Advertisement

The Metabolic Fate of Branched-Chain Amino Acids

  • E. Holm
  • H. Leweling
  • U. Staedt
  • J.-P. Striebel
  • St. Jacob

Abstract

This contribution is, at first, concerned with data which indicate that portal-systemic shunting (PSS) of blood and hepatic failure exert differential effects on the plasma levels of branched-chain amino acids (BCAA). Following this, recent findings pertaining to amino acid clearance rates in cirrhotic patients are presented. Special interest is given to metabolic mechanisms underlying the reduction in the plasma levels of BCAA in patients with liver cirrhosis and in animals with portocaval anastomosis (PCA). From the metabolic alterations outlined, provisional therapeutic principles can be derived. Finally, the concentrations of BCAA produced in plasma and muscle by therapeutic administration of these substances require a brief discussion.

Keywords

Hepatic Encephalopathy Cirrhotic Patient Amino Acid Concentration Plasma Amino Acid Portacaval Shunt 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Y. Iwasaki, H. Sato, A. Ohkubo, T. Sanjo, S. Futagawa, M. Sugiura, and S. Tsuji, Effect of spontaneous portal-systemic shunting on plasma insulin and amino acid concentrations, Gastroenterology 78: 677 (1980).PubMedGoogle Scholar
  2. 2.
    A. Aguirre, N. Yoshimura, T. Westman, and J. E. Fischer, Plasma amino acids in dogs with two experimental forms of liver damage, J. Surg. Res. 16: 339 (1974).PubMedCrossRefGoogle Scholar
  3. 3.
    E. Holm, J.-P. Striebel, R. Münzenmaier, and R. Kattermann, Pathogenese der hepatischen Enzephalopathie, Leber Magen Darm 7: 241 (1977).PubMedGoogle Scholar
  4. 4.
    E. Holm, J.-P. Striebel, W. Langhans, R. Kattermann, and B. Werner, Beziehunger zwischen Plasmaammoniak, Plasmaaminosauren und weiteren Parametern bei Leberzirrhose. Zwei Hauptkomponentenanalysen, Verh. dt. Ges. inn. Med. 86: 775 (1980).Google Scholar
  5. 5.
    R. Herz, M. Rössle, U. Schulte, and W. Gerok, Periphere Aminosäuren-Konzentrationen bei eingeschränkter quantitativer Leberfunktion infolge Leberzirrhose, Z. Gastroenterol. 17: 586 (1979).Google Scholar
  6. 6.
    E. Holm, J.-P. Striebel, R. Kattermann, E. Schick, and U. Staedt, Encephalopathy resulting from portacaval anastomosis in cats. Ammonia, amino acids, and cerebral electrical activity, ln:Amino Acid and Ammonia Metabolism in Hepatic Failure“, E. Holm, ed., Witzstrock, Baden-Baden–Köln–New York (1982), pp. 58–94.Google Scholar
  7. 7.
    H. Leweling, and E. Holm, in preparation.Google Scholar
  8. 8.
    L. L. Miller, The role of the liver and the non-hepatic tissues in the regulation of free amino acid levels in the blood, in:“Amino Acid Pools”, J. T. Holden, ed., Elsevier, Amsterdam–London–New York (1962), pp. 708–721.Google Scholar
  9. 9.
    A. E. Harper and C. Zapalowski, Interorgan relationships in the metabolism of the branched-chain amino and alpha-ketoacids, in:“Metabolism and Clinical Implications of Branched Chain Amino and Ketoacids,” M. Walser and J. R. Williamson, eds., Elsevier/North-Holland, New York - Amsterdam - Oxford pp. 195–203 (1981).Google Scholar
  10. 10.
    S. A. Adibi, Metabolism of branched-chain amino acids in altered nutrition, Metabolism 25: 1287 (1976).PubMedCrossRefGoogle Scholar
  11. 11.
    H. M. Goodman and G. P. Frick, Metabolism of branched chain amino acids in adipose tissue, in:’Metabolism and Clinical Implications of Branched Chain Amino and Ketoacids,“ M. Walser and J. R. Williamson, eds., Elsevier/North-Holland, New York-Amsterdam - Oxford, pp. 169–180 (1981).Google Scholar
  12. 12.
    K. Brand, Metabolism of alpha-keto acid analogues of leucine, valine and phenylalanine in extrahepatic and hepatic tissues, in:’Metabolism and Clinical Implications of Branched Chain Amino and Ketoacids,“ M. Walser and J. R. Williamson, eds., Elsevier/North-Holland, New York - Amsterdam - Oxford, pp. 135–142 (1981).Google Scholar
  13. 13.
    R. Sherwin, P. Joshi, R. Hendler, Ph. Felig, and H. 0. Conn, Hyperglucagonemia in Laennec’s cirrhosis, New Engl. J. Med. 290: 239 (1974).PubMedCrossRefGoogle Scholar
  14. 14.
    G. Smith-Laing, The glucoregulatory hormones in cirrhosis of the liver, Z. Gastroenterol. 7: 462 (1979).Google Scholar
  15. 15.
    P. B. Soeters, G. Weir, A. M. Ebeid, and J. E. Fischer, Insulin, glucagon, portal systemic shunting and hepatic failure in the dog, J. Surg. Res. 23: 183 (1977).PubMedCrossRefGoogle Scholar
  16. 16.
    J. H. James, V. Ziparo, B. Jeppson, and J. E. Fischer, Hyperammonaemia, plasma aminoacid imbalance, and blood-brain aminoacid transport: a unified theory of portal-systemic encephalopathy, Lancet 2: 772 (1979).PubMedCrossRefGoogle Scholar
  17. 17.
    H. N. Munroe, J. D. Fernstrom, and R. J. Wurtman, Plasma amino acid imbalance and hepatic coma, in: “Klin. Anästhesiol. Intensivther.”Bd. 13, F. W. Ahnefeld, H. Bergmann, C. Burri, W. Dick, M. Halmagyi, and E. Rügheimer, eds., Springer, Berlin-Heidelberg-New York, pp. 103–112 (1977).Google Scholar
  18. 18.
    A. L. Goldberg and T. W. Chang, Regulation and significance of amino acid metabolism in skeletal muscle, Fed. Proc. 37: 2301 (1978).PubMedGoogle Scholar
  19. 19.
    M. Berger, H. Zimmernann-Telschow, P. Berchtold, H. Drost, W. A. Muller, F. A. Gries, and H. Zimmermann, Blood amino acid levels in patients with insulin excess (functioning insulinoma) and insulin deficiency (diabetic ketosis), Metabolism 27: 793 (1978).PubMedCrossRefGoogle Scholar
  20. 20.
    G. Kleinberger, P. Ferenci, A. Gassner, M. Pichler, and H. Lochs, Unterschiede im Plasmaaminogramm bei Coma hepaticum and Coma diabeticum, Z. Gastroenterol. 16: 752 (1978).PubMedGoogle Scholar
  21. 21.
    Ph. Felig, Amino acid metabolism in man, Ann. Rev. Biochem. 44: 933 (1975).PubMedCrossRefGoogle Scholar
  22. 22.
    Ph. Felig, O. E. Owen, J. Wahren, and G. F. Cahill, Amino acid metabolism during prolonged starvation, J. Clin. Invest. 48: 584 (1969).PubMedCrossRefGoogle Scholar
  23. 23.
    T. Pozefsky, R. G. Tancredi, R. T. Moxley, J. Dupre, and J. D. Tobin, Effects of brief starvation on muscle amino acid metabolism in nonobese man, J. Clin. Invest. 57: 444 (1976).PubMedCrossRefGoogle Scholar
  24. 24.
    B. Limberg and B. Kommerell, Why decreased serum branched-chain amino acids in cirrhosis, Gastroenterology 80: 211 (1981).PubMedGoogle Scholar
  25. 25.
    P. B. Soeters, J. E. G. de Boer, R. J. Oostenbroek, and M. A. Janssen, Fate of branched chain amino acids, in:“New Aspects of Clinical Nutrition.” G. Kleinberger, and E. Deutsch, eds., Karger, Basel, pp. 337–345 (1983).Google Scholar
  26. 26.
    P. B. Soeters, J. Hodgman, J. H. James, and J. E. Fischer, Increased catabolism of branched chain amino acids following portacaval shunt, Gastroenterology 69: 867 (1975).Google Scholar
  27. 27.
    T. Pozefsky, Ph. Felig, J. D. Tobin, J. S. Soeldner, and G. F. Cahill, Amino acid balance across tissues of the forearm in postabsorptive man. Effects of insulin at two dose levels, J. Clin. Invest. 48: 2273 (1969).PubMedCrossRefGoogle Scholar
  28. 28.
    G. Marchesini, G. Forlani, M. Zoli, A. Angiolini, M. P. Scolari, F. B. Bianchi, and E. Pisi, Insulin and Glucagon levels in liver cirrhosis. Relationship with plasma amino acid imbalance of chronic hepatic encephalopathy, Digest. Dis. Sci. 24: 594 (1979).PubMedCrossRefGoogle Scholar
  29. 29.
    E. Holm, unpublished data.Google Scholar
  30. 30.
    D. R. Strombeck, Q. Rogers, and J. S. Stern, Effects of intravenous ammonia infusion on plasma levels of amino acids, glucagon and insulin in dogs, Gastroenterology 74: 1165 (1978).Google Scholar
  31. 31.
    S. A. Adibi, Roles of branched-chain amino acids in metabolic regulation, J. Lab. Clin. Med. 95: 475 (1980).PubMedGoogle Scholar
  32. 32.
    S. A. Adibi, R. T. Stanko, and E. L. Morse, Modulation of leucine oxidation and turnover by graded amounts of carbohydrate intake in obese subjects, Metabolism 31: 578 (1982).PubMedCrossRefGoogle Scholar
  33. 33.
    S. M.Hutson, C. Zapalowski, Th. C. Cree, and A. E. Harper, Regulation of leucine and alpha-ketoisocaproic acid metabolism in skeletal muscle, J. Biol. Chem. 255: 3418 (1980).Google Scholar
  34. 34.
    R. Odessey, E. A. Khairallah, and A. L. Goldberg, Origin and possible significance of alanine production by skeletal muscle, J. Biol. Chem. 249: 7623 (1974).PubMedGoogle Scholar
  35. 35.
    G. Marchesini, G. Forlani, and M. Zoli, Iperinsulinismo e caduta degli aminoacidi a catena ramificata nel cirrotico: causa ed effetto? II fegato 27: 197 (1981).Google Scholar
  36. 36.
    V. Brodan, M. Brodanova, M. Andel, and E. Kuhn, The effect of glucagon on free plasma amino acids in cirrhotics and healthy controls, Acta Hepato-Gastroenterol. 25: 23 (1978).Google Scholar
  37. 37.
    P. M. Daniel, O. E. Pratt, and E. Spargo, The mechanisms by which glucagon induces the release of amino acids from muscle and its relevance to fasting, Proc. R. Soc. London B 196: 347 (1977).CrossRefGoogle Scholar
  38. 38.
    E. Spargo, O. E. Pratt, and P. M. Daniel, Metabolic functions of skeletal muscles of man, mammals, birds and fishes: a review, J. Roy. Soc. Med. 72: 921 (1979).PubMedGoogle Scholar
  39. 39.
    M. C. Schaeffer, Q. R. Rogers, B. M. Wolfe, and R. A. LeCouteur, Effects of glutamine feeding on plasma and cerebrospinal fluid ammonia and amino acids in portacaval shunt dogs. 12th Int. Congr. Nutr., San Diego,- Abstract Book, No. 840 (1981).Google Scholar
  40. 40.
    E. Holm, H. Leweling, and U. Staedt, Metabolism and nutritional supply of amino acids in hepatic failure, in:“New Aspects of Clinical Nutrition,” G. Kleinberger and E. Deutsch., eds., Karger, Basel, pp. 377–399 (1983).Google Scholar
  41. 41.
    E. Holm, J.-P. Striebel, E. Meisinger, P. Haux, W. Langhans, and H. D. Becker, Aminosäurengemische zur parenteralen Ernährung bei Leberinsuffizienz, Infusionstherapie 5: 274 (1978).Google Scholar
  42. 42.
    M. Imler, J. L. Schlienger, A. Frick, A. Stahl, and G. Chabrier, Study of muscular glutamine and alanine release in cirrhotics with hyperammonemia and in ammonium infused rats, in:“Aminosäuren-und Ammoniakstoffwechsel bei Leberinsuffizienz,” E. Holm, ed., Witzstrock, Baden-Baden-KiSln-New York, pp. 33–39 (1982).Google Scholar
  43. 43.
    M. Elia and G. Livesey, Branched chain amino acid and oxo acid metabolism in human and rat muscle, in:“Metabolism and Clinical Implications of Branched Chain Amino and Ketoacids,” M. Walser and J. R. Williamson, eds., Elsevier/North-Holland, New York-Amsterdam-Oxford, pp. 257–262 (1981).Google Scholar
  44. 44.
    D. E. Matthews, H. P. Schwarz, R. D. Yang, K. J. Motil, V. R. Young, and D. M. Bier, Relationship of plasma leucine and alpha-ketoisocaproate during a L-(1–13C)leucine infusion in man: A method for measuring human intracellular leucine tracer enrichment, Metabolism 31: 1105 (1982).PubMedCrossRefGoogle Scholar
  45. 45.
    P. Schauder, K. Schrader, H. V. Henning, and U. Langenbeck, Some aspects on the role of branched chain keto acids in the pathophysiology and treatment of uremia. Convegno internazionale su “Problemi metabolici e nutrizionali nell’insufficienza renale e epatica”, Parma 1982, in press.Google Scholar
  46. 46.
    D. L. Bloxam, Nutritional aspects of amino acid metabolism. 2. The effects of starvation on hepatic portal-venous differences in plasma amino acid concentration and on liver amino acid concentrations in the rat, Br. J. Nutr. 27: 233 (1972).PubMedCrossRefGoogle Scholar
  47. 47.
    P. Ferenci, B. Dragosics, and F. Wewalka, Oral administration of branched chain amino acids (BCAA) and keto acids (BCKA) in patients with liver cirrhosis (LC), in:“Metabolism and Clinical Implications of Branched Chain Amino and Ketoacids,” M. Walser and J. R. Williamson, eds., Elsevier/North-Holland, New York-Amsterdam-Oxford, pp. 507–512 (1981).Google Scholar
  48. 48.
    J. Bergström, P. Fürst, L.-0. Norée, and E. Vinnars, Intracellular free amino acid concentration in human muscle tissue, J. Appl. Physiol. 36: 693 (1974).PubMedGoogle Scholar
  49. 49.
    P. Fürst, personal coliuuunication, (1982).Google Scholar
  50. 50.
    U. Staedt, E. Holm, J.-P. Striebel, and P. Gasteiger, Amino acid concentrations in plasma and intracellular water of muscle in cats given a portacaval anastomosis. Effects of brief intravenous nutrition including a BCAA-enriched solution, Clin. Nutr. 1: F 52 (1982).Google Scholar
  51. 51.
    J. E. G. de Boer, R. J. Oostenbroek, M. A. Janssen, R. I. C. Wesdorp, and P. B. Soeters, Fate of leucine in muscle and adipose tissue in male Sprague-Dawley rats with portacaval shunts (PCS), Clin. Nutr. 1: F 51 (1982).Google Scholar
  52. 52.
    E. Roth, personal communication,(1982).Google Scholar
  53. 53.
    E. Mezey, Liver disease and nutrition, Gastroenterology 74: 770 (1978).PubMedGoogle Scholar
  54. 54.
    P. J. Randle, P. B. Garland, C. N. Hales, and E. A. Newsholme, The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus, Lancet 1: 785 (1963).PubMedCrossRefGoogle Scholar
  55. 55.
    P. B. Soeters and J. E. Fischer, Insulin, glucagon, amino-acid imbalance, and hepatic encephalopathy, Lancet 2: 880 (1976).PubMedCrossRefGoogle Scholar
  56. 56.
    J. E. Fischer, J. M. Funovics, A. Aguirre, J. H. James, J. M. Keane, R. I. C. Wesdorp, N. Yoshimura, and Th. Westman, The role of plasma amino acids in hepatic encephalopathy, Surgery 78: 276 (1975).PubMedGoogle Scholar
  57. 57.
    J. E. Fischer, H. M. Rosen, A. M. Ebeid, J. H. James, J. M. Keane, and P. B. Soeters, The effect of normalization of plasma amino acids on hepatic encephalopathy in man, Surgery 80: 77 (1976).PubMedGoogle Scholar
  58. 58.
    E. Holm, Parenteral nutrition in patients with hepatic failure, J. Drug. Res. 6: 41 (1981).Google Scholar
  59. 59.
    E. Holm, Behandlungen mit Aminosäuren bei hepatischer Enzephalopathie, Fischer, Stuttgart-New York (1976).Google Scholar
  60. 60.
    H. Leweling, E. Holm, U. Staedt, H. Feussner, O. Zelder, and J.-P. Striebel, Totale parenterale Ernährung bei Ratten mit portokavaler Anastomose, Infusionsther. Klin. Ern. 9: 234 (1982).Google Scholar
  61. 61.
    E. Holm, BCAA-enriched diets for oral treatment of patients with liver cirrhosis: A controlled study of biochemical variables, psychometric performance, and the EEG. Ajinomoto Symp., Abstract Book, Raleigh (1982).Google Scholar
  62. 62.
    D. Horst, N. Grace, H. O. Conn, E. Schiff, S. Schenker, A. Viteri, D. Law, and C. E. Atterbury, A double-blind randomized comparison of dietary protein and an oral branched-chain amino acid (BCAA) solution in cirrhotic patients with chronic portal-systemic encephalopathy, Congr. IASL, Abstract Book, No. 157, Hong Kong (1982).Google Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • E. Holm
    • 1
  • H. Leweling
    • 1
  • U. Staedt
    • 1
  • J.-P. Striebel
    • 1
  • St. Jacob
    • 1
  1. 1.Dept. of Pathophysiology, 1st Med. Clinic MannheimUniversity of HeidelbergGermany

Personalised recommendations