BIOCHEMISTRY AND PATHOLOGY OF RADICAL-MEDIATED PROTEIN OXIDATION

Radical-mediated damage to proteins may be initiated by electron leaka ge, metal-ion-dependent reactions and autoxidation of lipids and sugar s. The consequent protein oxidation is O-2-dependent, and involves sev eral propagating radicals, notably alkoxylradicals. Its products inclu de several categories of reactive species, and a range of stable produ cts whose chemistry is currently being elucidated. Among the reactive products, protein hydroperoxides can generate further radical fluxes o n reaction with transition-metal ions; protein-bound reductants (notab ly dopa) can reduce transition-metal ions and thereby facilitate their reaction with hydroperoxides; and aldehydes may participate in Schiff -base formation and other reactions. Cells can detoxify some of the re active species, e.g. by reducing protein hydroperoxides to unreactive hydroxides. Oxidized proteins are often functionally inactive and thei r unfolding is associated with enhanced susceptibility to proteinases. Thus cells can generally remove oxidized proteins by proteolysis. How ever, certain oxidized proteins are poorly handled by cells, and toget her with possible alterations in the rate of production of oxidized pr oteins, this may contribute to the observed accumulation and damaging actions of oxidized proteins during aging and in pathologies such as d iabetes, atherosclerosis and neurodegenerative diseases. Protein oxida tion may also sometimes play controlling roles in cellular remodelling and cell growth. Proteins are also key targets in defensive cytolysis and in inflammatory self-damage. The possibility of selective protect ion against protein oxidation (antioxidation) is raised.