Nitric oxide (NO) has a broad range of biological activities and is implicated in signaling pathways in phylogenetically diverse species. Nitric oxide synthases (NOS), the enzymes responsible for synthesis of NO, are homodimers whose monomers are themselves two fused enzymes: a cytochrome reductase and a cytochrome that requires three cosubstrates (L-arginine, NADPH, and oxygen) and five cofactors or prosthetic groups (FAD, FMN, calmodulin, tetrahydrobiopterin, and heme). Several distinct NOS isoforms are produced from three distinct genes. These include two constitutive Ca2+/CaM-dependent forms of NOS: nNOS (also designated bNOS, NOS-I), whose activity was first identified in neurons and eNOS (also designated ecNOS, NOS-III) first identified in endothelial cells. The inducible form of NOS, iNOS (also designated NOS-II), is Ca2+ independent and is expressed in a broad range of cell types. This form of NOS is induced after stimulation with cytokines and exposure to microbial products.
