Классификация. INOS and nNOS are soluble and found predominantly

INOS and nNOS are soluble and found predominantly in the cytosol, while eNOS is membrane associated.

NO produced by eNOS has been shown to be a vasodilator identical to the endothelium-derived relaxing factor. NO activates guanylate cyclase, which induces smooth muscle relaxation by:

• Increased intracellular cGMP, which inhibits calcium entry into the cell, and decreases intracellular calcium concentrations
• Activation of K⁺ channels, which leads to hyperpolarization and relaxation
• Stimulates a cGMP-dependent protein kinase that activates myosin light chain phosphatase, the enzyme that dephosphorylates myosin light chains, which leads to smooth muscle relaxation.

The neuronal isoform nNOS is involved in the development of nervous system. It functions as a retrograde neurotransmitter important in long term potentiation and hence is likely to be important in memory and learning. nNOS has many other physiological functions, including regulation of cardiac function and peristalsis and sexual arousal in males and females.

The inducible isoform iNOS produces large amounts of NO as a defense mechanism. It is synthesized by many cell types in response to cytokines and is an important factor in the response of the body to attack by parasites, bacterial infection, and tumor growth. It is also the cause of septic shock and may play a role in many diseases with an autoimmune etiology.

The enzymes exist as homodimers. In eukaryotes, each monomer consisting of two major regions: an N-terminal oxygenase domain, which belongs to the class of heme-thiolate proteins, and a multi-domain C-terminal reductase, which is homologous to NADPH:cytochrome P450 reductase and other flavoproteins. The interdomain linker between the oxygenase and reductase domains contains a calmodulin-binding sequence.

Nitric oxide may itself regulate NOS expression and activity. Specifically, NO has been shown to play an important negative feedback regulatory role on NOS3, and therefore vascular endothelial cell function. This process, known formally as S -nitrosylation, has been shown to reversibly inhibit NOS3 activity in vascular endothelial cells.