Oxidation of methionyl residues in proteins: tools, targets, and reversal.

Methionine (Met) is one of the most readily oxidized amino acid constituents of proteins. It is attacked by H2O2, hydroxyl radicals, hypochlorite, chloramines, and peroxynitrite, all these oxidants being produced in biological systems. The oxidation product, Met sulfoxide, can be reduced back to Met by Met sulfoxide reductase. Numerous proteins lose functional activity by Met oxidation. However, functional activation of proteins by Met oxidation has also been observed. Functional changes by Met oxidation in a given protein appear to have pathophysiological significance in some cases. Considering the reversibility of Met oxidation and the functional changes associated with the oxidation, it seems possible that Met oxidation/reduction in proteins may be one means to control homeostasis in biological systems.