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L-Amino acid sensing by the calcium-sensing receptor: a general mechanism for coupling protein and calcium metabolism?

European Journal of Clinical Nutrition volume 56, pages 1072–1080 (2002)Cite this article

An Erratum to this article was published on 24 June 2003

Abstract

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.

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Acknowledgements

The authors' research is supported by the NH&MRC of Australia and the NIH of the USA (DK41415, 48330 and 52005).

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  1. AD Conigrave: Guarantor: AD Conigrave.

  2. AD Conigrave, AH Franks, EM Brown and SJ Quinn: Contributors: ADC developed the theoretical framework with EMB and SJQ. AHF assisted ADC with writing the MS which was checked for accuracy by EMB and SJQ.

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  1. School of Molecular and Microbial Biosciences, University of Sydney, NSW, Australia

    AD Conigrave & AH Franks

  2. Endocrine-Hypertension Division and Membrane Biology Program, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA

    EM Brown & SJ Quinn

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Conigrave, A., Franks, A., Brown, E. et al. L-Amino acid sensing by the calcium-sensing receptor: a general mechanism for coupling protein and calcium metabolism?. Eur J Clin Nutr 56, 1072–1080 (2002). https://doi.org/10.1038/sj.ejcn.1601463

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