The metabolic effects of intravenous peptides have undergone extensive investigation in recent years. Dipeptide solutions provide a mechanism for the provision of selected amino acids that may be conditionally indispensable under certain clinical conditions. In particular, amino acids such as cystine, glutamine, and tyrosine may be difficult to provide in their free form, but their availability can be increased substantially when they are supplied in the form of a dipeptide. Animal and human studies have demonstrated that parenteral dipeptides are cleared rapidly from the plasma compartment and favorably influence nitrogen equilibrium in healthy volunteers and catabolic patients. Certain dipeptides offer the potential for tailoring tissue-specific nutrition therapy. It seems likely that parenteral peptides will offer a major change in the delivery of intravenous nutrients.
Get full access to this article
View all access options for this article.
References
1.
Cuthbertson DPParenteral and enteral nutrition: whither the future. Clin Nutr1982;1:5-23.
2.
Abelson J.Revolution in biology. Science1980 ;209:1317-20.
3.
Wilmore DWThe practice of clinical nutrition: how to prepare for the future . JPEN1989;13:337-43.
4.
Fürst P.Criteria underlying the formulation of amino acid regimens: established and new approaches. In: Kleinberger G, Deutsch E, eds. New aspects of clinical nutrition . Basel: Karger, 1983:361-76.
5.
Brennan MF, Cerra F., Daly JM, et al. Report of a research workshop: branched-chain amino acids in stress and injury. JPEN1986;10:446-52.
6.
Fürst P.Peptides in clinical nutrition. Clin Nutr1985;4(suppl): 105-5.
7.
Adibi SAExperimental basis for use ofpeptides as substrates for parenteral nutrition: a review. Metabolism1987;36:1001-11.
8.
Adibi SA, Fekl W., Fürst P., et al. Dipeptides as new substrates in clinical nutrition therapy. Basel: Karger, 1987
9.
Fürst P.Peptides in clinical nutrition. Clin Nutr1991;10(suppl 1):19-24.
10.
Silk DBA.Intestinal absorption of nutrients. In: Fischer JE, ed. Surgical nutrition . Boston: Little, Brown and Company , 1983: 19-64.
11.
Matthews DMIntroduction. In: Adibi SA, Fekl W, Fürst P, et al, eds. Dipeptides as new substrates in nutrition therapy. Basel: Karger, 1987:1-5.
12.
Laidlaw SA, Kopple JDNewer concepts of the indispensable amino acids. Am J Clin Nutr1987;46:593-605.
13.
Gaull G., Sturman JA, Räihä NCR.Development of mammalian sulfur metabolism: absence of cystathionase in human fetal tissues. Pediatr Res1972;6:538-47.
14.
Chawla RK, Lewis FW, Kutner M., et al. Plasma cysteine, cystine, and glutathione in cirrhosis. Gastroenterology1984;87:770-6.
15.
Fürst P.Intracellular muscle free amino acids-their measurement and function . Proc Nutr Soc1983;42:451-62.
16.
Souba WWGlutamine: a key substrate for the splanchnic bed. Annu Rev Nutr1991;11:285-308.
17.
Souba WW, Klimberg VS, Plumley DA, et al. The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection. J Surg Res1990;48:383-91.
18.
Alvestrand A., Ahlberg M., Bergström J., et al. Clinical results of long term treatment with a low protein diet and a new amino acid preparation in patients with chronic uremia. Clin Nephrol1983;19:67-73.
19.
Snyderman SERecommendations for parenteral amino acid requirements. In: Winters RW, Hasselmeyer EG , eds. Intravenous nutrition in the high risk infant. New York: John Wiley, 1975;422-3.
20.
Rudman D., Kutner M., Ansley J., et al. Hypotyrosinemia, hypoystinemia and failure to retain nitrogen during total parenteral nutrition of cirrhotic patients. Gastroenterology1981;81:1025-35.
21.
Böhler S., Neuhäuser-Berthold M., Wagner K., et al. Cystein in der parenteralen Ernährung: Vergleichende Studien über N-Acetylcystein und N,N-Diacetylcystin am Modell der Ratte. Infusionsther Klin Ern1988;15:89-92.
22.
Meister A.Metabolism of glutamine. Physiol Rev1956;36: 103-27.
23.
Stehle P., Kiihne B., Kubin W., et al. Synthesis and characterization of tyrosine- and glutamine-containing peptides. J Appl Biochem1982;4:280-6.
24.
Stehle P., Fürst P.Isotachophoretic control of peptide synthesis and purification. A novel approach using ultraviolet detection at 206 nm. J Chromatogr1985;346:271-9.
25.
Stehle P.Bedarfsgerechte Bereitstellung von kurzkettigen Peptiden-Eine Voraussetzung für deren Einsatz in der künstlichen Ernährung. Infusionsther Klin Ern1988;15:27-32.
26.
Stehle P., Pfaender P., Fürst P.Isotachophoretic analysis of a synthetic dipeptide L-alanyl-L-glutamine. Evidence for stability during heat sterilization. J Chromatogr1984;294:507-12.
27.
Jakubke H-D. , Kuhl P., Könnecke A.Grundprinzipien der proteasekatalysierten Knüpfung der Peptidbindung. Angew Chem1985 ;97:79-87.
28.
Groeger U., Stehle P., Fürst P., et al. Papain-catalyzed synthesis of dipeptides. Food Biotechnol1989;2:187-98.
29.
Stehle P., Bahsitta H-P., Monter B., et al. Papain-catalyzed synthesis of dipeptides. A novel approach using free amino acids as nucleophiles. Enzyme Microb Technol1990;12:56-60.
30.
Monter B., Herzog B., Stehle P., et al. Kinetically controlled synthesis of dipeptides using ficin as biocatalyst. Biotechnol Appl Biochem1991;14:183-191.
31.
Daabees TT, Stegink LDL-Alanyl-L-tyrosine as a tyrosine source during intravenous nutrition of the rat. J Nutr1978;108:1104-13.
32.
Krzysik BA, Adibi SAComparison of metabolism of glycine injected intravenously in free and dipeptide forms. Metabolism1979;28:1211-7.
33.
Adibi SA, Morse ELEnrichment of glycine pool in plasma and tissues by glycine, di-, tri-, and tetraglycine. Am J Physiol1982;243:E413-7.
34.
Amberger I. , Fürst P., Godel H., et al. The potential parenteral application of the peptide L-alanyl-L-glutamine as a nitrogen source in severe catabolic states. Hoppe-Seyler's Z Physiol Chem1983 ;364:1253-4.
35.
Stehle P., Ratz I., Fürst P.In vivo utilization of intravenously supplied L-alanyl-L-glutamine in various tissues of the rat. Nutrition1989 ;5:411-5.
36.
Stehle P., Ratz I., Fürst P.Whole-body autoradiography in the rat after intravenous bolus injection of L-alanyl-L-[U-14C]glutamine. Ann Nutr Metab1991;35:213-20.
37.
Stehle P., Albers S., Pollack L., et al. In vivo utilization of cystine-containing synthetic short chain peptides after intravenous bolus injection in the rat. J Nutr1988;118:1470-4.
38.
Hilton M., Hilton F., Montgomery W., et al. Use of the stable peptide, gamma-L-glutamyl-L-tyrosine, as an intravenous source of tyrosine in mice. Metabolism1991;40:634-8.
39.
Neuhäuser M. , Wandira JA, Göttmann U., et al. Utilization of Nacetyl-L-tyrosine and glycyl-L-tyrosine during long-term parenteral nutrition in the growing rat. Am J Clin Nutr1985;42:585-96.
40.
Albers S., Abele R., Amberger I., et al. Komplette parenterale Ernährung mit und ohne einem synthetischen Dipeptid (L-alanyl-L-glutamin) bei Ratten mit Verbrennungen. Akt Ernaehr1984;9:147-9.
41.
Luft G., Stehle P., Fürst P.In vivo utilization of cystine-containing short chain peptides during TPN in rats [Abstract]. Clin Nutr1991;10(suppl 2):11.
42.
Karner J., Roth E., Ollenschläger G., et al. Glutamine-containing dipeptides as infusion substrates in the septic state. Surgery1989;106:893-900.
43.
Babst R., Hörig H., Stehle P., et al. Effects of glutamine supplementation on tissue glutamine concentrations and tissue morphology in long term TPN of growing rats [Abstract]. Clin Nutr1992;11(suppl):86.
44.
Stehle P., Albers S., Fürst P.Stress-induzierte Erniedrigung des intrazellulären Glutamin-Pools-Der potentielle Einsatz von Glutamin-haltigen Peptiden im Rahmen einer parenteralen Ernährung . Akt Ernaehr1988;13:183-9.
45.
Roth E., Karner J., Ollenschläger G., et al. Alanylglutamine reduces muscle loss of alanine and glutamine in postoperative anaesthetized dogs. Clin Sci1988;75:641-8.
46.
Tamada H., Nezu R., Imamura I., et al. The dipeptide alanylglutamine prevents intestinal mucosal atrophy in parenterally fed rats. JPEN1992;16:110-6.
47.
Fürst P.Regulation of intracellular metabolism of amino acids. In: Bozetti F, Dionigi R, eds. Nutrition in trauma and cancer sepsis. Basel : Karger, 1985:21-53.
Albers S., Wernerman J., Stehle P., et al. Availability of amino acids supplied intravenously in healthy man as synthetic dipeptides: kinetic evaluation of L-alanyl-L-glutamine and glycyl-L-tyrosine. Clin Sci1988;75:463-468.
50.
Druml W., Lochs H., Roth E., et al. Utilization of tyrosine dipeptides and acetyltyrosine in normal and uremic humans. Am J Physiol1991;260:E280-5.
51.
Albers S., Wernerman J., Stehle P., et al. Availability of amino acids supplied by constant intravenous infusion of synthetic dipeptides in healthy man. Clin Sci1989;76:643-8.
52.
Hübl W. , Druml W., Langer K., et al. Influence of molecular structure and plasma hydrolysis on the metabolism of glutamine-containing dipeptides in humans. Metabolism1989;38(suppl 1):59-62.
53.
Roth E.Veränderungen im Aminosäuren- und Proteinstoffwechsel bei chirurgischen Patienten. Muenchen: W. Zuckschwerdt, 1986:1-117.
54.
Brandl M., Sailer D., Langer K., et al. Parenteral nutrition with an amino acid solution containing a mixture of dipeptides in man. Contrib Infusion Ther Clin Nutr1987;17:103-15.
55.
Lochs H., Hübl W., Gasic S., et al. Glycylglutamine: metabolism and effects on organ balances of amino acids in postabsorptive and starved subjects. Am J Physiol1992;262:E155-60.
56.
Lochs H., Roth E., Gasic S., et al. Splanchnic, renal, and muscle clearance of alanylglutamine in man and organ fluxes of alanine and glutamine when infused in free and peptide forms. Metabolism1990;39:833-6.
57.
Jepson MM, Bates PC, Broadbent P., et al. Relationship between glutamine concentration and protein synthesis in rat skeletal muscle. Am J Physiol1988;255:E166-72.
58.
Rennie MJ, Hundal HS, Babji P., et al. Characteristics of a glutamine carrier in skeletal muscle have important consequences for nitrogen loss in injury, infection, and chronic disease. Lancet1986;2:1008-11.
59.
MacLennan PA , Brown RA, Rennie MJA positive relationship between protein synthetic rate and intracellular glutamine concentration in perfused rat skeletal muscle . FEBS Lett1987 ;215:187-91.
60.
Stehle P., Zander J., Mertes N., et al. Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet1989;1:231-3.
61.
Hammarqvist F., Wernerman J., Von der Decken A., et al. Alanylglutamine counteracts the depletion of free glutamine and the postoperative decline in protein synthesis in skeletal muscle. Ann Surg1990;212:637-44.
62.
Barua JM, Wilson E., Downie S., et al. The effect of alanylglutamine peptide supplementation on muscle protein synthesis in post-surgical patients receiving glutamine-free amino acids intravenously [Abstract]. Proc Nutr Soc1992;51:104A.
63.
Karner J., Roth E., Stehle P., et al. Influence of glutamine-containing dipeptides on muscle amino acid metabolism. In: Hartig W, Dietze G, Weiner R, et al, eds. Nutrition in clinical practice. Basel : Karger, 1989:56-70.
Petersson B. , Waller S-O., Von der Decken A., et al. The long-term effect of postoperative TPN supplemented with glycyl-glutamine on protein synthesis in skeletal muscle [Abstract]. Clin Nutr1991;10(suppl 2):10.
66.
Tremel H., Kienle B., Weilemann LS, et al. Glutamine dipeptide supplemented TPN maintains intestinal function in critically ill [Abstract]. Clin Nutr1992 ;11:25.
67.
Kapadia CR, Mühlbacher F., Smith RJ, et al. Alterations in glutamine metabolism in response to operative stress and food deprivation. Surg Forum1982 ;33:19-21.
68.
Souba WW, Wilmore DWPostoperative alteration of arteriovenous exchange of amino acids across the gastrointestinal tract. Surgery1983;94:342-50.
69.
Souba WW, Smith RJ, Wilmore DWEffects ofglucocorticoids on glutamine metabolism in visceral organs . Metabolism1985;34:450-6.
70.
Newsholme EA , Newsholme P., Curi R., et al. A role for muscle in the immune system and its importance in surgery, trauma, sepsis and burns . Nutrition1988;4:261-8.
71.
Caldwell MDLocal glutamine metabolism in wounds and inflammation . Metabolism1989;38(suppl 1):34-9.
72.
Smith RJ, Wilmore DWGlutamine nutrition and requirements. JPEN1990;14:94S-9S.
73.
Ziegler TR, Young LS, Benfell K., et al. Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study. Ann Intern Med1992;116:821-8.
74.
Steininger R., Karner J., Roth E., et al. Infusion of dipeptides as nutritional substrates for glutamine, tyrosine, and branched-chain amino acids in patients with acute pancreatitis. Metabolism1989;38(suppl 1):78-81.
75.
Karner J., Roth E.Alanylglutamine infusions to patients with acute pancreatitis. Clin Nutr1990;9:43-5.
76.
Roth E., Winkler S., Hölzenbein Th, et al. High load of alanylglutamine in two patients with acute pancreatitis [Abstract]. Clin Nutr1992;11(suppl):82.
77.
Kinney JM, Fürst P., Elwyn DH, et al. The intensive care patient. In: Kinney JM, Jeejeebhoy KN, Hill GL, et al, eds. Nutrition and metabolism in patient care. Philadelphia: WB Saunders, 1988: 656-71.
78.
Vinnars E., Bergström J., Fürst P.Influence of the postoperative state on the intracellular free amino acids in human muscle tissue. Ann Surg1975 ;182:665-71.
79.
Askanazi J. , Carpentier YA, Michelsen CB, et al. Muscle and plasma amino acids following injury. Influence of intercurrent infection. Ann Surg1980;192:78-85.
80.
Ziegler TR, Benfell K., Smith RJ, et al. Safety and metabolic effects of L-glutamine administration in humans. JPEN1990;14:137S-46S.
81.
Lowe DK, Benfell K., Smith RJ, et al. Safety of glutamine-enriched parenteral nutrient solutions in humans. Am J Clin Nutr1990;52:1101-6.
82.
Khan K., Elia M.Factors affecting the stability of L-glutamine in solution. Clin Nutr1991;10:186-92.
83.
Khan K., Hardy G., McElroy B., et al. The stability of L-glutamine in total parenteral nutrition solutions . Clin Nutr1991;10:193-8.
84.
Stehle P., Fürst P.In vitro hydrolysis of glutamine-, tyrosine- and cystine-containing short chain peptides. Clin Nutr1990;9: 37-8.
85.
Herzog B., Frey B., Stehle P., et al. In vitro peptidase activity of different cell fractions of rat mucosa: kinetic studies using glutamine-containing dipeptides [Abstract]. Clin Nutr1991;10(suppl 2):32.
86.
Ahmed A., Herzog B., Stehle P., et al. Skeletal muscle clearance of L-alanyl-L-glutamine: in vitro peptidase activity ofrat sarcolemmal vesicles [Abstract]. Clin Nutr1991;10(suppl 2):10.
87.
Herzog B., Stehle P., Fürst P.In vitro peptidase activity of basolateral membrane vesicles (BLMV) of rat mucosa against glutamine-containing dipeptides [Abstract]. Clin Nutr1992;11(suppl):31.
88.
McCain HW, Bilotta J., Lamster IBEndorphinergic modulation of immune function: potent action of the dipeptide glycyl-L-glutamine. Life Sci1987;41:169-76.
89.
Adibi SA, Paleos GA, Morse ELInfluence of molecular structure on half-life and hydrolysis of dipeptides in plasma: importance of glycine as N-terminal amino acid residue. Metabolism1986;35:830-6.
Lochs H., Hübl W.Metabolic basis for selecting glutamine-containing substrates for parenteral nutrition. JPEN1990;14:114S-7S.
92.
Abumrad NN, Morse EL, Lochs H., et al. Possible sources of glutamine for parenteral nutrition: impact on glutamine metabolism. Am J Physiol1989 ;257:E228-34.
