An important messenger molecule in mammals and other animals. It can be toxic or beneficial, depending on the amount and where in the body it is released. Initial research into the chemistry of nitric oxide (NO) was motivated by its production in car engines, which results in photochemical smog and acid rain. In the late 1980s, researchers in immunology, cardiovascular pharmacology, neurobiology, and toxicology discovered that nitric oxide is a crucial physiological messenger molecule. Nitric oxide is now thought to play a role in blood pressure regulation, control of blood clotting, immune defense, digestion, the senses of sight and smell, and possibly learning and memory. Nitric oxide may also participate in disease processes such as diabetes, stroke, hypertension, impotence, septic shock, and long-term depression. See Immunology, Neurobiology
Most cellular messengers are large, unreactive biomolecules that make specific contacts with their targets. In contrast, nitric oxide is a small molecule that contains a free radical—that is, an unpaired electron—making it very reactive. Nitric oxide can freely diffuse through aqueous solutions or membranes, reacting rapidly with metal centers in cellular proteins and with reactive groups in other cellular molecules.
Nitric oxide is produced in the body by an enzyme called nitric oxide synthase, which converts the amino acid l -arginine to nitric oxide and l -citrulline. There are three types of nitric oxide synthase: brain, endothelial, and inducible. Both brain and endothelial enzymes are constitutive, that is, they are always present in cells, while the production of inducible nitric oxide synthase can be turned on or off when a system needs nitric oxide. After nitric oxide is produced in specific areas of the body by nitric oxide synthase, it diffuses to nearby cells. Nitric oxide then reacts preferentially in the interior of these cells with the metal centers of proteins. Nitric oxide binds specifically to the iron (Fe) atom of the heme group in proteins; it can also interact with other metal sites in proteins as well as with the thiol group (SH) of the amino acid cysteine. The interaction of nitric oxide with these proteins causes a cascade of intracellular events that leads to specific physiological changes within cells. For example, nitric oxide causes the smooth muscle cells surrounding blood vessels to relax, decreasing blood pressure. Nitric oxide plays an important role in the central and peripheral nervous systems; the overproduction of nitric oxide in brain tissues has been implicated in stroke and other neurological problems.
Nitric oxide also functions as an important agent in the immune system by killing invading bacterial cells. Nitric oxide released by macrophages can inhibit important cellular processes in the bacteria, including deoxyribonucleic acid (DNA) synthesis and respiration, by binding to and destroying iron-sulfur centers in key enzymes in these pathways.
Although nitric oxide production in the immune system serves a crucial biological function, there can be adverse effects when too much nitric oxide is produced. During a massive bacterial infection, excess nitric oxide can go into the vascular system, causing a dramatic decrease in blood pressure, which may lead to possibly fatal septic shock. Thus, scientists are working on drugs that can selectively inhibit the inducible form of nitric oxide synthase in order to avoid the harmful effects produced by excess nitric oxide without interfering with useful nitric oxide pathways.