Module 2: Figure NO synthase mechanism
Nitric oxide synthase (NOS) reaction mechanism.
The two nitric oxide synthase (NOS) monomers are lined up alongside each other so that the reductase domain of one functions together with the oxidase domain of its neighbour. The enzyme dimer also functions as a scaffold to organize the other components of the reaction mechanism such as the bound cofactors [flavin–adenine dinucleotide (FAD), flavin adenine mononucleotide (FMN), haem and tetrahydrobiopterin (BH4)] and the tightly bound prosthetic group calmodulin (CaM). The formation of NO is driven by an NADPH-dependent electron flux that passes from the reductase towards the oxidase domain. The attached haem is the terminal electron acceptor, which binds the oxygen that is inserted into arginine to form the hydroxyarginine that decays to release NO. One of the important regulators of NOS is calmodulin, which is constitutively active in inducible NOS (iNOS), but requires an elevation of Ca2+ for both neuronal NOS (nNOS) and endothelial NOS (eNOS). One consequence of increasing the concentration of Ca2+ in cells is therefore to increase the formation of NO.