Conigrave A D, Franks A H, Brown E M, Quinn S J
School of Molecular and Microbial Biosciences, University of Sydney, NSW, Australia.
Eur J Clin Nutr. 2002 Nov;56(11):1072-80. doi: 10.1038/sj.ejcn.1601463.
Cellular sensing of L-amino acids is widespread and controls diverse cellular responses regulating, for example, rates of hormone secretion, amino acid uptake, protein synthesis and protein degradation (autophagy). However, the nature of the sensing mechanisms involved has been elusive. One important sensing mechanism is selective for branched chain amino acids, acts via mTOR (mammalian target of rapamycin) and regulates the rates of insulin and IGF-1 secretion as well as hepatic, and possibly muscle, autophagy. A second sensing mechanism is selective for aromatic L-amino acids and regulates the rate of gastric acid secretion and other responses in the gastro-intestinal tract. Interactions between calcium and protein metabolism, including accelerated urinary calcium excretion in subjects consuming high-protein diets and secondary hyperparathyroidism in subjects consuming low-protein diets, suggest an additional amino acid sensing mechanism linked to the control of urinary calcium excretion and parathyroid hormone (PTH) release. New data demonstrating L-amino acid-dependent activation of the calcium-sensing receptor (CaR), which regulates PTH secretion and urinary calcium excretion, suggests an unexpected explanation for these links between calcium and protein metabolism. Furthermore, expression of the CaR in gastrin-secreting G-cells and acid-secreting parietal cells, together with data indicating that the CaR exhibits selectivity for aromatic amino acids, would appear to provide a molecular explanation for amino acid sensing in the gastrointestinal tract. This review examines what is known about the CaR as a gene, a receptor, a physiological regulator and, now, as an amino acid sensor. Possible new roles for the CaR are also considered.
细胞对L-氨基酸的感知广泛存在，并控制着多种细胞反应，例如调节激素分泌速率、氨基酸摄取、蛋白质合成和蛋白质降解（自噬）。然而，所涉及的感知机制的本质一直难以捉摸。一种重要的感知机制对支链氨基酸具有选择性，通过mTOR（雷帕霉素哺乳动物靶标）起作用，并调节胰岛素和IGF-1的分泌速率以及肝脏和可能的肌肉自噬。第二种感知机制对芳香族L-氨基酸具有选择性，并调节胃酸分泌速率和胃肠道中的其他反应。钙与蛋白质代谢之间的相互作用，包括高蛋白饮食受试者尿钙排泄加速以及低蛋白饮食受试者继发性甲状旁腺功能亢进，提示存在一种与尿钙排泄控制和甲状旁腺激素（PTH）释放相关的额外氨基酸感知机制。新数据表明L-氨基酸依赖性激活钙敏感受体（CaR），该受体调节PTH分泌和尿钙排泄，这为钙与蛋白质代谢之间的这些联系提供了意想不到的解释。此外，CaR在分泌胃泌素的G细胞和分泌酸的壁细胞中的表达，以及表明CaR对芳香族氨基酸具有选择性的数据，似乎为胃肠道中的氨基酸感知提供了分子解释。本综述探讨了关于CaR作为一种基因、一种受体、一种生理调节剂以及现在作为一种氨基酸传感器的已知信息。还考虑了CaR可能的新作用。
