[Mechanisms of nitric oxide synthesis and action in cells]

Nitric oxide (NO) is a free radical gas, which is a product of reaction between molecular oxygen and L-arginine. Great diffusibility of nitric oxide determines its quick three-dimensional distribution around the cell which is a source of nitric oxide. Single electron makes it into very reactive radical, interacting with metals incorporated in enzyme structure, heme, superoxids, oxygen, etc. The synthesis of nitric oxide is catalyzed by enzyme nitric oxide synthase (NOS) which has three isoforms: endothelial nitric oxide synthase, neuronal nitric oxide synthase, macrophagal nitric oxide synthase. Due to mechanisms of action NOS enzymes are also classified as constitutive nitric oxide synthase and inducible nitric oxide synthase. Constitutive forms are found in cytosol and membranes, they are dependent on Ca(2+)/calmodulin concentration and are extremely important in the regulation of physiological processes. Inducible forms are synthesized in cells after induction by bacterial endotoxins or cytokines, do not depend on Ca(2+)/calmodulin concentration and are being considered as pathological isoforms. It is thought that nitric oxide synthase catalyses transport of electrons for reactions between molecular oxygen and L-arginine. This consideration based on fact that flavine co-enzymes and hem are found as structural units in nitric oxide synthase. Although all isoforms catalyze the same reactions, every one of them has its own unique structure and localization. These features determine differences of activation pathways as well as specificity of inhibitors. The characteristic features of nitric oxide and functional differences among the nitric oxide synthase isoforms determine its different role in regulation of many physiological and pathophysiological processes.