Skip to main content
Log in

Glutamate: a truly functional amino acid

  • Review Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

Glutamate is one of the most abundant of the amino acids. In addition to its role in protein structure, it plays critical roles in nutrition, metabolism and signaling. Post-translational carboxylation of glutamyl residues increases their affinity for calcium and plays a major role in hemostasis. Glutamate is of fundamental importance to amino acid metabolism, yet the great bulk of dietary glutamate is catabolyzed within the intestine. It is necessary for the synthesis of key molecules, such as glutathione and the polyglutamated folate cofactors. It plays a major role in signaling. Within the central nervous system, glutamate is the major excitatory neurotransmitter and its product, GABA, the major inhibitory neurotransmitter. Glutamate interaction with specific taste cells in the tongue is a major component of umami taste. The finding of glutamate receptors throughout the gastrointestinal tract has opened up a new vista in glutamate function. Glutamate is truly a functional amino acid.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Akiba Y, Kaunitz JD (2011) Luminal chemosensing in the duodenal mucosa. Acta Physiol 201:77–84

    Article  CAS  Google Scholar 

  • Battezzati A, Brillon DJ, Matthews DE (1995) Oxidation of glutamic acid by the splanchnic bed in humans. Am J Physiol 269:E269–E276

    PubMed  CAS  Google Scholar 

  • Berkner KL (2000) The vitamin K-dependent carboxylase. J Nutr 130:1877–1880

    PubMed  CAS  Google Scholar 

  • Berkner KL (2005) The vitamin K-dependent carboxylase. Annu Rev Nutr 25:127–149

    Article  PubMed  CAS  Google Scholar 

  • Brosnan JT (2000) Glutamate, at the interface between amino acid and carbohydrate metabolism. J Nutr 130:988S–990S

    PubMed  CAS  Google Scholar 

  • Brosnan ME, Brosnan JT (2009) Hepatic glutamate metabolism: a tale of 2 hepatocytes. Am J Clin Nutr 90:857S–861S

    Article  PubMed  CAS  Google Scholar 

  • Burrin DG, Stoll B (2009) Metabolic fate and function of dietary glutamate in the gut. Am J Clin Nutr 90:850S–856S

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Gabitto M, Peng Y, Ryba NJP, Zuker CS (2011) A gustotopic map of taste qualities in the mammalian brain. Science 333:1262–1266

    Article  PubMed  CAS  Google Scholar 

  • Chu P, Huang T-Y, Williams J, Stafford DW (2006) Purified vitamin K epoxide reductase alone is sufficient for conversion of vitamin K epoxide to vitamin K and vitamin K to vitamin KH2. Proc Natl Acad Sci USA 103:19308–19313

    Article  PubMed  CAS  Google Scholar 

  • Gécz J (2010) Glutamate receptors and learning and memory. Nat Genet 42:925–926

    Article  PubMed  Google Scholar 

  • Höfer D, Püschel B, Drenckhahn (1996). Taste receptor-like cells in the rat gut identified by expression of alpha-gustducin. Proc Nat Acad Sci USA 93:6631–6634

  • Ingram VM (1957) Gene mutation in human haemoglobin: the chemical difference between normal and sickle cell haemoglobin. Nature 180:326–328

    Article  PubMed  CAS  Google Scholar 

  • Janke C, Bulinski JC (2011) Post-translational regulation of the microtubule cytoskeleton: mechanisms and functions. Nat Rev Mol Cell Biol 12:773–786

    Article  PubMed  CAS  Google Scholar 

  • Kanaoka Y, Boyce JA (2004) Cysteinyl leukotrienes and their receptors: cellular distribution and function in immune and inflammatory responses. J Immunol 173:1503–1510

    PubMed  CAS  Google Scholar 

  • Kew JNC, Kemp JA (2005) Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology 179:4–29

    Article  PubMed  CAS  Google Scholar 

  • Kitamura A, Tsurugizawa T, Torii K (2011) Biological significance of glutamate signaling during digestion of food through the gut–brain axis. Digestion 83:37–43

    Article  PubMed  CAS  Google Scholar 

  • Lu SC (2009) Regulation of glutathione synthesis. Mol Aspects Med 30:42–59

    Article  PubMed  CAS  Google Scholar 

  • Matthews DE, Marano MA, Campbell RG (1993) Splanchnic bed utilization of glutamine and glutamic acid in humans. Am J Physiol 264:E848−E854

    Google Scholar 

  • Matousek WM, Ciani B, Fitch CA, Garcia-Moreno B, Kammerer RA, Alexandrescu AT (2007) Electrostatic contributions to the stability of the GCN4 leucine zipper structure. J Mol Biol 374:206–219

    Article  PubMed  CAS  Google Scholar 

  • Meister A, Anderson ME (1983) Glutathione. Ann Rev Biochem 52:711–760

    Article  PubMed  CAS  Google Scholar 

  • Nedergaard M, Takano T, Hansen AJ (2002) Beyond the role of glutamate as a neurotransmitter. Nat Rev Neurosci 3:748–755

    Article  PubMed  CAS  Google Scholar 

  • Nelson G, Chandrashekar J, Hoon MA, Feng L, Zhao G, Ryba NJP, Zuker CS (2002) An amino acid taste receptor. Nature 416:199–202

    Article  PubMed  CAS  Google Scholar 

  • Reeds PJ, Burrin DG, Jahoor F, Wykes L, Henry J, Frazer EM (1996) Enteral glutamate is almost completely metabolized in first pass by the gastrointestinal tract of infant pigs. Am J Physiol 270:E413–418

    PubMed  CAS  Google Scholar 

  • Riedijk MA, de Gast-Bakker DA, Wattimena JL, van Goudoever JB (2007) Splanchnic oxidation is the major metabolic fate of dietary glutamate in enterally fed preterm infants. Pediatr Res 62:468–473

    Article  PubMed  CAS  Google Scholar 

  • Rodgers DW, Crepeau RH, Edelstein SJ (1987) Pairings and polarities of the 14 strands in sickle cell hemoglobin fibers. Proc Natl Acad Sci USA 84:6157–6161

    Article  PubMed  CAS  Google Scholar 

  • Rotter M, Yosmanvich D, Briehl RW, Kwong S, Ferrone FA (2011) Nucleation of sickle hemoglobin mixed with hemoglobin A: experimental and theoretical studies of hybrid-forming mixtures. Biophys J 101:2790–2797

    Article  PubMed  CAS  Google Scholar 

  • Schubert F, Gallinat J, Seifert F, Rinneberg H (2004) Glutamate concentrations in human brain using single voxel proton magnetic resonance spectroscopy at 3 Tesla. Neuroimage 21:1762–1771

    Article  PubMed  Google Scholar 

  • Sengupta JN, Petersen J, Peles S, Shaker R (2004) Response properties of antral mechanosensitive afferent fibers and effects of ionotropic glutamate receptor antagonists. Neurosci 125:711–723

    Article  CAS  Google Scholar 

  • Stanley CA (2004) Hyperinsulinemia/hyperammonemia syndrome: insights into the regulatory role of glutamate dehydrogenase in ammonia metabolism. Mol Genet Metab 81:S45–S51

    Article  PubMed  CAS  Google Scholar 

  • Stanley CA (2009) Regulation of glutamate metabolism and insulin secretion by glutamate dehydrogenase in hypoglycaemic children. Am J Clin Nutr 90:862S–866S

    Article  PubMed  CAS  Google Scholar 

  • Stanley CA, Lieu YK, Hsu BY, Burlina AB, Greenberg CR, Hopwood NJ, Perlman K, Rich BH, Zammarchi E, Poncz M (1998) Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. N Engl J Med 338:1352–1357

    Article  PubMed  CAS  Google Scholar 

  • Stover PJ, Field MS (2011) Trafficking of intracellular folates. Adv Nutr 2:325–331

    Article  PubMed  CAS  Google Scholar 

  • Treberg et al (2009) On the reversibility of glutamate dehydrogenase and the source of hyperammonemia in the hyperinsulinism/hyperammonemia syndrome. Adv Enzym Regul 50:34–43

  • Treberg JR, Brosnan ME, Watford M, Brosnan JT (2010) On the reversibility of glutamate dehydrogenase and the source of hyperammonemia in the hyperinsulinism/hyperammonemia syndrome. Adv Enzyme Regul 50:34–43

    Article  PubMed  Google Scholar 

  • Wang JH, Inoue T, Higashiyama M, Guth PH, Engel E, Kaunitz JD, Akiba Y (2011) Umami receptor activation increases duodenal bicarbonate secretion via glucagon-like peptide-2 release in rats. J Pharmacol Exp Ther 339:464–473

    Article  PubMed  CAS  Google Scholar 

  • Watford M (2002) Net organ transport of l-glutamate in rats occurs via the plasma, not via erythrocytes. J Nutr 132:952–956

    PubMed  CAS  Google Scholar 

  • Windmueller HG, Spaeth AE (1975) Intestinal metabolism of glutamine and glutamate from the lumen as compared to glutamine from blood. Arch Biochem Biophys 171:662–672

    Article  PubMed  CAS  Google Scholar 

  • Windmueller HG, Spaeth AE (1980) Respiratory fuels and nitrogen metabolism in vivo in small intestine of fed rats. Quantitative importance of glutamine, glutamate, and aspartate. J Biol Chem 255:107–112

    PubMed  CAS  Google Scholar 

  • Wu G (2010) Functional amino acids in growth, reproduction and health. Adv Nutr 1:31–37

    Article  PubMed  CAS  Google Scholar 

  • Yasumatsu K, Horio N, Murata Y, Shirosaki S, Ohkuri T, Yoshida R, Ninomiya Y (2009) Multiple receptors underlie glutamate taste responses in mice. Am J Clin Nutr 90:747S–752S

    Article  PubMed  CAS  Google Scholar 

  • Yasumatsu K, Ogiwara Y, Takai S, Yoshida R, Iwatsuki K, Torii K, Margolskee RF, Ninomiya Y (2011) Umami taste in mice use multiple receptors and transduction pathways. J Physiol (E pub)

Download references

Acknowledgments

The authors’ work was supported by Canadian Institutes of Health Research.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John T. Brosnan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brosnan, J.T., Brosnan, M.E. Glutamate: a truly functional amino acid. Amino Acids 45, 413–418 (2013). https://doi.org/10.1007/s00726-012-1280-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-012-1280-4

Keywords

Navigation