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96,97 Moreover, the ME1 protein is hypophosphorylated at S336 and hyperacetylated at K337 by PGAM family member 5 and acetyl-CoA acetyltransferase, respectively, resulting in ME1 translocation from mitochondria to the cytosol, dimerization and activation, thus strongly promoting NADPH generation and tumorigenesis

FIGURE 8 The aforementioned abnormalities at the molecular level (downregulation of the Nrf2/HO-1 axis and GPX4) and subcellular structural level (neuronal somata and mitochondrial impairment) were consistent with the GSH metabolism perturbations identified by multi-omics analyses, collectively reflecting oxidative stress-associated damage in the hippocampus during SAE

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While adequate folate intake appears protective before malignant change occurs, excessive folic acid exposure, particularly in susceptible individuals with reduced DHFR activity, may not always be desirable