Skip to main content

Glutamine Structure and Function: A Starter Pack

  • Chapter
  • First Online:
Glutamine in Clinical Nutrition

Part of the book series: Nutrition and Health ((NH))

  • 1800 Accesses

Abstract

Glutamine is a substrate central in metabolism. Its carbon skeleton can act as an anaplerotic substrate by introduction as α-oxoglutarate in the Krebs-cycle. At other sites of the cycle intermediates can branch off producing carbon chains of purines, pyrimidines, haem, proline, aspartate, non-essential amino acids, sterols, phospholipids. Its nitrogen serves in a similar manner to synthesize bases, the amino groups of non-essential amino acids and other products. A third role consists of the production of reducing equivalents essential in several functions including the maintenance of redox balance. This explains why in cell culture optimal cell proliferation only occurs when glutamine (and glucose) are added to the incubation medium.

In vivo new glutamine production is increased in trauma, inflammatory states and in conditions of growth. Peripheral (muscle) tissues yield amino acids which are used in close collaboration with the liver to produce glutamine, glycine, proline, alanine and glucose. Other amino acids derived from net protein breakdown are also released in lesser amounts. In malnourished states and in chronic inflammatory illness glutamine production has been claimed to be insufficient but studies convincingly demonstrating deficient peripheral production have not been performed. In disease states (trauma, sepsis) the maximal amount of new glutamine produced amounts to 30 g in adults. Low glutamine levels are unreliable indicators of glutamine deficiency. Very high glutamine levels have been found in patients with liver (and renal) failure and are contraindications for supplementation with glutamine.

In long term inflammatory conditions and trauma benefit has been demonstrated from glutamine supplementation, decreasing infectious complications, mortality and intestinal permeability.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Windmueller HG, Spaeth AE. Uptake and metabolism of plasma glutamine by the small intestine. J Biol Chem. 1974;249(16):5070–9.

    CAS  PubMed  Google Scholar 

  2. Watford M, Lund P, Krebs HA. Isolation and metabolic characteristics of rat and chicken enterocytes. Biochem J. 1979;178(3):589–96.

    CAS  PubMed Central  PubMed  Google Scholar 

  3. Ardawi MS. Skeletal muscle glutamine production in thermally injured rats. Clin Sci. 1988;74(2):165–72.

    CAS  PubMed  Google Scholar 

  4. Ardawi MS, Newsholme EA. Glutamine metabolism in lymphocytes of the rat. Biochem J. 1983;212(3):835–42.

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Garber AJ, Karl IE, Kipnis DM. Alanine and glutamine synthesis and release from skeletal muscle. II The precursor role of amino acids in alanine and glutamine synthesis. J Biol Chem. 1976;251(3):836–43.

    CAS  PubMed  Google Scholar 

  6. Clowes Jr GH, Hirsch E, George BC, Bigatello LM, Mazuski JE, Villee Jr CA. Survival from sepsis. The significance of altered protein metabolism regulated by proteolysis inducing factor, the circulating cleavage product of interleukin-1. Ann Surg. 1985;202(4):446–58.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Souba WW, Wilmore DW. Postoperative alteration of arteriovenous exchange of amino acids across the gastrointestinal tract. Surgery. 1983;94(2):342–50.

    CAS  PubMed  Google Scholar 

  8. Wilmore DW, Smith RJ, O’Dwyer ST, Jacobs DO, Ziegler TR, Wang XD. The gut: a central organ after surgical stress. Surgery. 1988;104(5):917–23.

    CAS  PubMed  Google Scholar 

  9. Vinnars E, Bergstom J, Furst P. Influence of the postoperative state on the intracellular free amino acids in human muscle tissue. Ann Surg. 1975;182(6):665–71.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Wischmeyer PE. Glutamine: mode of action in critical illness. Crit Care Med. 2007;35(9 Suppl):S541–4.

    Article  CAS  PubMed  Google Scholar 

  11. Bruins MJ, Deutz NE, Soeters PB. Aspects of organ protein, amino acid and glucose metabolism in a porcine model of hypermetabolic sepsis. Clin Sci (Lond). 2003;104(2):127–41.

    Article  CAS  Google Scholar 

  12. van Acker BA, Hulsewe KW, Wagenmakers AJ, von Meyenfeldt MF, Soeters PB. Response of glutamine metabolism to glutamine-supplemented parenteral nutrition. Am J Clin Nutr. 2000;72(3):790–5.

    PubMed  Google Scholar 

  13. Rennie MJ. Teasing out the truth about collagen. J Physiol. 1999;521:Pt 1:1.

    Article  Google Scholar 

  14. Bayley J-P, Devilee P. The Warburg effect in 2012. Curr Opin Oncol. 2012;24(1):62–7. doi:10.1097/CCO.1090b1013e32834deb32839e.

    Article  CAS  PubMed  Google Scholar 

  15. Oey NA, den Boer ME, Wijburg FA, et al. Long-chain fatty acid oxidation during early human development. Pediatr Res. 2005;57(6):755–9.

    Article  CAS  PubMed  Google Scholar 

  16. Pike LS, Smift AL, Croteau NJ, Ferrick DA, Wu M. Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells. Biochim Biophys Acta. 2011;1807(6):726–34.

    Article  CAS  PubMed  Google Scholar 

  17. Soeters MR, Soeters PB. The evolutionary benefit of insulin resistance. Clin Nutr. 2012;31(6):1002–7.

    Article  CAS  PubMed  Google Scholar 

  18. Ardawi MS. Glutamine and glucose metabolism in human peripheral lymphocytes. Metabolism. 1988;37(1):99–103.

    Article  CAS  PubMed  Google Scholar 

  19. Souba WW, Smith RJ, Wilmore DW. Glutamine metabolism by the intestinal tract. JPEN J Parenter Enteral Nutr. 1985;9(5):608–17.

    Article  CAS  PubMed  Google Scholar 

  20. Newsholme P. Why Is L-Glutamine Metabolism Important to Cells of the Immune System in Health, Postinjury, Surgery or Infection? J Nutr. 2001;131(9):2515S–22.

    CAS  PubMed  Google Scholar 

  21. Haussinger D, Soboll S, Meijer AJ, Gerok W, Tager JM, Sies H. Role of plasma membrane transport in hepatic glutamine metabolism. Eur J Biochem. 1985;152(3):597–603.

    Article  CAS  PubMed  Google Scholar 

  22. Olde Damink SW, de Blaauw I, Deutz NE, Soeters PB. Effects in vivo of decreased plasma and intracellular muscle glutamine concentration on whole-body and hindquarter protein kinetics in rats. Clin Sci (Lond). 1999;96(6):639–46.

    Article  CAS  Google Scholar 

  23. Hulsewe KW, van der Hulst RW, van Acker BA, von Meyenfeldt MF, Soeters PB. Inflammation rather than nutritional depletion determines glutamine concentrations and intestinal permeability. Clin Nutr. 2004;23(5):1209–16.

    Article  CAS  PubMed  Google Scholar 

  24. Oudemans-van Straaten HM, Bosman RJ, Treskes M, van der Spoel HJ, Zandstra DF. Plasma glutamine depletion and patient outcome in acute ICU admissions. Intensive Care Med. 2001;27(1):84–90.

    Article  CAS  PubMed  Google Scholar 

  25. van Acker BA, Hulsewe KW, Wagenmakers AJ, Soeters PB, von Meyenfeldt MF. Glutamine appearance rate in plasma is not increased after gastrointestinal surgery in humans. J Nutr. 2000;130(6):1566–71.

    PubMed  Google Scholar 

  26. Roth E, Zoch G, Schulz F, et al. Amino acid concentrations in plasma and skeletal muscle of patients with acute hemorrhagic necrotizing pancreatitis. Clin Chem. 1985;31:1305–9.

    CAS  PubMed  Google Scholar 

  27. Record CO, Buxton B, Chase RA, Curzon G, Murray-Lyon IM, Williams R. Plasma and Brain Amino Acids in Fulminant Hepatic Failure and their Relationship to Hepatic Encephalopathy. Eur J Clin Investig. 1976;6(1):387–94.

    Article  CAS  Google Scholar 

  28. Iber FLRH, Levenson SH, Chalmers TC. The plasma amino acids in patients with liver failure. J Lab Clin Met. 1957;50(3):417–25.

    CAS  Google Scholar 

  29. Rodas PC, Rooyackers O, Hebert C, Norberg A, Wernerman J. Glutamine and glutathione at ICU admission in relation to outcome. Clin Sci (Lond). 2012;122(12):591–7.

    Article  CAS  Google Scholar 

  30. Petersson B, Vinnars E, Waller SO, Wernerman J. Long-term changes in muscle free amino acid levels after elective abdominal surgery. Br J Surg. 1992;79(3):212–6.

    Article  CAS  PubMed  Google Scholar 

  31. Suliman ME, Qureshi AR, Stenvinkel P, et al. Inflammation contributes to low plasma amino acid concentrations in patients with chronic kidney disease. Am J Clin Nutr. 2005;82(2):342–9.

    CAS  PubMed  Google Scholar 

  32. Schmidt C, Hocherl K, Schweda F, Kurtz A, Bucher M. Regulation of renal sodium transporters during severe inflammation. J Am Soc Nephrol. 2007;18(4):1072–83.

    Article  CAS  PubMed  Google Scholar 

  33. Markossian S, Kreydiyyeh SI. TNF-alpha down-regulates the Na+-K+ATPase and the Na+-K+-2Cl-cotransporter in the rat colon via PGE2. Cytokine. 2005;30(6):319–27.

    Article  CAS  PubMed  Google Scholar 

  34. Fink MP, Delude RL. Epithelial barrier dysfunction: a unifying theme to explain the pathogenesis of multiple organ dysfunction at the cellular level. Crit Care Clin. 2005;21(2):177–96.

    Article  CAS  PubMed  Google Scholar 

  35. Clowes Jr GH, Randall HT, Cha CJ. Amino acid and energy metabolism in septic and traumatized patients. JPEN J Parenter Enteral Nutr. 1980;4(2):195–205.

    Article  PubMed  Google Scholar 

  36. Deutz NE, Reijven PL, Athanasas G, Soeters PB. Post-operative changes in hepatic, intestinal, splenic and muscle fluxes of amino acids and ammonia in pigs. Clin Sci (Lond). 1992;83(5):607–14.

    CAS  Google Scholar 

  37. Soeters PB, Grimble RF. The conditional role of inflammation in pregnancy and cancer. Clin Nutr. 2013;32(3):460–5.

    Article  CAS  PubMed  Google Scholar 

  38. Munoz-Pinedo C, El Mjiyad N, Ricci JE. Cancer metabolism: current perspectives and future directions. Cell Death Dis. 2012;3:e248.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Liu W, Le A, Hancock C, et al. Reprogramming of proline and glutamine metabolism contributes to the proliferative and metabolic responses regulated by oncogenic transcription factor c-MYC. Proc Natl Acad Sci. 2012;109(23):8983–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Son J, Lyssiotis CA, Ying H, et al. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature. 2013;496(7443):101–5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Daye D, Wellen KE. Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis. Semin Cell Dev Biol. 2012;23(4):362–9.

    Article  CAS  PubMed  Google Scholar 

  42. Van Acker BA, Hulsewe KW, Wagenmakers AJ, et al. Absence of glutamine isotopic steady state: implications for the assessment of whole-body glutamine production rate. Clin Sci (Lond). 1998;95(3):339–46.

    Article  Google Scholar 

  43. Carbonnel F, Messing B, Darmaun D, et al. Energy and protein metabolism in malnutrition due to nonneoplastic gastrointestinal diseases. Metabolism. 1995;44(9):1110–5.

    Article  CAS  PubMed  Google Scholar 

  44. Yarasheski KE, Zachwieja JJ, Gischler J, Crowley J, Horgan MM, Powderly WG. Increased plasma gln and Leu Ra and inappropriately low muscle protein synthesis rate in AIDS wasting. Am J Physiol. 1998;275(4 Pt 1):E577–83.

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Stumvoll M, Perriello G, Nurjhan N, et al. Glutamine and alanine metabolism in NIDDM. Diabetes. 1996;45(7):863–8.

    Article  PubMed  Google Scholar 

  46. Jackson NC, Carroll PV, Russell-Jones DL, Sonksen PH, Treacher DF, Umpleby AM. The metabolic consequences of critical illness: acute effects on glutamine and protein metabolism. Am J Physiol. 1999;276(1 Pt 1):E163–70.

    CAS  PubMed  Google Scholar 

  47. Darmaun D, Messing B, Just B, Rongier M, Desjeux JF. Glutamine metabolism after small intestinal resection in humans. Metabolism. 1991;40(1):42–4.

    Article  CAS  PubMed  Google Scholar 

  48. Gore DC, Jahoor F. Glutamine kinetics in burn patients. Comparison with hormonally induced stress in volunteers. Arch Surg. 1994;129(12):1318–23.

    Article  CAS  PubMed  Google Scholar 

  49. Goeters C, Wenn A, Mertes N, et al. Parenteral L-alanyl-L-glutamine improves 6-month outcome in critically ill patients. Crit Care Med. 2002;30(9):2032–7.

    Article  CAS  PubMed  Google Scholar 

  50. Dechelotte P, Hasselmann M, Cynober L, et al. L-alanyl-L-glutamine dipeptide-supplemented total parenteral nutrition reduces infectious complications and glucose intolerance in critically ill patients: the French controlled, randomized, double-blind, multicenter study. Crit Care Med. 2006;34(3):598–604.

    Article  CAS  PubMed  Google Scholar 

  51. Grau T, Bonet A, Minambres E, et al. The effect of L-alanyl-L-glutamine dipeptide supplemented total parenteral nutrition on infectious morbidity and insulin sensitivity in critically ill patients. Crit Care Med. 2011;39(6):1263–8.

    Article  CAS  PubMed  Google Scholar 

  52. Heyland D, Muscedere J, Wischmeyer PE, et al. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013;368(16):1489–97.

    Article  CAS  PubMed  Google Scholar 

  53. Brusilow SW, Cooper AJ. Encephalopathy in acute liver failure resulting from acetaminophen intoxication: new observations with potential therapy. Crit Care Med. 2011;39(11):2550–3.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Hulsewe KW, van Acker BA, Hameeteman W, et al. Does glutamine-enriched parenteral nutrition really affect intestinal morphology and gut permeability? Clin Nutr. 2004;23(5):1217–25.

    Article  CAS  PubMed  Google Scholar 

  55. Fong YM, Tracey KJ, Hesse DG, Albert JD, Barie PS, Lowry SF. Influence of enterectomy on peripheral tissue glutamine efflux in critically ill patients. Surgery. 1990;107(3):321–6.

    CAS  PubMed  Google Scholar 

  56. Vesali RF, Klaude M, Rooyackers OE, TJader I, Barle H, Wernerman J. Longitudinal pattern of glutamine/glutamate balance across the leg in long-stay intensive care unit patients. Clin Nutr. 2002;21(6):505–14.

    Article  CAS  PubMed  Google Scholar 

  57. Gore D, Wolf S, Herndon D, Wolfe R. Relative influence of glucose and insulin on peripheral amino acid metabolism in severely burned patients. J Parenter Enter Nutr. 2002;26(5):271–7.

    Article  CAS  Google Scholar 

  58. Carli F, Webster J, Ramachandra V, et al. Aspects of protein metabolism after elective surgery in patients receiving constant nutritional support. Clin Sci (Lond). 1990;78(6):621–8.

    CAS  Google Scholar 

  59. Mjaaland M, Unneberg K, Larsson J, Nilsson L, Revhaug A. Growth hormone after abdominal surgery attenuated forearm glutamine, alanine, 3-methylhistidine, and total amino acid efflux in patients receiving total parenteral nutrition. Ann Surg. 1993;217(4):413–22.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter B. Soeters M.D., Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Soeters, P.B. (2015). Glutamine Structure and Function: A Starter Pack. In: Rajendram, R., Preedy, V., Patel, V. (eds) Glutamine in Clinical Nutrition. Nutrition and Health. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1932-1_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1932-1_1

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1931-4

  • Online ISBN: 978-1-4939-1932-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics