Among surviving patients, the most severely affected patients have intellectual disability, progressive cerebellar disease and ataxia, recurrent bacterial infections, and chronic metabolic acidosis and hemolytic anemia
Interest broadened sharply after Yang and colleagues (Cell, 2014) used targeted metabolomic profiling across twelve ferroptosis-inducing small molecules and found that glutathione depletion converges on inactivation of the selenoenzyme glutathione peroxidase 4, placing glutathione availability directly upstream of iron-dependent lipid peroxidation
Glutathione is synthesized in the cytosol of each cell by the action of two enzymes in an elegantly regulated system that allows it to be maintained at different homeostatic levels in different tissue types, with the liver, given its detoxification role, having the highest amounts
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