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Upon binding to an uncharged tRNA, GCN2 undergoes a conformational change and is activated, resulting in inhibitory phosphorylation of eukaryotic translation initiation factor 2 (eIF2), preventing translation initiation under amino acid deficiency (Figure 1) (Berlanga et al., 1999

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In my own practice, especially if an older person has risk factors for vitamin B12 deficiency, I consider a vitamin B12 level of 200-400 pg/mL borderline, and I usually order a methylmalonic acid level as a follow-up