Sandbox 5
Introduction to NOSIntroduction to NOS
Nitric Oxide Synthase (NOS) is a group of enzymes catalysing L-arginine to yield L-Citrulline and Nitric Oxide[1] (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.
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 the amino acid Cystein present in the oxygenase. Binding of the 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 is a Flavin mononucleotide. FMN passes the electron on to the Heme in the oxygenase domain on the opposite subunit. The oxygenase domain contains BH4 (5,6,7,8-tetrahydrobiopterin)and the already mentioned Heme ion (Fe(III)). These two are also redox active groups. BH4 is required by NOS in order to produce NO and not H2O2. Besides Heme and BH4, the oxygenase domain binds the substrate L-arginine which takes part in the NO synthase reaction (see below).
In mammals three isozymes of NOS has been identified: Neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). (~The NOS enzymes is found in numeral organisms. Most facts used here is 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.
The NOS reaction requires five redox-active cofactors.