Division of Cell Signalling & Immunology, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee, UK.
Curr Opin Clin Nutr Metab Care. 2013 Jan;16(1):57-65. doi: 10.1097/MCO.0b013e32835a885c.
We consider recent advances in epithelial amino acid transport physiology and our understanding of the functioning of amino acid transporters as sensors, as well as carriers, of tissue nutrient supplies.
Gut hormones (e.g. leptin) may regulate intestinal amino acid transporter activity by a variety of mechanisms, although the overall functional significance of such regulation is not yet fully understood. Important functional interactions between amino acid transporters and nutrient-signalling pathways which regulate metabolism [e.g. the mammalian target of rapamycin (mTOR)C1 pathway which promotes cell growth] have been revealed in recent studies. Amino acid transporters on endosomal (e.g. lysosomal) membranes may be of unexpected significance as intracellular nutrient sensors. It is also now evident that certain amino acid transporters may have dual receptor-transporter functions and act as 'transceptors' to sense amino acid availability upstream of signal pathways.
Increased knowledge on the timescale of the amino acid sensor-signal-effector process(es) should help in the optimization of protein-feeding regimes to gain maximum anabolic effect. New opportunities for nutritional therapy include targeting of amino acid transceptors to promote protein-anabolic signals and mechanisms up-regulating amino acid transporter expression to improve absorptive capacity for nutrients.
我们考虑了上皮氨基酸转运生理学的最新进展,以及我们对氨基酸转运体作为组织营养供应传感器和载体的理解。
肠道激素(例如瘦素)可能通过多种机制调节肠道氨基酸转运体的活性,但这种调节的整体功能意义尚不完全清楚。在最近的研究中,揭示了氨基酸转运体与调节代谢的营养信号通路(例如促进细胞生长的哺乳动物雷帕霉素靶蛋白(mTOR)C1 通路)之间的重要功能相互作用。内体(例如溶酶体)膜上的氨基酸转运体可能作为细胞内营养传感器具有意想不到的意义。现在也很明显,某些氨基酸转运体可能具有双重受体-转运体功能,并作为“转导子”在信号通路的上游感知氨基酸的可用性。
增加对氨基酸传感器-信号-效应器过程的时间尺度的了解,应该有助于优化蛋白质喂养方案,以获得最大的合成代谢效果。营养治疗的新机会包括靶向氨基酸转导子以促进蛋白质合成代谢信号和机制,上调氨基酸转运体表达以提高营养物质的吸收能力。