Zusammenfassung
Die mit chemischen und strahlenchemischen Methoden in vitro erarbeiteten Kenntnisse über Radikalreaktionen sind nur mit großen Einschränkungen auf die Verhältnisse in vivo übertragbar. Gesetzmäßigkeiten der chemischen Kinetik lassen sich in Strenge nur auf homogene Lösungen anwenden; zur Deutung des Geschehens in komplex zusammengesetzten und durch Kompartimentgrenzen unterteilten zellulären Strukturen ist man auf die Hilfe mehr oder weniger modellhafter Vorstellungen angewiesen, um den Verlauf einer radikalischen Reaktion zu beschreiben.
Aus den für Radikale typischen Reaktionscharakteristika lassen sich die folgenden allgemein gültigen Aussagen ableiten: Unter den in vivo herrschenden Bedingungen sind radikalische Kettenreaktionen sowohl im intra- wie auch im extrazellulären Bereich auf in Relation zu zellulären Dimensionen relativ kleine Bezirke beschränkt. Durch Reaktion mit den in der Zelle, in der Interstitialflüssigkeit oder im Blut gelösten Substanzen entstehen aus den primären Radikalen innerhalb kurzer Diffusionsstrecken andere radikalische Kettenträger und die für Radikalreaktionen charakteristischen peroxidischen Endprodukte. Erst die als Folge des primären radikalischen Prozesses entstehenden Peroxide sind relativ frei diffusibel und können mit spezifischen Targets — z.B. Bindungsstellen für Übergangsmetallionen — unter Bildung neuer Radikale reagieren. Damit läßt sich erklären, daß Radikalreaktionen, obwohl sie im Prinzip unspezifisch sind, letzten Endes doch zu ortsspezifischen Effekten fuhren können. Radikale per se sind nur unter ganz speziellen Voraussetzungen in der Lage, Kompartimentgrenzen zu überschreiten. Da aber viele ihrer peroxidischen Folgeprodukte membrangängig sind, kann es zu grenzüberschreitenden Sekundärreaktionen kommen, die in ihren chemischen Folgen von radikalischen Primärreaktionen nicht zu unterscheiden sind.
Radikalreaktionen müssen nicht notwendigerweise schädigend sein, sondern können auch — im teleologisch positiven Sinne — von der Zelle zu metabolischen und synthetischen Leistungen herangezogen werden.
Unter den Nachweismethoden eröffnen nur die aufwendigen, mehr physikalisch orientierten, Verfahren der Pulsradiolyse und der Elektronen-Spinresonanz-Spektroskopie die Möglichkeit, Radikale direkt zu identifizieren. Wegen der auftretenden schnellen Reaktionen sind chemische Nachweisverfahren mehr oder weniger darauf angewiesen, Endprodukte radikalischer Kettenreaktionen zu erfassen und daraus indirekte Schlüsse zu ziehen. Diese Schlüsse müssen durch den Einsatz spezifischer Radikalfänger überprüft und verifiziert werden. Ferner sind die Nachweismethoden zu modifizieren, je nachdem, ob intrazellulär generierte Radikale detektiert werden sollen oder ob Information gewünscht wird über Art und Ausbeute von Radikalen, die sekretiert oder extrazellulär gebildet wurden.
Summary
The attempt to extrapolate radiation chemical in vitro-data of radical reactions to the in vivo-situation meets with severe restrictions. The laws of chemical kinetics are strictly valid only in homogeneous solutions; to arrive at a proper description of radical reactions in complex cellular environments being subdivided by compartment boundaries, one has to rely on model conceptions. From the characteristics which are typical for radical reactions the following statements of general validity may be derived: under the conditions prevailing in vivo, radical chain reactions are intracellularly as well as extracellularly confined to rather limited spatial areas with regard to cellular dimensions. Within short diffusion distances they are bound to react with cellular components, with interstitial fluid or with substances dissolved in the blood, producing radical chain carriers and those peroxidic products which are characteristic for aerobic chain reactions. Only these peroxides are able to diffuse rather freely and thus may react with specific targets — e.g. binding sites of transition metals — to initiate secondary radical chains. This explains why radicals, even though their reactions are intrinsically unspecific, are able to exert “site specific” effects. Only under very special conditions radicals proper are able to cross compartment boundaries. As many of their their peroxidic products are able to do so, nevertheless secondary reactions may occur, which are chemically not discernible from their primary counterpart.
Radical reactions are not necessarily deleterious but can also be used by the cell to fulfill teleogically meaningful metabolic or synthetic purposes.
Amongst the identification methods for radical reactions only the physical procedures of pulse radiolysis and Electron-Spinresonance Spectroscopy offer the possibility to identify radicals directly. Owing to the inherent velocity of radical reactions analytical procedures have to rely on the identification of endproducts of the pertinent chain reactions and to arrive at conclusions in an indirect way. These conclusions must then be corroborated by application of specific scavengers. Furthermore the detection methods have to be modified depending on the goal of either identifying intracellularly generated radicals or of quantifying radicals which are secreted or formed extracellularly.
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Saran, M. (1995). Freie Sauerstoffradikale: Biologische Grundlagen und Nachweismethoden. In: Beger, H.G., Manns, M.P., Greten, H. (eds) Molekularbiologische Grundlagen der Gastroenterologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79782-8_25
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