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It is interesting that preventing glutamine degradation in brain mitochondria and glutamine uptake can ameliorate brain damage in HE.46 According to Detry et al., it can be hypothesized that brain edema secondary to the osmotic effect of glutamine in astrocytes, and cerebral hyperemia, secondary to vasodilation (cytokines, products of the necrotic liver, glutamine and others) may contribute to intracranial hypertension leading to brain stem herniation and brain death in fulminant hepatic failure.47 Glutamine synthetase Glutamine synthetase (GS) is a key enzyme in glutamate metabolism (Figure 2), and its decreased activity leads to glutamate increases in the extracellular space