and the central nervous system. nNOS functions in cell signaling and communication - a vital part of the nervous tissue.  eNOS controls the amount of NO signaling in the endothelial cells (eg. blood vessel dilation). iNOS is induced to produce NO only when needed. For example when the immune system is activated. iNos is not regulated by calcium. The NOS enzymes is found in numeral organisms. Most facts used at this page are taken from the human NOS. The active site and different binding regions are highly conserved and therefore sites from other organisms will be used as well.
The NOS homodimer is composed of two types of domains: an oxygenase domain and a reductase domain. Each subunit is held together by a Zinc ion, which is bound by two cysteines from each  oxygenase domain. Binding of the domains is caused by calmodulin (CaM). The reductase domain supplies electrons for the NOS reaction which takes place in the oxygenase domain. The reductase domain contains two redox-active prosthetic groups, flavin adenine dinucleotide (FAD) and Flavin mononucleotide (FMN). Nicotinamide adenine dinucleotide phosphate(NADPH) binds to the domain and passes on an electron to FAD which passes the electron on to FMN. FMN passes the electron on to the Heme in the oxygenase domain on the opposite subunit. The oxygenase domain contains H<sub>4</sub>B (5,6,7,8-tetrahydrobiopterin)and the already mentioned Heme ion (Fe(III)). These two are also redox active groups. H<sub>4</sub>B is required by NOS in order to produce NO and not H<sub>2</sub>O<sub>2</sub>. Besides Heme and H<sub>4</sub>B, the oxygenase domain binds the substrate L-arginine which takes part in the NO synthase reaction (see below).  
 
 
 
The NOS reaction requires five redox-active cofactors. ???


== The reaction of NOS ==
== The reaction of NOS ==
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