Low S Y, Rennie M J, Taylor P M
Department of Anatomy and Physiology, University of Dundee, Old Medical School, Scotland, U.K.
FASEB J. 1994 Jan;8(1):127-31. doi: 10.1096/fasebj.8.1.7905447.
Glutamine produced and stored in skeletal muscle is an important source of nitrogen and energy for the whole body in health and disease and, unsurprisingly, glutamine turnover in muscle is subject to substantial metabolic control. L-Glutamate, a necessary substrate for glutamine synthetase, is transported into muscle cells by Na(+)-dependent and -independent transport systems. In primary cultures of rat skeletal muscle myotubes (a useful model system for studies of muscle metabolism and membrane transport), Na(+)-dependent glutamate transport (Km approximately 0.7 mM glutamate) shows adaptive upregulation (65% increase in transport Vmax from 2.7 to 4.4 nmol.min-1 x mg protein-1) in cells within 24 h of glutamine depletion (t1/2 for increase of approximately 4 h), whereas Na(+)-independent glutamate uptake remains unaltered. Up-regulation of transport is suppressed by inhibitors of gene transcription (actinomycin-D) and translation (cycloheximide) and is reversed by glutamine supplementation. Increased glutamate transport capacity should provide extra substrate for glutamine synthesis in muscle cells. Thus, in concert with previously discovered increases in cell glutamine transport capacity and glutamine synthetase activity, it may represent part of a co-ordinated response to decreased glutamine availability (e.g., under circumstances of increased glutamine utilization by other tissues in vivo.
在健康和疾病状态下，骨骼肌产生并储存的谷氨酰胺是全身氮和能量的重要来源，不出所料，肌肉中的谷氨酰胺周转受到大量代谢控制。L-谷氨酸是谷氨酰胺合成酶的必需底物，通过依赖Na⁺和不依赖Na⁺的转运系统转运到肌肉细胞中。在大鼠骨骼肌肌管的原代培养物（一种用于研究肌肉代谢和膜转运的有用模型系统）中，依赖Na⁺的谷氨酸转运（谷氨酸的Km约为0.7 mM）在谷氨酰胺耗竭24小时内（增加的t1/2约为4小时）细胞中显示出适应性上调（转运Vmax从2.7增加到4.4 nmol·min⁻¹·mg蛋白⁻¹，增加65%），而不依赖Na⁺的谷氨酸摄取保持不变。转运的上调受到基因转录抑制剂（放线菌素-D）和翻译抑制剂（环己酰亚胺）的抑制，并通过补充谷氨酰胺而逆转。增加的谷氨酸转运能力应为肌肉细胞中的谷氨酰胺合成提供额外的底物。因此，与先前发现的细胞谷氨酰胺转运能力和谷氨酰胺合成酶活性的增加相一致，它可能代表对谷氨酰胺可用性降低的协调反应的一部分（例如，在体内其他组织对谷氨酰胺利用增加的情况下）。
