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NADH produced in the glycolytic pathway is a cofactor for the enzyme methemoglobin reductase, which reverses the oxidation of iron and returns it to the normal reduced (Fe 2+ ) state

Under conditions of hypoxia, nutrient deprivation, or impaired mitochondrial function, cancer cells modulate NADPH and GSH levels through key metabolic pathways such as the pentose phosphate pathway (PPP), FAO, and glutamine metabolism, thereby establishing a metabolicredox feedback loop [39,40,41]

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Since the influx of glutamine across BBB is relatively modest, the majority of CNS glutamine is synthesized endogenously by astrocytes specifically (the amidation of glutamate to glutamine by glutamine synthetase) [37]