Oxidation and disulfide exchange

Oxidation of methionine is particularly favoured under conditions of low pH, and in the presence of various metal ions. Methionine residues on the surface of a protein are obviously particularly susceptible to oxidation. Those buried internally in the protein are less accessible to oxidant. hGH contains three methionine residues (at positions 14, 125 and 170). Studies have found that oxidation of methionine 14 and 125 (the more readily accessible ones) does not greatly effect hGH activity. However, oxidation of all three methionine residues results in almost total inactivation of the molecule. 

Oxidation can be best minimized by replacing the air in the headspace of the final product container with an inert gas such as nitrogen, and/or the addition of antioxidants to the final product. 

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