Amino acid signalling and the integration of metabolism

Biochem Biophys Res Commun. 2004 Jan 9;313(2):397-403. doi: 10.1016/j.bbrc.2003.07.012.


It has become clear in recent years that amino acids are not only important as substrates for various metabolic pathways but that they can also activate a nutrient-sensitive, mTOR-mediated, signalling pathway in synergy with insulin. Leucine is the most effective amino acid in this regard. The signalling pathway is antagonised by AMP-activated protein kinase. Amino acid signalling stimulates protein synthesis and inhibits (autophagic) proteolysis. In addition, many amino acids cause an increase in cell volume. Cell swelling per se stimulates synthesis of protein, glycogen, and lipid, in part by further stimulating signalling and in part by unrelated mechanisms. Amino acids also stimulate signalling in beta-cells and stimulate beta-cell growth and proliferation. This results in increased production of insulin, which enhances the anabolic (and anti-catabolic) properties of amino acids. Finally, amino acid-dependent signalling controls the production of leptin by adipocytes, and thus contributes to the regulation of appetite.

Publication types

  • Review

MeSH terms

  • Amino Acids / physiology*
  • Animals
  • Cell Size / physiology
  • Energy Metabolism
  • Humans
  • Insulin / metabolism
  • Islets of Langerhans / growth & development
  • Islets of Langerhans / metabolism
  • Protein Kinases / metabolism
  • Proteins / metabolism*
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases


  • Amino Acids
  • Insulin
  • Proteins
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases