The basics about nitric oxide

Nitric oxide is a gas and a free radical which is now recognised to have very important physiological roles. It is synthesised enzymatically from the amino acid L-arginine in a number of tissues using the three isoforms of nitric oxide synthase, one of which is inducible and can form much large amounts of NO. NO is important in the endothelium-dependent regulation of blood flow and pressure as well as inhibiting the activation of blood platelets. NO is recognised as a neurotransmitter at least in certain types of nerves. Along with other free radicals, NO is also important in the primary defence mechanisms against attack by micro-organisms. NO has a close interaction with iron-containing proteins and binds to haem. By this process NO activates a haem-containing enzyme called soluble guanylyl cyclase which is activated a thousand fold to produce the signalling molecule cyclic GMP. This has many effects at the molecular level to set in train the pathways which propagate the diverse physiological actions of NO. Although this pathway through cyclic GMP is important, this is by no means the only mechanism by which NO influences the activities of the cell. These alternative pathways depend on modification of the structure of enzymes and structural proteins in several different ways. Most of these modifications result from the actions of NO with other free radicals such as oxygen and superoxide anions to produce reactive oxidants. The oxidants modify the proteins by, among others, nitrosation and nitration of proteins of thiol groups and aromatic amino acids respectively. These changes introduce potential new subtleties to the effects on NO on cellular function which are only now being explored. Protein modifications by NO are even more evident in many inflammatory disorders and may account, at least to some extent, to the pathology seen in these conditions.