White James P
Department of Medicine, Duke University School of Medicine, Durham, NC, United States.
Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, United States.
Front Cell Dev Biol. 2021 May 31;9:656604. doi: 10.3389/fcell.2021.656604. eCollection 2021.
Skeletal muscle protein synthesis is a highly complex process, influenced by nutritional status, mechanical stimuli, repair programs, hormones, and growth factors. The molecular aspects of protein synthesis are centered around the mTORC1 complex. However, the intricacies of mTORC1 regulation, both up and downstream, have expanded overtime. Moreover, the plastic nature of skeletal muscle makes it a unique tissue, having to coordinate between temporal changes in myofiber metabolism and hypertrophy/atrophy stimuli within a tissue with considerable protein content. Skeletal muscle manages the push and pull between anabolic and catabolic pathways through key regulatory proteins to promote energy production in times of nutrient deprivation or activate anabolic pathways in times of nutrient availability and anabolic stimuli. Branched-chain amino acids (BCAAs) can be used for both energy production and signaling to induce protein synthesis. The metabolism of BCAAs occur in tandem with energetic and anabolic processes, converging at several points along their respective pathways. The fate of intramuscular BCAAs adds another layer of regulation, which has consequences to promote or inhibit muscle fiber protein anabolism. This review will outline the general mechanisms of muscle protein synthesis and describe how metabolic pathways can regulate this process. Lastly, we will discuss how BCAA availability and demand coordinate with synthesis mechanisms and identify key factors involved in intramuscular BCAA trafficking.
骨骼肌蛋白质合成是一个高度复杂的过程，受营养状况、机械刺激、修复程序、激素和生长因子影响。蛋白质合成的分子层面以mTORC1复合体为中心。然而，mTORC1上下游调控的复杂性随着时间不断扩展。此外，骨骼肌的可塑性使其成为一种独特的组织，必须在肌纤维代谢的时间变化与组织内具有大量蛋白质的肥大/萎缩刺激之间进行协调。骨骼肌通过关键调节蛋白来管理合成代谢和分解代谢途径之间的推拉，以便在营养缺乏时促进能量产生，或在营养充足和有合成代谢刺激时激活合成代谢途径。支链氨基酸（BCAAs）可用于能量产生和信号传导以诱导蛋白质合成。BCAAs的代谢与能量和合成代谢过程同时发生，在各自途径的几个点上汇聚。肌肉内BCAAs的命运增加了另一层调节，这对促进或抑制肌纤维蛋白质合成代谢有影响。本综述将概述肌肉蛋白质合成的一般机制，并描述代谢途径如何调节这一过程。最后，我们将讨论BCAAs的可用性和需求如何与合成机制协调，并确定参与肌肉内BCAA转运的关键因素。
