Girard G, Butterworth R F
Laboratory of Neurochemistry, André-Viallet Clinical Research Center, Hôpital St-Luc (University of Montreal), Quebec, Canada.
Dig Dis Sci. 1992 Jul;37(7):1121-6. doi: 10.1007/BF01300297.
Glutamine synthetase is responsible for the ATP-dependent amidation of glutamate to glutamine. In liver the enzyme is highly localized in perivenous hepatocytes; in brain the enzyme is localized in astrocytes. Portacaval anastomosis resulted in liver atrophy, hyperammonemia, and up to 90% loss of glutamine synthetase activity in liver homogenates. This effect, which appears to be irreversible, probably reflects the selective loss of perivenous hepatocytes following portacaval anastomosis. Glutamine synthetase activities in brain were unaffected by portacaval anastomosis of up to 12 weeks' duration. Enzyme activities in homogenates of skeletal muscle, on the other hand, were significantly increased at one and four weeks after shunt surgery. These effects were not the result of decreased food intake in shunted animals. These findings suggest fundamentally different regulatory mechanisms for glutamine synthetase in these tissues. Skeletal muscle may thus provide an important alternative site for ammonia detoxification after portal-systemic shunting.
谷氨酰胺合成酶负责将谷氨酸在ATP的作用下酰胺化为谷氨酰胺。在肝脏中，该酶高度定位于肝小叶中央静脉周围的肝细胞；在大脑中，该酶定位于星形胶质细胞。门腔静脉吻合术导致肝脏萎缩、高氨血症，并且肝脏匀浆中谷氨酰胺合成酶活性丧失高达90%。这种效应似乎是不可逆的，可能反映了门腔静脉吻合术后肝小叶中央静脉周围肝细胞的选择性丧失。长达12周的门腔静脉吻合术对大脑中的谷氨酰胺合成酶活性没有影响。另一方面，分流手术后1周和4周时，骨骼肌匀浆中的酶活性显著增加。这些效应并非分流动物食物摄入量减少所致。这些发现表明这些组织中谷氨酰胺合成酶的调节机制存在根本差异。因此，骨骼肌可能是门体分流术后氨解毒的一个重要替代部位。
