Redox modifications of reactive cysteine residues by H2O2. Redox-sensitive proteins contain cysteine residues, which are partially ionized under physiological pH. Oxidation of this thiolate anion (1) results in a sulfenic acid or rather its salt (2), which is relatively reactive and forms intra-/intermolecular disulfide bonds in the presence of thiolate. This sulfenylation can be intramolecular or intermolecular (3), the latter predominantly with GSH to form glutathionylated intermediates (5), or sulfenylamides with oxidizable amines (4) and glutathionylated intermediates (5), respectively. These redox modifications result in altered functions of their target proteins and can be reversed by the Trx- or GSH-based anti-oxidative systems. Under excessive H2O2 concentration the sulfonate or sulfonamide intermediates can be further irreversibly oxidized to sulfinic (6) and sulfonic acids (7) forming the respective anions under physiological pH thus also shifting the isoelectric points of affected proteins.