General mechanism of MSR and regeneration by the thioredoxin system. Reduction of methionine sulfoxide to methionine by MSR results in the transient formation of an intramolecular disulfide bond that inactivates the enzyme. Disulfide exchange reaction with thioredoxin (TRX) regenerates the active form of MSR and leads to inactivation of TRX. Regeneration of reduced TRX occurs through a transfer of electrons from NADPH in a reaction catalyzed by thioredoxin reductase (TR). The active reduced forms of the enzymes are depicted in yellow and the inactive oxidized forms of enzymes in gray.