PROTEIN HYDROPEROXIDES CAN GIVE RISE TO REACTIVE FREE-RADICALS

Proteins damaged by free-radical-generating systems in the presence of oxygen yield relatively long-lived protein hydroperoxides. These hydr operoxides have been shown by e.p.r. spectroscopy to be readily degrad ed to reactive free radicals on reaction with iron(II) complexes. Comp arison of the observed spectra with those obtained with free amino aci d hydroperoxides had allowed identification of some of the protein-der ived radical species (including a number of carbon-centred radicals, a lkoxyl radicals and a species believed to be the CO2 radical anion) an d the elucidation of novel fragmentation and rearrangement processes i nvolving amino acid side chains. In particular, degradation of hydrope roxide functions on the side chain of glutamic acid is shown to result in decarboxylation at the side-chain carboxy group via the formation of the CO, radical anion; the generation of an identical radical from hydroperoxide groups on proteins suggests that a similar process occur s with these molecules. In a number of cases these fragmentation and r earrangement reactions give rise to further reactive free radicals (R( .), O-2(-.)/HO2., CO2-.) which may act as chain-carrying species in pr otein oxidations. These studies suggest that protein hydroperoxides ar e capable of initiating further radical chain reactions both intra- an d inter-molecularly, and provide information on some of the fundamenta l mechanisms of protein alteration and sidechain fragmentation.