Nitric Oxide Synthase: Difference between revisions

In mammals three isozymes of NOS have been identified: Neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS)<ref>Flemming, I., Chapter 3, Biology of Nitric Oxide Synthases, from Microcirculation, Editors Ronald F. Tuma, R. F., Durán, W. N., and Ley, K., 2nd edition, Academic Press, 2008</ref>. (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. Endothelial NOS is controlling the amount of NO signaling in the endothelial cells eg. blood vessel dilation.  An overview of 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.  

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Each NOS monomer is composed of two domains: an N-terminal oxygenase domain and a C-terminal reductase domain. Each subunit is held together by a zinc ion, which is bound by two cysteines from each oxygenase domain. Calmodulin binds to a linker region between the two domains and is necessary for activity. 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 5,6,7,8-tetrahydrobiopterin (H₄B) and the already mentioned heme. These two are also redox active groups. Besides Heme and H₄B, the oxygenase domain binds the substrate L-arginine which takes part in the NO synthase reaction (see below).