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Glutamine metabolism in the gastrointestinal tract of the rat assessed by the relative activities of glutaminase (EC 3.5.1.2) and glutamine synthetase (EC 6.3.1.2)

Published online by Cambridge University Press:  09 March 2007

L. A. James ,
P. G. Lunn  and
M. Elia
L. A. James
Affiliation:
MRC Dunn Nutrition Centre, Downham's Lane, Milton Road, Cambridge CB4 1XJ, UK
P. G. Lunn*
Affiliation:
MRC Dunn Nutrition Centre, Downham's Lane, Milton Road, Cambridge CB4 1XJ, UK
M. Elia
Affiliation:
MRC Dunn Nutrition Centre, Downham's Lane, Milton Road, Cambridge CB4 1XJ, UK
*
*Corresponding author:Dr Peter Lunn, fax + 44 (0) 1223 426617, email Peter.Lunn@mrc-dunn.cam.ac.uk
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Abstract

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The activities of the two key enzymes involved in glutamine metabolism, glutaminase (EC 3.5.1.2) and glutamine synthetase (EC 6.3.1.2), have been measured in the various tissues of the gastrointestinal (GI) tract of the rat, from the mouth to the rectum. Glutaminase activity was particularly high in the mucosa of the small intestine, where its activity accounted for more than 80% of the total activity of the GI tract. In contrast, the mouth and oesophagus had very low activities, accounting for less than 2% of the total. Glutamine synthetase was mainly confined to the lower part of the stomach, which accounted for almost 90% of the total activity of the GI tract. Activity in the small intestine was very low, accounting for less than 2% of the total, and similarly low levels were found in the mouth and oesophagus. The data provide the most complete information on the distribution of these enzymes in the GI tract of the rat and suggest: (a) that the mucosa of the small intestine has the highest capacity for glutamine breakdown but the lowest capacity for its synthesis, and so requires an external source of this amino acid; (b) that there is little potential for glutamine synthesis or breakdown in the mouth and oesophagus; and (c) that the lower stomach has a substantial capacity to synthesize glutamine, in contrast to the rest of the GI tract. The results of the investigation are relevant to sites of glutamine metabolism in therapeutic studies involving glutamine administration discussed with reference to reports of the effects of glutamine administration on GI tract injury.

Keywords

Gastrointestinal tractGlutaminaseGlutamine synthetaseRat
Type
General Nutrition
Information
British Journal of Nutrition , Volume 79 , Issue 4 , April 1998 , pp. 365 - 372
Copyright
Copyright © The Nutrition Society 1998

References

Anderson, NG & Hanson, PJ (1983) Arteriovenous differences for amino acids across control and acid-secreting rat stomach in vivo. Biochemical Journal 210, 451–455.CrossRefGoogle ScholarPubMed
Ardawi, MSM (1987 a) The maximal activity of phosphate-dependent glutaminase and glutamine metabolism in late-pregnant and peak-lactating rats. Biochemical Journal 242, 75–80.CrossRefGoogle ScholarPubMed
Ardawi, MSM (1987 b) Maximal activities of glutaminase and some enzymes of glycolysis and ketone body utilization and rates of utilization of glutamine, glucose and ketone bodies by intestinal mucosa after burn injury. Burns 13, 438–444.CrossRefGoogle ScholarPubMed
Ardawi, MSM (1988 a) Skeletal muscle glutamine production in thermally injured rats. Clinical Science 74, 165–172.CrossRefGoogle ScholarPubMed
Ardawi, MSM (1988 b) Glutamine and ketone-body metabolism in the gut of streptozotocin diabetic rats. Biochemical Journal 249, 565–572.CrossRefGoogle ScholarPubMed
Ardawi, MSM (1991). Glutamine in the lungs of glucocorticoidtreated rats. Clinical Science 81, 37–42.CrossRefGoogle ScholarPubMed
Ardawi, MSM & Jamal, YS (1990) Glutamine metabolism in skeletal muscle of glucocorticoid-treated rats. Clinical Science 79, 139–147.CrossRefGoogle ScholarPubMed
Ardawi, MSM, Majzoub, MF, Kateilah, SM & Newsholme, EA (1991) Maximal activity of phosphate-dependent glutaminase and glutamine metabolism in septic rats. Journal of Laboratory and Clinical Medicine 118, 26–32.Google ScholarPubMed
Ardawi, MSM, Majzoub, MF & Newsholme, EA (1988) Effect of glucocorticoid treatment on glucose and glutamine metabolism by the small intestine of the rat. Clinical Science 75, 93–100.CrossRefGoogle Scholar
Arola, LI, Palou, A, Remesar, X & Alemany, M (1981 a) Glutamine synthetase activity in the organs of fed and 24 hour fasted rats. Hormone and Metabolic Research 13, 199–202.CrossRefGoogle Scholar
Arola, LI, Palou, A, Remesar, X & Alemany, M (1981 b) Changes in glutamine synthetase activity in the different organs of developing rats. Archives Internationales de Physiologie et de Biochimie 89, 189–194.Google ScholarPubMed
Budohoski, L, Challis, RAI & Newsholme, EA (1982) Effects of starvation on the maximal activities of some glycolytic and citric-acid enzymes and glutaminase in mucosa of the small intestine of the rat. Biochemical Journal 206, 169–172.CrossRefGoogle ScholarPubMed
Elia, M (1991) The inter-organ flux of substrates in fed and fasted man as indicated by arterio–venous balance studies. Nutrition Research Reviews 4, 3–31.CrossRefGoogle Scholar
Elia, M (1992) Glutamine in parenteral nutrition. International Journal of Food Sciences and Nutrition 43, 47–59.CrossRefGoogle Scholar
Elia, M (1996) Nutrition of the gastrointestinal tract. In Recent Developments in Infant Nutrition, 10th Nutricia Symposium, pp. 318–348 [GoedhartJG Bindels, AC JG Bindels, AC, Visser, HKA, editors]. Dordrecht, Boston and London: Kluwer Academic Publishers.CrossRefGoogle Scholar
Fox, AD, Kripke, SA, Berman, JM, McGintey, RM, Settle, RG & Rombeau, JL (1988) Dexamethasone administration induces increased glutaminase specific activity in the jejunum and colon. Journal of Surgical Research 44, 391–396.CrossRefGoogle ScholarPubMed
Girard, G & Butterworth, RF (1992) Effect of portocaval anastomosis on glutamine synthetase activities in liver, brain and skeletal muscle. Digestive Diseases and Sciences 37, 1121–1126.CrossRefGoogle Scholar
Hahn, P, Taller, M & Chan, H (1988) Pyruvate carboxylase, phosphate-dependent glutaminase and glutamate dehydrogenase in the developing rat small intestinal mucosa. Biology of the Neonate 53, 362–366.CrossRefGoogle ScholarPubMed
Hortelano, P, Garcia-Salgervo, L, Alleyne, GAO & Lupianez, JA (1991 a) Comparative effects of plasma from acutely acidotic rats on the activity of phosphate-dependent glutaminases from several animal tissues. Chemosphere 22, 521–528.Google Scholar
Hortelano, P, Garcia-Salgervo, L, Alleyne, GAO & Lupianez, JA (1991 b) Variations in the kinetic response of several different phosphate-dependent glutaminase isoenzymes during acute metabolic acidosis. Molecular and Cellular Biochemistry 108, 113–123.CrossRefGoogle ScholarPubMed
Houdijk, APJ, van Leeuwen, PAM, Boermeester, MA, van Lambalgen, T, Teerlink, T, Flinkerbusch, EL, Sauerwein, HP & Wesdorp, RIC (1994) Glutamine-enriched enteral diet increases splanchnic blood flow in the rat. American Journal of Physiology 267, G1035–G1040.Google ScholarPubMed
Jebb, SA, Marcus, R, Wetherall, A & Elia, M (1995) A pilot study of oral glutamine supplementation in patients receiving bone marrow transplants. Clinical Nutrition 14, 162–165.CrossRefGoogle ScholarPubMed
Jebb, SA, Osborne, RJ, Maughan, TS, Mohideen, N, Mack, P, Mart, D, Shelleg, MD & Elia, M (1994) 5-Fluorouracil and folinic acid induced mucositis: no effect of oral glutamine supplementation. British Journal of Cancer 70, 732–735.Google ScholarPubMed
Jennings, G & Elia, M (1996) Changes in protein distribution in normal and protein deficient rats during an acute-phase injury response. British Journal of Nutrition 76, 123–132.CrossRefGoogle ScholarPubMed
King, PA, Goldstein, L & Newsholme, EA (1983) Glutamine synthetase activity of muscle in acidosis. Biochemical Journal 216, 523–525.CrossRefGoogle ScholarPubMed
Klimberg, VS, Souba, WW, Dolson, DJ, Salloum, RM, Hautamaki, DA, Plumley, WM, Mendenhall, WM, Bova, FJ, Khan, SR, Hackett, RL, Bland, KJ & Copeland, EM (1990). Prophylactic glutamine protects the intestinal mucosa from radiation injury. Cancer 66, 62–68.3.0.CO;2-E>CrossRefGoogle ScholarPubMed
Krebs, HA (1980) Glutamine metabolism in the animal body. In Glutamine: Metabolism, Enzymology and Regulation, pp. 319–329 [Mora, J and Palacios, R, editors]. New York: Academic Press.CrossRefGoogle Scholar
Lacey, JM & Wilmore, DW (1990) Is glutamine a conditionally essential amino acid? Nutrition Reviews 48, 297–309.CrossRefGoogle ScholarPubMed
Lund, PA (1970) Radiochemical assay for glutamine synthetase and activity of the enzyme in rat tissues. Biochemical Journal 118, 35–39.CrossRefGoogle ScholarPubMed
Lund, PA (1974) l-Glutamine determination with glutaminase and glutamate dehydrogenase. In Methods of Enzymatic Analysis, Vol. 4, pp. 1719–1722 [Bergmeyer, HU, editor]. New York: Academic Press.Google Scholar
Neilly, PJD, Gardiner, KR, Kirk, SJ, Jennings, G, Anderson, NH & Elia, M (1995) Endotoxaemia and cytokine production in experimental inflammatory bowel disease. British Journal of Surgery 83, 1479–1482.Google Scholar
O'Dwyer, ST, Smith, RJ, Hwang, TL & Wilmore, DW (1989) Maintenance of small bowel mucosa with glutamine enriched parenteral nutrition. Journal of Parenteral and Enteral Nutrition 13, 579–585.CrossRefGoogle ScholarPubMed
Okabe, S, Honda, K, Takeuchi, K & Takagi, T (1975) Inhibitory effect of l-glutamine on gastric irritation and back diffusion of gastric acid in response to aspirin in the rat. Digestive Diseases and Sciences 20, 626–631.CrossRefGoogle ScholarPubMed
Pinkus, LM & Windmueller, HG (1977) Phosphate-dependent glutaminase of the small intestine: localisation and role in intestinal glutamine metabolism. Archives of Biochemistry and Biophysics 182, 506–517.CrossRefGoogle ScholarPubMed
Poynton, CH, Maughan, TS, Jebb, SA & Elia, M (1995) Glycyl L-glutamine reduces gut toxicity in bone marrow transplantation. Blood 86, Suppl. 1, 2258.Google Scholar
Remesar, X, Arola, LI & Alemany, M (1982) Glutamine synthetase activities in rat tissues during pregnancy and lactation. Hormone and Metabolic Research 14, 419–421.CrossRefGoogle ScholarPubMed
Remesar, X, Arola, LI, Palou, A & Alemany, M (1985) Activities of amino acid metabolising enzymes in the stomach and small intestine of developing rats. Reproduction, Nutrition, Development 25, 861–866.CrossRefGoogle Scholar
Salloum, RM, Copeland, EM & Souba, WW (1991) Brush border transport of glutamine and other substrates during sepsis and endotoxemia. Annals of Surgery 213, 401–410.CrossRefGoogle ScholarPubMed
Schloerb, PR & Amare, M (1991) Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications. Journal of Parenteral and Enteral Nutrition 15, 407–413.Google Scholar
Shive, W, Snider, RN, DuBilier, B, Rude, JD, Clarke, GE & Ravel, JO (1957) Glutamine treatment of peptic ulcer. Texas State Journal of Medicine, November issue, 840-843.Google Scholar
Souba, WW, Herskowitz, K, Austgen, TR, Chen, MK & Salloum, RM (1990) Glutamine nutrition: theoretical considerations and therapeutic impact. Journal of Parenteral and Enteral Nutrition 14, Suppl., 237S–243S.CrossRefGoogle ScholarPubMed
Watford, M, Smith, EM & Erbelding, EJ (1984) The regulation of phosphate-activated glutaminase activity and glutamine metabolism in the streptozotocin-diabetic rat. Biochemical Journal 224, 207–214.CrossRefGoogle ScholarPubMed
Windmueller, HG (1982) Glutamine utilization by the small intestine. In Advances in Enzymology, Vol. 53, pp. 201–237 [Meister, A, editor]. New York: John Wiley.Google Scholar
Windmueller, HG & Spaethe, AE (1975) Intestinal metabolism of glutamine and glutamate from the lumen as compared to glutamine from the blood. Archives of Biochemistry and Biophysics 171, 662–672.CrossRefGoogle Scholar
Wischemeyer, P, Pemberton, JH & Phillips, SF (1993) Chronic pouchitis after ileal pouch anastomosis: responses to butyrate and glutamine suppositories in a pilot study. Mayo Clinic Proceedings 68, 978–981.CrossRefGoogle Scholar
Wusteman, M, Tate, H, Weaver, L, Austin, S, Neale, G & Elia, M (1995) The effect of enteral glutamine deprivation and supplementation on the structure of rat small intestinal mucosa during a !systemic" injury response. Journal of Parenteral and Enteral Nutrition 19, 22–27.Google ScholarPubMed
Yoshida, S, Leskiw, MJ, Schluter, MD, Bush, KT, Nagele, RG, Lanza-Jacoby, S & Stein, JP (1992) Effect of total parenteral nutrition, systemic sepsis and glutamine on gut mucosa in rats. American Journal of Physiology 263, E368–E373.Google ScholarPubMed
Ziegler, TR, Young, LS, Benfell, K, Scheltinga, M, Horlos, K, Bye, R, Morrow, FD, Jacobs, DO, Smith, RJ, Antin, JH & Wilmore, DW (1992) Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone-marrow transplantation. Annals of Internal Medicine 116, 821–828.CrossRefGoogle ScholarPubMed