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The two-step synthesis of the glutathione tripeptide requires two ATP-dependent enzymes, namely glutamate cysteine ligase (GCL/-ECS/CAD2/GSH1) and glutathione synthetase (GSH2) (Mller-Schssele et al., 2020)

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In response to OS, different metabolites oxidize highly reactive cysteine residues in KEAP1, inducing a conformational change in the KEAP1-NEDD8-CUL3-RBX1-E3 ubiquitin ligase complex, with an improper orientation of Lys residues on NRF2 [122, 158]

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