Elevated blood ammonia (hyperammonemia) is believed to be a major contributor to the neurological sequelae following severe liver disease. Ammonia is cleared via two main mechanisms, the urea cycle pathway and the glutamine synthetase reaction. Recent studies of genetically modified animals confirm the importance of the urea cycle, but also suggest that the glutamine synthetase reaction is more important than previously recognized. While the liver clears about two-thirds of the body's ammonia via the combined action of the urea cycle and glutamine synthetase, extrahepatic tissues do not express all the components required for performing a complete urea cycle and therefore depend on the glutamine synthetase reaction for ammonia clearance. The brain is particularly vulnerable to the effects of hyperammonemia, which include impaired extracellular potassium buffering and brain edema. Moreover, the glutamine synthetase reaction is intimately linked to the metabolism of the excitatory and inhibitory neurotransmitters glutamate and gamma aminobutyric acid (GABA), implicating a key role for this enzyme in neurotransmission. This review discusses the emerging roles of glutamine synthetase in brain pathophysiology, particularly aspects related to ammonia homeostasis and hepatic encephalopathy.

血氨升高（高氨血症）被认为是严重肝病后神经系统后遗症的主要原因。氨通过两种主要机制清除，尿素循环途径和谷氨酰胺合成酶反应。最近对转基因动物的研究证实了尿素循环的重要性，但也表明谷氨酰胺合成酶反应比以前认识到的更重要。虽然肝脏通过尿素循环和谷氨酰胺合成酶的联合作用清除体内约三分之二的氨，但肝外组织并不表达完成完整尿素循环所需的所有成分，因此依赖谷氨酰胺合成酶反应来清除氨. 大脑特别容易受到高氨血症的影响，其中包括细胞外钾缓冲受损和脑水肿。此外，谷氨酰胺合成酶反应与兴奋性和抑制性神经递质谷氨酸和 γ 氨基丁酸 (GABA) 的代谢密切相关，暗示这种酶在神经传递中的关键作用。本综述讨论了谷氨酰胺合成酶在脑病理生理学中的新作用，特别是与氨稳态和肝性脑病相关的方面。