Reactions of Peroxynitrite with Biomolecules

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2000
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Daiber, Andreas
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Titel in einer weiteren Sprache
Reaktionen von Peroxynitrit mit Biomolekülen
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Zusammenfassung

Peroxynitrite (PN) is formed in vivo in the reaction of nitric oxide (NO) with superoxide. PN is a powerful oxidant, which nitrates and hydroxylates phenols, but also leads to dimerization of such compounds. In this work some new products formed in the reaction of phenol with PN could be identified. Moreover the results of some experiments pointed towards a radical mechanism and the involvement of phenoxy radicals in this radical pathway. In a second part of this work several scavengers were tested for their efficiency to scavenge PN and inhibit harmful reactions with biotargets, such as the oxidation and inactivation of ADH, the nitration of phenol (as a model for tyrosine) and the nitration of BSA-bound tyrosines. For each of these reactions a number of antioxidants were employed and their IC50 values for the inhibition in these reactions were determined. In the last chapter the nitration by PN was investigated within two P450 enzymes: P450-BM3 and P450-CAM. These studies revealed that the nitration of some tyrosine residues is autocatalytic and therefore highly sensitive and selective. Moreover a ferryl (Compound II) spectrum could be observed for several P450 proteins, suggesting that it must be an obligatory and common intermediate in reactions of PN with P450 enzymes.

Zusammenfassung in einer weiteren Sprache

Peroxynitrit (PN) wird im Organismus in der Reaktion von Stickstoffmonoxid (NO) mit Superoxid gebildet. PN ist eine stark oxidierende Verbindung, die Phenole nitriert und hydroxyliert, sowie zu Dimerisierungsprodukten führt. Einige neue Produkte wurden in der Reaktion von Peroxynitrit mit Phenol identifiziert, sowie Versuche durchgeführt, die auf Phenoxyradikale als Intermediat hindeuten. Eine Vielzahl von Hemmstofen für verschiedene Reaktionen von PN (Oxidation und Inaktivierung von Alkohol Dehydrogenase, Nitrierung von Phenol, Nitrierung von BSA) wurden ausgetestet und IC50 Werte für die jeweilige inhibierte Reaktion bestimmt. An zwei speziellen Enzymen wurde die Nitrierung von Tyrosinresten in Proteinen untersucht und eine Metallkatalyse für die selektive und sensitive Nitrierung bestimmter Tyrosinreste in P450-BM3 und P450-CAM durch PN aufgedeckt. In stopped-flow Experimenten konnte ein Ferryl (Compound II) Intermediat in diesen Häm-Thiolat Proteinen während der Reaktion beobachtet werden.

Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
Peroxynitrit, Superoxid, P450 Enzyme, Hydroxylierung, Antioxidantien, peroxynitrite, superoxide, P450 enzymes, hydroxylation, antioxidants
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Zitieren
ISO 690DAIBER, Andreas, 2000. Reactions of Peroxynitrite with Biomolecules [Dissertation]. Konstanz: University of Konstanz
BibTex
@phdthesis{Daiber2000React-8252,
  year={2000},
  title={Reactions of Peroxynitrite with Biomolecules},
  author={Daiber, Andreas},
  note={Teile der Arbeit sind auch erschienen in:<br /> Nitric Oxide: Biology and Chemistry 1998 and 1999, Biochem. Pharmacol. 2000, Arch. Biochem. Biophys. 2000},
  address={Konstanz},
  school={Universität Konstanz}
}
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June 8, 2000
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Teile der Arbeit sind auch erschienen in:
Nitric Oxide: Biology and Chemistry 1998 and 1999, Biochem. Pharmacol. 2000, Arch. Biochem. Biophys. 2000
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