Markers of protein oxidation: different oxidants give rise to variable yields of bound and released carbonyl products

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Henrietta A Headlam, Michael Jonathan Davies

Exposure of proteins to radicals in the presence of O2 gives both side-chain oxidation and backbone fragmentation. These processes can be interrelated, with initial side-chain oxidation giving rise to backbone damage via transfer reactions. We have shown previously that alkoxyl radicals formed on the C-3 carbons of Ala, Val, Leu, and Asp residues undergo beta-scission to give backbone alpha-carbon radicals, with the release of the side- chain as a carbonyl compound. We now show that this is a general mechanism that occurs with a wide range of oxidants. The quantitative significance of this process depends on the extent of oxidation at C-3 compared with other sites. HO*, generated by gamma radiolysis, gave the highest total carbonyl yield, with protein-bound carbonyls predominating over released. In contrast, metal ion/H2O2 systems, gave more released than bound carbonyls, with this ratio modulated by EDTA. This is ascribed to metal ion-protein interactions affecting the sites of initial oxidation. Hypochlorous acid gave low concentrations of released carbonyls, but high yields of protein-bound material. The peroxyl radical generator 2,2'-azobis(2-amidinopropane) hydrochloride, and a peroxynitrite generator, 3-morpholinosydnonimine hydrochloride, gave lower overall carbonyl yields, with released carbonyls predominating over protein-bound species similar to that observed with metal ion/H2O2 systems.

Original languageEnglish
JournalFree Radical Biology & Medicine
Volume36
Issue number9
Pages (from-to)1175-84
Number of pages10
ISSN0891-5849
DOIs
Publication statusPublished - 2004

    Research areas

  • Acetone, Aldehydes, Formaldehyde, Glyoxylates, Hydrogen Peroxide, Metals, Oxidants, Oxidation-Reduction, Proteins, Serum Albumin, Bovine

ID: 138273473