Liu Zhenqi, Jahn Linda A, Wei Liping, Long Wen, Barrett Eugene J
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
J Clin Endocrinol Metab. 2002 Dec;87(12):5553-8. doi: 10.1210/jc.2002-020424.
Studies in vitro as well as in vivo in rodents have suggested that amino acids (AA) not only serve as substrates for protein synthesis, but also as nutrient signals to enhance mRNA translation and protein synthesis in skeletal muscle. However, the physiological relevance of these findings to normal humans is uncertain. To examine whether AA regulate the protein synthetic apparatus in human skeletal muscle, we infused an AA mixture (10% Travesol) systemically into 10 young healthy male volunteers for 6 h. Forearm muscle protein synthesis and degradation (phenylalanine tracer method) and the phosphorylation of protein kinase B (or Akt), eukaryotic initiation factor 4E-binding protein 1, and ribosomal protein S6 kinase (p70(S6K)) in vastus lateralis muscle were measured before and after AA infusion. We also examined whether AA affect urinary nitrogen excretion and whole body protein turnover. Postabsorptively all subjects had negative forearm phenylalanine balances. AA infusion significantly improved the net phenylalanine balance at both 3 h (P < 0.002) and 6 h (P < 0.02). This improvement in phenylalanine balance was solely from increased protein synthesis (P = 0.02 at 3 h and P < 0.003 at 6 h), as protein degradation was not changed. AA also significantly decreased whole body phenylalanine flux (P < 0.004). AA did not activate Akt phosphorylation at Ser(473), but significantly increased the phosphorylation of both eukaryotic initiation factor 4E-binding protein 1 (P < 0.04) and p70(S6K) (P < 0.001). We conclude that AA act directly as nutrient signals to stimulate protein synthesis through Akt-independent activation of the protein synthetic apparatus in human skeletal muscle.
对啮齿动物进行的体外和体内研究表明，氨基酸（AA）不仅是蛋白质合成的底物，也是增强骨骼肌中mRNA翻译和蛋白质合成的营养信号。然而，这些发现与正常人类的生理相关性尚不确定。为了研究AA是否调节人类骨骼肌中的蛋白质合成机制，我们将一种氨基酸混合物（10% 凡命）全身输注给10名年轻健康男性志愿者，持续6小时。在输注AA前后，测量了前臂肌肉蛋白质合成与降解（苯丙氨酸示踪法）以及股外侧肌中蛋白激酶B（或Akt）、真核起始因子4E结合蛋白1和核糖体蛋白S6激酶（p70(S6K)）的磷酸化情况。我们还研究了AA是否影响尿氮排泄和全身蛋白质周转。在吸收后状态下，所有受试者的前臂苯丙氨酸平衡均为负值。输注AA后，在3小时（P < 0.002）和6小时（P < 0.02）时，净苯丙氨酸平衡均显著改善。苯丙氨酸平衡的这种改善完全来自蛋白质合成的增加（3小时时P = 0.02，6小时时P < 0.003），因为蛋白质降解没有变化。AA还显著降低了全身苯丙氨酸通量（P < 0.004）。AA未激活Ser(473)位点的Akt磷酸化，但显著增加了真核起始因子4E结合蛋白1（P < 0.04）和p70(S6K)（P < 0.001）的磷酸化。我们得出结论，AA直接作为营养信号，通过不依赖Akt的方式激活人类骨骼肌中的蛋白质合成机制来刺激蛋白质合成。
