Physiological concentrations of ascorbate cannot prevent the potentially damaging reactions of protein radicals in humans

Thomas Nauser, Janusz M. Gebicki*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    12 Citations (Scopus)

    Abstract

    The principal initial biological targets of free radicals formed under conditions of oxidative stress are the proteins. The most common products of the interaction are carbon-centered alkyl radicals which react rapidly with oxygen to form peroxyl radicals and hydroperoxides. All these species are reactive, capable of propagating the free radical damage to enzymes, nucleic acids, lipids, and endogenous antioxidants, leading finally to the pathologies associated with oxidative stress. The best chance of preventing this chain of damage is in early repair of the protein radicals by antioxidants. Estimate of the effectiveness of the physiologically significant antioxidants requires knowledge of the antioxidant tissue concentrations and rate constants of their reaction with protein radicals. Previous studies by pulse radiolysis have shown that only ascorbate can repair the Trp and Tyr protein radicals before they form peroxyl radicals under physiological concentrations of oxygen. We have now extended this work to other protein C-centered radicals generated by hydroxyl radicals because these and many other free radicals formed under oxidative stress can produce secondary radicals on virtually any amino acid residue. Pulse radiolysis identified two classes of rate constants for reactions of protein radicals with ascorbate, a faster one in the range (9-60) × 107 M-1 s-1 and a slow one with a range of (0.5-2) × 107 M-1 s-1. These results show that ascorbate can prevent further reactions of protein radicals only in the few human tissues where its concentration exceeds about 2.5 mM.

    Original languageEnglish
    Pages (from-to)1702-1710
    Number of pages9
    JournalChemical Research in Toxicology
    Volume30
    Issue number9
    DOIs
    Publication statusPublished - 18 Sept 2017

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