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In this process, a reduction of SOD1 Cu 2+ by H 2 O 2 (Reaction 3) is followed by a Cu + oxidation by another H 2 O 2 in a Fenton-type reaction to generate a hydroxyl radical (Reaction 4) 51,92,93 : The hydroxyl radical formation is markedly accelerated in the fALS SOD1 mutants, as compared with the native SOD1 WT , a feature attributed to structural instability of the former manifested in the increased openness and accessibility of the active-site Cu 2+ to substrates other than superoxide 35,51,95