Austgen T R, Chakrabarti R, Chen M K, Souba W W
Department of Surgery, University of Florida College of Medicine, Gainesville.
J Trauma. 1992 May;32(5):600-6; discussion 606-7. doi: 10.1097/00005373-199205000-00011.
The effects of a single dose of endotoxin (7.5 mg/kg BW) on skeletal muscle glutamine metabolism were studied in vivo in rats to gain further understanding of the altered glutamine metabolism that characterizes sepsis and other catabolic diseases. In endotoxin-treated animals the arterial glutamine concentration fell early initially and then increased compared with control values. Twelve hours after treatment, the arteriovenous concentration difference for glutamine across the hindquarter doubled, resulting in a significant increase in net muscle glutamine release in endotoxin-treated rats. As a consequence, the muscle glutamine concentration fell in the endotoxin-treated animals by 25%-40%, an event that was apparent as early as two hours after endotoxin treatment. Skeletal muscle glutaminase activity, the major enzyme of glutamine breakdown, was unchanged by endotoxemia, but expression of glutamine synthetase mRNA and glutamine synthetase specific activity increased in a time-dependent fashion. The glutamine depletion that develops in skeletal muscle during endotoxemia is caused by accelerated muscle glutamine release rather than an increase in intracellular degradation or a fall in intracellular biosynthesis. The adaptive increase in glutamine synthetase expression that occurs requires de novo RNA and protein synthesis and may be designed to prevent complete depletion of the intracellular glutamine pool.
为了进一步了解脓毒症和其他分解代谢性疾病所特有的谷氨酰胺代谢改变，在大鼠体内研究了单剂量内毒素（7.5毫克/千克体重）对骨骼肌谷氨酰胺代谢的影响。在内毒素处理的动物中，动脉谷氨酰胺浓度最初早期下降，然后与对照值相比升高。处理后12小时，后肢谷氨酰胺的动静脉浓度差增加了一倍，导致内毒素处理的大鼠肌肉净谷氨酰胺释放显著增加。结果，内毒素处理的动物肌肉谷氨酰胺浓度下降了25%-40%，这一现象在内毒素处理后两小时就很明显。骨骼肌谷氨酰胺酶活性是谷氨酰胺分解的主要酶，内毒素血症对其没有影响，但谷氨酰胺合成酶mRNA的表达和谷氨酰胺合成酶的比活性呈时间依赖性增加。内毒素血症期间骨骼肌中发生的谷氨酰胺消耗是由肌肉谷氨酰胺释放加速引起的，而不是细胞内降解增加或细胞内生物合成减少。谷氨酰胺合成酶表达的适应性增加需要从头合成RNA和蛋白质，可能是为了防止细胞内谷氨酰胺池完全耗尽。
