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Together, these data demonstrate that removing cysteine causes lethal weight loss and induces adaptive changes in organismal metabolism, including upregulation of Gclc , elevated γ-glutamyl peptides with depletion of CoA and GSH (Fig

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1) are dysregulated in response to the GDH2 gene deletion, or these pathways are unable to generate sufficient glutamate inside the cells and the large pool of free NADP + required to overcome the thermodynamic barrier inherent in using the still present Gdh3, which is usually an anabolic enzyme with a higher affinity for α-ketoglutarate than for glutamate