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6.1 Glutathione metabolism: modern view of biosynthetic pathways, NADPH dependence, and relationship to thioredoxin The synthesis of glutathione (GSH) predominantly occurs through the ATP-dependent -glutamyl cycle, beginning with the action of glutamate-cysteine ligase (GCL), the key rate-limiting enzyme composed of two subunits: a catalytic component (GCLC) and a regulatory modifier (GCLM)

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