Protein oxidation and turnover

All biomacromolecules are faced with oxidative stress. Oxidation of a protein molecule always induces inactivation of the molecule and introduces a tag to that molecule. These modified protein molecules are prone to degradation in vivo by the proteasome system. Coupling of protein modification and degradation of chemically modified proteins is one of the normal protein turnover pathways in vivo. We call this a 'chemical apoptosis' process, which is one of the early manifestations of programmed cell death. Impairment of the proteasome system leads to accumulation of modified nonfunctional proteins or 'aged proteins' that might cause various clinical syndromes including cataractogenesis, premature aging, neurological degeneration and rheumatoid disease. The metal-catalyzed oxidation of biomacromolecules provides an excellent artificial aging system in vitro. The system is very useful in the characterization of structure and function relationships of proteins (enzymes), especially in those containing metal binding domain(s), because the oxidation is always followed by an affinity cleavage at the metal binding site(s) that allows easy identification and further characterization.