Oxidative Damage to Proteins

Any oxidative stress that reaches the cytosol can lead to the disruption of lipid bilayers, changes in conductivity, disturbances to proton gradients, and to higher functional protein sensitivity in general. Amino acids vary considerably in terms of their binding and reactivity with radicals.

In particular, metal-containing amino acids and the thiol groups of the proteins are very sensitive. Activated oxygen can extract a hydrogen atom (H+) from cysteine to form a thiol radical, which can then bond with other cysteines via a disulfide bond. Alternatively, oxygen can bond with methionine residues, so that methionine-sulfur derivatives are formed. The oxidation of iron-sulfur centres via superoxide disturbs enzymatic function (Gardner and Fridovich 1991). When several amino acids are modified by radicals, the protein is oxidised.

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