Summary
The monovalent reduction of molecular oxygen, resulting in the formation of superoxide radicals (\(O_{\dot 2}^ - \)) is regarded as to be an ongoing physiological process involved in the respiration and other biological processes of aerobic cells. These reactive oxygen species have been reported to function as cofactors in many biosynthetic reaction steps. Thus, deviations from cellular steady state concentrations may lead to a multiplicity of clinical symptoms or may to a great deal determine the characteristic of a distinct malady. Decrease of cellular\(O_{\dot 2}^ - \)-concentration is discussed in connection with Trisomie 21 and various mental disorders. The role of\(O_{\dot 2}^ - \) in the biochemistry of inflammation, autoimmune diseases, various toxicological cases and the biological aging process is described. Hypothetical considerations concerning the involvement of\(O_{\dot 2}^ - \) in the pathogenetic mechanisms of Morbus Wilson, haemochromatosis, Parkinson syndrome, cataractogenesis and in carcinogenesis are presented. The physiological control of cellular\(O_{\dot 2}^ - \)-concentration is performed by formation rates of the various cellular\(O_{\dot 2}^ - \)-sources and the overall elimination rates of\(O_{\dot 2}^ - \)-consuming reaction steps. Superoxide dismutase (SOD) is of special interest within this cycle because it detoxifies\(O_{\dot 2}^ - \) radicals with velocity rates which are significantly faster than any other pathway involved in\(O_{\dot 2}^ - \) elimination. Thus, attempts for a therapeutic interference on tissue levels of\(O_{\dot 2}^ - \)-radicals are mainly based on inhibition or activation of cellular SOD-activities depending on a supposed decrease or increase in cellular steady state concentrations of\(O_{\dot 2}^ - \). The availability of a drug version of SOD and of various synthetic SOD-active compounds allows a therapeutic decrease of\(O_{\dot 2}^ - \)-tissue levels. Inhibition of cellular SOD is also possible, however, many still unknown toxic side effects should be expected because of unspecific action of the inhibitor available.
Zusammenfassung
Die univalente Reduktion des atmosphärischen Sauerstoffs, welche zur Bildung von Superoxidradikalen (\(O_{\dot 2}^ - \)) führt, ist als physiologischer Vorgang bei der Atmung und anderer biologischer Leistungen aerober Zellen anzusehen. Diese reaktiven Sauerstoffspezies sind als Cosubstrate für viele biologische Syntheseschritte nachgewiesen worden. Regulationsstörungen zellulärer\(O_{\dot 2}^ - \)-Konzentrationen können daher in vielfätiger Weise krankheitstypischen Symptomen zugeordnet werden oder weitgehend die Charakteristik einer Erkrankung prägen. Ein Absinken zellulärer\(O_{\dot 2}^ - \)-Konzentrationen wird in der vorliegenden Übersichtsarbeit im Zusammenhang mit der Trisomie 21, sowie verschiedenen psychiatrischen Erkrankungen diskutiert. Der mehr oder weniger gesicherten Bedeutung erhöhter\(O_{\dot 2}^ - \)-Konzentration bei chronisch inflammatorischen Prozessen, autoimmunologischen und verschiedenen toxikologischen Erkrankungen, sowie beim Prozeß des biologischen Alterns werden hypothetische Überlegungen zur Rolle der Superoxidradikale beim Morbus Wilson, der Hämatochromatose, dem Parkinson Syndrom, der Kataraktogenese und der Carcinogenese gegenübergestellt. Die physiologische Regulation zellulärer\(O_{\dot 2}^ - \)-Konzentration erfolgt sowohl über die Aktivitäten verschiedener zellulärer Bildungsquellen als auch über die Elimination durch\(O_{\dot 2}^ - \)-verbrauchende Reaktionsschritte. Eine besondere regulatorische Rolle fällt dabei dem Enzym Superoxiddismutase (SOD) zu, da es von allen in Frage kommenden Rekationen\(O_{\dot 2}^ - \)-Radikale mit der größten Geschwindigkeitskonstanten umsetzt, während umgekehrt eine Erhöhung der\(O_{\dot 2}^ - \)-Konzentration im allgemeinen eher auf einer Bildungsstimulierung beruht. Der Versuch der therapeutischen Beeinflussung zielt daher sowohl auf eine Hemmung als auch auf eine Erhöhung der zellulären SOD-Aktivitäten, je nachdem, ob ein Absinken oder Ansteigen zellulärer\(O_{\dot 2}^ - \)-Konzentrationen vermutet wird. Letzteres ist durch die Gabe des isolierten Enzyms oder anderer SOD-aktiver Verbindungen möglich und in der klinischen Erprobung. Eine Hemmung der körpereigenen SOD ist ebenfalls möglich, dürfte jedoch wegen der unspezifischen Wirkung therapeutisch zur Zeit nicht anwendbar sein.
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Nohl, H. Physiologische und pathophysiologische Bedeutung von Superoxid-Radikalen und die regulatorische Rolle des Enzyms Superoxiddismutase. Klin Wochenschr 59, 1081–1091 (1981). https://doi.org/10.1007/BF01746195
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DOI: https://doi.org/10.1007/BF01746195