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When PLOOH is not rapidly neutralized as an PLOH by glutathione peroxidase 4 (GPX4) in time, PLOOH further reacts with ferrous ions, and the resulting lipid radicals, such as alkoxyl phospholipid radicals (PLO•) and PLOO•, react with PUFA-PLs ( 2 − produced by the mitochondrial tricarboxylic acid (TCA) cycle and the reduction of nitrogen oxides by NADPH produce H 2 O 2 catalyzed by superoxide dismutase (SOD) and participate in the Fenton reaction of iron ( Figure 1A )
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In the Walsh framework, toxic overload is one biochemical pattern that may coexist with undermethylation, copper imbalance, pyroluria or other contributors
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