Peroxynitrite

Peroxinitrite ( ONOO - ) belong to the reactive nitrogen and oxygen species ( RNOS; engl reactive nitrogen oxide species or ROS, . Engl reactive oxygen species. ). In an organism, these compounds can with other compounds ( proteins, DNA) react and cause damage.

Peroxinitrite arising from nitric oxide and superoxide radicals.

Superoxide and nitric oxide ( • NO) occur in the metabolism continuously in many different processes, such as formation of NO from nitrite, the NO synthase ( NOS), as part of the immune system, in the auto-oxidation of biological molecules or reactions of xanthine oxidase (XO ).

Neither superoxide nor NO are toxic in vivo, as long as both do not occur together in non-physiologically high concentrations or. Superoxide radicals are mitigated by means of superoxide dismutases (SOD ) and peroxidases rapidly (O2 • - → H2O2 → O2, H2O). NO, however, predominantly reacts with oxygenated hemoglobin to form nitrates.

Because of these and still other protective mechanisms (eg, glutathione, ascorbic acid, tocopherol) is the emergence of yet more toxic substances are prevented. If this absence can Peroxinitrite and hydroxyl radicals ( • OH ) are produced.

Hydroxyl radicals react very rapidly due to their high reactivity with the nearest connection. Peroxinitrite other hand, have a longer half-life and can react with the more selective compounds. They are used for example by macrophages to ward off germs. They are highly potent cytotoxins and are formed by diffusion-controlled reaction between NO and superoxide radicals (O2 • - • NO → ONOO - ). The result is thus rapidly when NO and superoxide simultaneously occur in larger amounts or can not be sufficiently reduced. Thus, the formation of peroxynitrite rise to the Einmillionenfache under strongly pro-inflammatory conditions. Since superoxide radicals diffuse significantly worse in comparison with the NO radical and have a short half-life, the Peroxinitritentstehung is primarily associated with the formation of superoxide radicals. Peroxynitrite itself can exert its damaging effect within one to two cell diameters with a ( physiological ) half-life of approximately 10 ms.

Peroxynitrite and the resulting radicals can damage enzymes, the genetic material (DNA) that cause the mitochondria and membranes; Signaling cascades can be altered or disturbed; the formation of Lewy bodies is favored and, ultimately, apoptosis can be initiated or caused necrosis. Vascular and cardiovascular disease, circulation shock, immune system disorders, pain, neurodegeneration, aging and others are associated with the Peroxinitritentstehung.

Thus, peroxynitrite reacts with carbon dioxide to always present the short-lived Nitrosoperoxycarbonat ion, which is divided into two highly reactive radicals that are responsible for DNA damage by peroxynitrite:

Most of the numerous endo - and exogenous peroxynitrite " scavenger" or - " neutralizer " interact only with the secondary resulting radicals ( for example, with • OH · NO2, CO3 • -) and so have only a limited or low efficacy. Metalloporphyrins, however ( for example, oxygenated hemoglobin ) react directly and rapidly with peroxynitrite. Fe ( III) porphyrins inactivate peroxynitrite by isomerize it to nitrate. Corresponding compounds are being developed for clinical use and seem to offer promising treatment options mentioned diseases.