Hostname: page-component-cd9895bd7-dzt6s Total loading time: 0 Render date: 2024-12-28T04:01:23.272Z Has data issue: false hasContentIssue false

Metabolism of ornithine, α-ketoglutarate and arginine in isolated perfused rat liver

Published online by Cambridge University Press:  09 March 2007

Jean Pascal De Bandt
Affiliation:
Laboratoire de Biochimie A, Paris, France
Luc Cynober
Affiliation:
Laboratoire de Biochimie A, Paris, France INSERM U 402 Hôpital Saint Antoine, Paris, France
Soo Kyung Lim
Affiliation:
Laboratoire de Biochimie A, Paris, France
Colette Coudray-Lucas
Affiliation:
Laboratoire de Biochimie A, Paris, France INSERM U 402 Hôpital Saint Antoine, Paris, France
Raoul Poupon
Affiliation:
INSERM U 402 Hôpital Saint Antoine, Paris, France
Jacqueline Giboudeau
Affiliation:
Laboratoire de Biochimie A, Paris, France
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Ornithine (Orn; α-ketoglutarate (αKG) salt) and arginine (Arg) supplementation of enteral diets has been advocated in the treatment of hypercatabolism of trauma patients, but both compounds are subject to extensive hepatic metabolism. To compare the metabolism of these two compounds and to evaluate the possible influence of the αKG moiety, livers were perfused with αKG, Orn, ornithine α-ketoglutarate (OKG) or Arg (n 6 in each group) for 1 h. Arg uptake was nearly fourfold higher than Orn uptake (690 (SD 162) ν. 178 (SD 30) nmol/min per g liver), and Orn uptake was not modified by αKG. Orn was totally metabolized by the liver, whereas Arg led to Orn release (408 (SD 159) nmol/min per g liver) and a threefold stimulation of urea production (Arg 1·44 (SD 0·22) ν. Orn 0·45 (SD 0.09) μol/min per g liver). αKG alone only increased hepatic aspartate uptake but, when associated with Orn as OKG, it led to an increase in giutamate release and in proiine content in the liver and to a decrease in proiine uptake. From these findings we conclude that (1) Arg load is extensively metabolized by the liver, inducing urea production, (2) in enteral use, Orn supplementation appears preferable to Arg as it is less ureogenic (as also recently demonstrated in vivo in stressed rats receiving isomolar amounts of Arg and Orn), (3) the liver participates in the Orn-αKG metabolic interaction, mostly in proiine metabolism, which occurs in the splanchnic area.

Type
Hepatic metabolism in rats
Copyright
Copyright © The Nutrition Society 1995

References

REFERENCES

Barbul, A. (1986). Arginine: biochemistry, physiology and therapeutic implications. Journal of Parenteral and Enteral Nutrition 10, 227238.Google Scholar
Barbul, A. (1990). Arginine and immune function. Nutrition 10, 5358.Google Scholar
Beliveau-Carey, G., Cheung, C. W., Cohen, N. S., Brusilow, S. & Raijman, L. (1993). Regulation of urea and citrulline synthesis under physiological conditions. Biochemical Journal 292, 241247.Google Scholar
Blachier, F., Darcy-Vrillon, B., Sener, A, Dué, P. H. & Malaisse, W. H. (1991). Arginine metabolism in rat enterocytes. Biochimica et Biophysica Acta 1092, 304310.Google Scholar
Burlina, A. (1985). 2-Oxoglutarate. In Methods of Enzymatic Analysis, 3rd ed., Vol. 7, pp. 2024 [Bergmeyer, H. U. editor]. Weinheim: Verlag Chemie.Google Scholar
Cynober, L. (1991). Ornithine α-ketoglutarate in nutritional support. Nutrition 7, 313322.Google Scholar
Cynober, L. (1994). Can arginine and ornithine support gut functions? Gut 35, Suppl. 1, S42S45.Google Scholar
Cynober, L., Coudray-Lucas, C., De Bandt, J. P., Guechot, J., Aussel, C., Salvucci, M. & Giboudeau, J. (1990). Action of ornithine alpha-ketoglutarate, ornithine hydrochloride and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects. Journal of the American College of Nutrition 9, 212.Google Scholar
Daly, J. M., Reynolds, J., Thom, A., Kinsley, L., Dietrick-Gallagher, M., Shou, J. & Ruggieri, B. (1988). Immune and metabolic effects of arginine in the surgical patient. Annals of Surgery 208, 512523.Google Scholar
Dhanakoti, S. N., Brosnan, J. T., Herzberg, G. R. & Brosnan, M. E. (1990). Renal arginine synthesis: studies in vitro and in vivo. American Journal of Physiology 259, E437JM2.Google Scholar
De Bandt, J. P., Cynober, L., Ballet, F., Coudray-Lucas, C., Rey, C. & Giboudeau, J. (1990). Amino acid metabolism in isolated perfused rat liver. Journal of Surgical Research 49, 813.Google Scholar
De Bandt, J. P., Cynober, L., Ballet, F., Rey, C., Coudray-Lucas, C. & Giboudeau, J. (1991). Effects of norepinephrine on hepatic amino acid metabolism in isolated perfused rat liver. Nutrition 6, 363366.Google Scholar
Grillo, M. A. (1985). Metabolism and function of polyamines. International Journal of Biochemistry 17, 943948.Google Scholar
Hammarqvist, F., Wernerman, J. & Vinnars, E. (1990). Effects of an amino acid solution enriched with either branched chain amino acids or ornithine α-ketoglutarate on the postoperative intracellular amino acid concentration of skeletal muscle. British Journal of Surgery 77, 214218.Google Scholar
Haussinger, D. (1989). Glutamine metabolism in the liver: overview and current concepts. Metabolism 38, 1417.Google Scholar
Le Boucher, J., Coudray-Lucas, C., Lasnier, E., Jardel, A., Ekindjian, O. G. & Cynober, L. (1992). Actions Comparées de 1'alpha-cétoglutarate d'ornithine (ACO) et de l'alpha-cétoglutarate d'arginine (ACA) chez le rat Brûlé (A comparison of the effects of ornithine α-ketoglutarate (ACO) and arginine α-ketoglutarate (ACA) in burned rats). Nutrition Clinique et Métabolisme 6, Suppl., 17 abstr.Google Scholar
Lescoat, G., Theze, N., Fraslin, J. M., Pasdeloup, N., Kneip, B. & Guguen-Guillouzo, C. (1987). Influence of ornithine on albumin synthesis by fetal and neonatal hepatocytes maintained in culture. Cellular Differentiation 21, 2129.Google Scholar
Lund, P. & Wiggins, D. (1986). The ornithine requirement of urea synthesis. Biochemical Journal 239, 773776.Google Scholar
Medina, M. A., Urdiales, J. L., Nunez de Castro, I. & Sanchez-Jimenez, F. (1991). Diamines interfere with the transport of L-ornithine in Ehrlich-cell plasma-membrane vesicles. Biochemical Journal 280, 825827.Google Scholar
Meijer, A. J., Lamers, W. H. & Chamuleau, R. A. F. M. (1990). Nitrogen metabolism and ornithine cycle function. Physiological Review 70, 701748.Google Scholar
Metoki, K. & Hommes, F. A. (1984). The uptake of ornithine and lysine by isolated hepatocytes and fibroblasts. International Journal of Biochemistry 16, 833836.Google Scholar
Molimard, R., Morin, R. & Eskenasy, P. (1968). Etude pharmacologique de l'alpha-cétoglutarate de L (+) ornithine (A pharmacological study of L (+) ornithine α-ketoglutarate). Problémes de Réanimation 5, 869881.Google Scholar
Morimoto, B. H., Brady, J. F. & Atkinson, D. E. (1990). Effect of level of dietary protein on arginine-stimulated citrulline synthesis. Biochemical Journal 272, 671675.Google Scholar
Moseley, R. H. (1993). Hepatic uptake of amino acids. In Hepatic Transport and Bile Secretion: Physiology and Pathophysiology, pp. 337349 [Tavoloni, N. and Berk, P. D., editors]. New York: Raven Press Ltd.Google Scholar
Rennie, M. J., Babij, P., Taylor, P. M., Hundal, H. S., MacLennan, P., Watt, P. W., Jepson, M. M. & Millward, D. J. (1986). Characteristics of a glutamine carrier in skeletal muscle have important consequences for nitrogen loss in injury, infection and chronic disease. Lancet ii, 10081012.Google Scholar
Rérat, A., Jung, J. & Kandé, J. (1988). Absorption kinetics of dietary hydrolysis products in conscious pigs given diets with different amounts of fish protein. British Journal of Nutrition 60, 105120.Google Scholar
Saheki, T., Tsuda, M., Tanaka, T. & Katunuma, N. (1975). Analysis of regulatory factors for urea synthesis by isolated perfused rat liver. Journal of Biochemistry 77, 671678.Google Scholar
Saito, H., Trocki, O., Wang, S. L., Gonce, S. J., Joffe, S. N. & Alexander, J. W. (1987). Metabolic and immune effects of dietary arginine supplementation after bum. Archives of Surgery 122, 784789.Google Scholar
Tizianello, A., De Ferrari, G., Garibotto, G., Gurreri, G. & Robando, C. (1980). Renal metabolism of amino acids and ammonia in subjects with normal renal function and in patients with chronic renal insufficiency. Journal of Clinical Investigation 65, 11621173.Google Scholar
Vaubourdolle, M., Jardel, A., Coudray-Lucas, C., Ekindjian, O. G., Agneray, J. & Cynober, L. (1988). Metabolism and kinetics of parenterally administered ornithine and alpha-ketoglutarate in healthy and burned animals. Clinical Nutrition 7, 105111.Google Scholar
Vaubourdolle, M., Jardel, A., Coudray-Lucas, C., Ekindjian, O. G., Agneray, J. & Cynober, L. (1989). Fate of enterally administered ornithine in healthy animals: interactions with alpha-ketoglutarate. Nutrition 5, 183197.Google Scholar
Vaubourdolle, M., Salvucci, M., Coudray-Lucas, C., Agneray, J., Cynober, L. & Ekindjian, O. G. (1990). Action of ornithine alpha-ketoglutarate on DNA synthesis by human fibroblasts. In Vitro Cellular and Developmental Biology 26, 187192.Google Scholar
Welbourne, T. C. (1993). Alpha ketoglutarate, ornithine and growth hormone displace glutamine dependent ammoniagenesis and enhance renal base generation and function. Clinical Nutrition 12, 4950.Google Scholar
Wernerman, J., Hammarqvist, F. & Vinnars, E. (1990). Alpha-ketoglutarate and postoperative muscle catabolism. Lancet 335, 701703.Google Scholar
White, M. F. & Christensen, H. N. (1982). Cationic amino acid transport into cultured animal cells. Journal of Biological Chemistry 257, 44504457.Google Scholar
Windmueller, H. G. & Spaeth, A. E. (1976). Metabolism of absorbed aspartate, asparagine and arginine by rat small inestine. in vivo Archives of Biochemistry and Biophysics 175, 660676.Google Scholar
Windmueller, H. G. & Spaeth, A. E. (1981). Source and fate of circulating citrulline. American Journal of Physiology 241, E473E480.Google Scholar
Winkler, S., Hölzenbein, T., Karner, J. & Roth, E. (1993). Kinetics of organ specific metabolism of a bolus injection into the jejunum of glutamine, α-ketoglutarate, ornithine and ornithine α-ketoglutarate. Clinical Nutrition 12, 5657.Google Scholar
Ziegler, F., Coudray-Lucas, C., Jardel, A., Lasnier, E., Le Boucher, J., Ekindjian, O. G. & Cynober, L. (1992). Ornithine α-ketoglutarate and glutamine supplementation during refeeding of food-deprived rats. Journal of Parenteral and Enteral Nutrition 16, 505510.Google Scholar