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Studies of Protein and Amino Acid Metabolism in the Human Liver

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Yearbook of Intensive Care and Emergency Medicine 1999

Part of the book series: Yearbook of Intensive Care and Emergency Medicine ((YEARBOOK,volume 1999))

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Abstract

Protein depletion is a major determinant of clinical outcome in a number of catabolic states. Hence, assessment of protein metabolism is necessary to understand these conditions as well as to evaluate treatment. Since the regulation of synthesis and breakdown of proteins differs between tissues, it is preferable to study the parameters of protein metabolism separately, and at the organ level. In this chapter we will discuss techniques developed to study liver protein metabolism in man. A technique for liver tissue sampling was established during laparoscopic surgery in order to investigate some parameters of human liver protein metabolism, free amino acid concentrations (ion exchange chromatography), and synthesis rates of total liver protein and albumin (stable isotope technique and gas chromatography-mass spectrometry (GC-MS) as well as ribosome analysis). The impact on these parameters of intravenous nutrition, of growth hormone and of the surgical procedure are also discussed.

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References

  1. Leveille G, Chakrabarty K (1967) Diurnal variations in tissue glycogen and liver weight of mealfed rats. J Nutr 93:546–554.

    PubMed  CAS  Google Scholar 

  2. Garlick PJ, Millward DJ, James WPT, Waterlow JC (1975) The effect of protein deprivation and starvation on the rate of protein synthesis in tissues of the rat. Biochim Biophys Acta 414:71–84.

    Article  PubMed  CAS  Google Scholar 

  3. Hasseigren PO, Jagenburg R, Karlström L, Pedersen P, Seeman T (1984) Changes of protein metabolism in liver and skeletal muscle following trauma complicated by sepsis. J Trauma 24:224–228.

    Article  Google Scholar 

  4. Jepson MM, Pell JM, Bates PC, Millward DJ (1986) The effects of endotoxaemia on protein metabolism in skeletal muscle and liver of fed and fasted rats. Biochem J 235:329–336.

    PubMed  CAS  Google Scholar 

  5. Pain VM, Randall DP, Garlick PJ (1984) Protein synthesis in liver and skeletal muscle of mice bearing an ascites tumor. Cancer Res 44:1054–1057.

    PubMed  CAS  Google Scholar 

  6. Breuille D, Rose F, Arnal M, Melin C, Obled C (1994) Sepsis modifies the contribution of different organs to whole-body protein synthesis in rats. Clin Sci 86:663–669.

    PubMed  CAS  Google Scholar 

  7. Heys SD, Park KGM, McNurlan MA, et al (1992) Protein synthesis rates in colon and liver: stimulation by gastrointestinal pathologies. Gut 33:976–981.

    Article  PubMed  CAS  Google Scholar 

  8. Fearon KCH, McMillan DC, Preston T, Windstanley FP, Cruickshank AM, Shenkin A (1991) Elevated circulating interleukin-6 is associated with an acute-phase response but reduced fixed hepatic protein synthesis in patients with cancer. Ann Surg 213:26–31.

    Article  PubMed  CAS  Google Scholar 

  9. McFarlane A (1963) Measurement of synthesis rates of liver-produced plasma proteins. Biochem J 89:277–289.

    PubMed  CAS  Google Scholar 

  10. Rotschild MA, Oratz M, Screiber SS (1988) Serum albumin. Hepatology 8:385–401.

    Article  Google Scholar 

  11. Ballmer PE, McNurlan MA, Milne E, et al (1990) Measurement of albumin synthesis in humans: a new approach employing stable isotopes. Am J Physiol 259: E797-E803.

    Google Scholar 

  12. Pain V, Clemens MJ, Garlick PJ (1978) The effect of dietary protein deficiency on albumin synthesis and on the concentration of active albumin messenger ribonucleic acid in rat liver. Biochem J 172:129–135.

    PubMed  CAS  Google Scholar 

  13. Hunter KA, Ballmer PE, Anderson SE, Broom J, Garlick PJ, McNurlan MA (1995) Acute stimulation of albumin synthesis rate with oral meal feeding in healthy subjects measured with [ring-2H5]phenylalanine. Clin Sci 88:235–242.

    PubMed  CAS  Google Scholar 

  14. Ballmer PE, Ballmer-Hofer K, Repond F, Kohler H, Studer H (1992) Acute suppression of albumin synthesis in systemic inflammatory disease: an individually graded response of rat hepa-tocytes. J Histochem Cytochem 40:201–206.

    Article  PubMed  CAS  Google Scholar 

  15. Moshage HJ, Janssen JAM, Franssen JH, Hafkenscheid JCM, Yap SH (1987) Study of the molecular mechanism of decreased liver synthesis of albumin in inflammation. J Clin Invest 79: 1635–1641.

    Article  PubMed  CAS  Google Scholar 

  16. McNurlan M, Sandgren A, Hunter K, Essén P, Garlick PJ, Wernerman J (1996) Protein synthesis rates of skeletal muscle, lymphocytes, and albumin with stress hormone infusion in healthy man. Metabolism 45:1388–1394.

    Article  PubMed  CAS  Google Scholar 

  17. van Acker B, Hulsewé KWE, Wagenmakers AJM, Deutz NEP, von Meyenfeldt MF, Soeters PB (1998) Effect of surgery on albumin synthesis rate in humans. Clin Nutr 17:14 (Abst).

    Article  Google Scholar 

  18. Dahn M, Mitchell RA, Lange MP, Smith S, Jacobs LA (1995) Hepatic metabolic response to injury and sepsis. Surgery 117:520–530.

    Article  PubMed  CAS  Google Scholar 

  19. Mansoor O, Cayol M, Gachon P, et al (1997) Albumin synthesis rates increase while muscle protein synthesis decreases in head-injured patients. Am J Physiol 273: E898–E902.

    PubMed  CAS  Google Scholar 

  20. Essén P, McNurlan MA, Gamrin L, et al (1998) Tissue protein synthesis rates in the critically ill. Crit Care Med 26:92–100.

    Article  PubMed  Google Scholar 

  21. Peavy D, Taylor JM, Jefferson LS (1985) Time course of changes in albumin synthesis and mRNA in diabetic and insulin-trated rats. Am J Physiol 248: E656–E663.

    PubMed  CAS  Google Scholar 

  22. Moshage H, Kleter BE, van Pelt JF, Roelofs HM, Kleuskens JA, Yap SH (1988) Fibrinogen and albumin synthesis are regulated at the transcriptional level during the acute phase response. Biochim Biophys Acta 950:450–454.

    Article  PubMed  CAS  Google Scholar 

  23. Maeda K, Schoeniger LO, Shimada M, Winchurch RA, Buchman TG, Robotham JL (1993) Regulation of acute phase gene expression following surgery and endotoxin administration in the anesthetized pig. Anesthesiology 79:1324–1337.

    Article  PubMed  CAS  Google Scholar 

  24. Fleck A, Hawker F, Wallace PI, et al (1985) Increased vascular permeability: a major cause of hypoalbuminemia in disease and injury. Lancet 1:781–784.

    Article  PubMed  CAS  Google Scholar 

  25. Fleck A, Colley CM, Myers MA (1985) Liver export proteins and trauma. Br Med Bull 41:265–273.

    PubMed  CAS  Google Scholar 

  26. Young GA, Chem C, Zeiderman MR, Thompson M, McMahon MI (1989) Influence of preoperative nutrition upon hepatic protein synthesis and plasma proteins and amino acids. J Parenter Enteral Nutr 13:586–602.

    Article  Google Scholar 

  27. de Feo P, Horber FF, Haymond MW (1992) Meal stimulation of albumin synthesis: a significant contributor to whole body protein synthesis in humans. Am J Physiol 263: E794–E799.

    PubMed  Google Scholar 

  28. Skillman J, Rosenoer VM, Smith PC, Fang MS (1976) Improved albumin synthesis in postoperative patients by amino acid infusion. N Engl J Med 295:1037–1040.

    Article  PubMed  CAS  Google Scholar 

  29. Ballmer PE, McNurlan MA, Essén P, Anderson SE, Garlick PJ (1995) Albumin synthesis rates measured with (2H5ring)phenylalanine are not responsive to short-term intravenous nutrients in healthy humans. J Nutr 125:512–519.

    PubMed  CAS  Google Scholar 

  30. Herndon D, Barrow RE, Kunkel KR, Broemeling L, Rutan RL (1990) Effects of recombinant human growth hormone on donor-site healing in severely burned children. Ann Surg 212:424–429.

    Article  PubMed  CAS  Google Scholar 

  31. Liljedahl SO, Gemzell CA, Plantin LO, Birke G (1961) Effect of growth hormone in patients with severe burns. Acta Chir Scand 122:1–14.

    PubMed  CAS  Google Scholar 

  32. Jiang ZM, He GZ, Zhang SY, et al (1989) Low-dose growth hormone and hypocaloric nutrition attenuate the protein-catabolic response after major operation. Ann Surg 210:513–524.

    Article  PubMed  CAS  Google Scholar 

  33. Mjaaland M, Unneberg K, Hotvedt R, Revhaug A (1991) Nitrogen retention caused by growth hormone in patients undergoing gastrointestinal surgery with epidural analgesia and parenteral nutrition. Eur J Surg 157:21–27.

    PubMed  CAS  Google Scholar 

  34. Hammarqvist F, Strömberg C, von der Decken A, Vinnars E, Wernerman J (1992) Biosynthetic growth hormone preserves both muscle protein synthesis and decrease in muscle free glutamine, and improves whole-body nitrogen economy after operation. Ann Surg 216:184–191.

    Article  PubMed  CAS  Google Scholar 

  35. Voerman HJ, Strack van Schijndel RJM, Groenenvald ABJ, et al (1992) Effects of recombinant human growth hormone in patients with severe sepsis. Ann Surg 216:648–655.

    Article  PubMed  CAS  Google Scholar 

  36. Dahn MS, Lange P, Jacobs LA (1988) Insulin like growth factor I production is inhibited in human sepsis. Arch Surg 123:1409–1414.

    Article  PubMed  CAS  Google Scholar 

  37. Roth E, Valentini L, Semsroth M, Hšlzenbein T, Winkler S, Blum WF (1995) Resistance of nitrogen metabolism to growth hormone treatment in the early phase of after injury of patients with multiple injuries. J Trauma 38:136–141.

    Article  PubMed  CAS  Google Scholar 

  38. Clemens M, Korner A (1970) Amino acid requirements for the growth-hormone stimulation of incorporation of precursors into protein and nucleic acids of liver slices. Biochem J 119: 629–634.

    PubMed  CAS  Google Scholar 

  39. Korner A (1960) The effect of hypophysectomy of the rat and the treatment with growth hormone on the incorporation in vivo of radioactive amino acids into proteins of the subcellular fractions of the liver. Biochem J 74:462–471.

    PubMed  CAS  Google Scholar 

  40. Pella J, Bates PC (1992) Differential actions of growth hormone and insulin-like growth factor-I on tissue protein metabolism in dwarf mice. Endocrinol 130:1942–1950.

    Article  Google Scholar 

  41. Jeejeebhoy K, Bruce-Robertson A, Ho J, Sodtke U (1972) The comparative effects of nutritional and hormonal factors on albumin, fibrinogen and transferrin. Ciba Foundation Symposium 9:217–247.

    PubMed  CAS  Google Scholar 

  42. Keller G, Taylor JM (1976) Effect of hyophysectomy on the synthesis of rat liver albumin. J Biol Chem 251:3768–3773.

    PubMed  CAS  Google Scholar 

  43. McNurlan MA, Garlick PJ, Steigbigel RT, et al (1997) Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease. J Clin Invest 100:2125–2132.

    Article  PubMed  CAS  Google Scholar 

  44. Zachwieja J, Bier DM, Yarasheski KE (1994) Growth hormone administration in older adults: effects on albumin synthesis. Am J Physiol 6: E840–E844.

    Google Scholar 

  45. Olufemi OS, Humes P, Whittaker PG, Read MA, Lind T, Halliday D (1990) Albumin synthetic rate: a comparison of arginine and alpha-ketoisocaproate precursor methods using stable isotope techniques. Eur J Clin Nutr 44:351–361.

    PubMed  CAS  Google Scholar 

  46. Barle H, Ahlman B, Nyberg B, Andersson K, Essén P, Wernerman J (1996) The concentrations of free amino acids in human liver tissue obtained during laparoscopic surgery. Clin Physiol 16:217–227.

    Article  PubMed  CAS  Google Scholar 

  47. Barle H, Nyberg B, Essén P, et al (1997) The synthesis rates of total liver protein and plasma albumin determined simultaneously in vivo in man. Hepatology 25:154–158.

    PubMed  CAS  Google Scholar 

  48. Barle H, Nyberg B, Andersson K, et al (1997) The effects of short-term parenteral nutrition on human liver protein and amino acid metabolism during laparoscopic surgery. J Parenter Enteral Nutr 21:330–335.

    Article  CAS  Google Scholar 

  49. Barle H, Andersson K, Essén P, et al (1997) Growth hormone, but not parenteral nutrition, stimulates the fractional synthesis rate of albumin. Hygiea 106:116 (Abst).

    Google Scholar 

  50. Barle H, Nyberg B, Essén P, et al (1996) Growth hormone regulates human liver protein metabolism. Clin Nutr 15(suppl 1):4 (Abst).

    Article  Google Scholar 

  51. Barle H, Nyberg B, Essén P, et al (1998) Growth hormone stimulates albumin synthesis in man. Intensive Care Med 24: S13 (Abst).

    Google Scholar 

  52. Barle H, Nyberg B, Ramel S, Essen P, McNurlan MA, Wernerman J, Garlick PJ (1998) The synthesis rates of total liver protein, but not of albumin, decrease during a surgical trauma. Clin Nutr 17(suppll):15(Abst).

    Article  Google Scholar 

  53. Hammarqvist F, Strömberg C, von der Decken A, Vinnars E, Wernerman J (1992) Biosynthetic human growth hormone preserves both muscle protein synthesis and the decrease in muscle-free glutamine, and improves whole body nitrogen economy after operation. Ann Surg 216:184–191.

    Article  PubMed  CAS  Google Scholar 

  54. Ahlman B, Leijonmarck C-E, Wernerman J (1993) The content of free amino acids in the human duodenal mucosa. Clin Nutr 12:266–271.

    Article  PubMed  CAS  Google Scholar 

  55. Lunn PG, Whitehead RG, Baker BA (1976) The relative effects of a low protein high carbohydrate diet on the free amino acid composition of liver and muscle. Br J Nutr 36:219–230.

    Article  PubMed  CAS  Google Scholar 

  56. Wernerman J, Barle H, Hammarqvist F (1998) Tissue specific effects of growth hormone on protein metabolism. J Growth Hormone IGF Res 8:111–113.

    Article  CAS  Google Scholar 

  57. McMillan D, Slater C, Preston T, Falconer JS, Fearon KCH (1996) Simultaneous measurement of fibrinogen and albumin synthetic rates in normal fasted subjects. Nutrition 12:602–607.

    Article  PubMed  CAS  Google Scholar 

  58. Gersovitz M, Munro HN, Udall J, Young VR (1980) Albumin synthesis in young and elderly subjects using a new stable isotope methodology: response to level of protein intake. Metabolism 29:1075–1086.

    Article  PubMed  CAS  Google Scholar 

  59. Mansoor O, Beaufrère B, Boirie Y, et al (1996) Increased mRNA levels for components of the lysosomal, Ca2+-activated, and ATP-ubiquitin-dependent proteolytic pathways in skeletal muscle from head trauma patients. Proc Natl Acad Sci USA 93:2714–2718.

    Article  PubMed  CAS  Google Scholar 

  60. Mortimore G, Poso AR, Lardeux BR (1989) Mechanism and regulation of protein degradation in the liver. Diabetes Metab Rev 5:49–70.

    Article  PubMed  CAS  Google Scholar 

  61. Ballmer PE, Weber BK, Roy-Chaudhury P, et al (1992) Elevation of albumin synthesis rates in nephrotic patients measured with [l-13C]leucine. Kidney Int 41:132–138.

    Article  PubMed  CAS  Google Scholar 

  62. Barle H, Gamrin L, Essén P, McNurlan MA, Wernerman J, Garlick PJ (1998) Growth hormone does not affect albumin synthesis in the critically ill. Clin Nutr 17(suppl 1):67 (Abst).

    Article  Google Scholar 

  63. Garlick P, McNurlan MA, Essén P, Wernerman J (1994) Measurement of tissue protein syntheis rates in vivo: a critical analysis of contrasting methods. Am J Physiol 266: E287–E297.

    PubMed  CAS  Google Scholar 

  64. Ljungqvist O, Persson M, Ford GC, Nair KS (1997) Functional heterogeneity of leucine pools in human skeletal muscle. Am J Physiol 272: E564–E570.

    Google Scholar 

  65. Cayol M, Boirie Y, Prugnaud J, Gachon P, Beaufrère B, Obled C (1996) Precursor pool for hepatic protein synthesis: effects of tracer route infusion and dietary proteins. Am J Physiol 270: E980–E987.

    PubMed  CAS  Google Scholar 

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Authors
  1. H. Barle
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  2. P. Essén
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  3. J. Wernerman
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Editors and Affiliations

  1. Department of Intensive Care, Erasme Hospital, Free University of Brussels, Route de Lennik 808, B-1070, Brussels, Belgium

    Jean-Louis Vincent (Clinical Director) (Clinical Director)

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© 1999 Springer-Verlag Berlin Heidelberg

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Barle, H., Essén, P., Wernerman, J. (1999). Studies of Protein and Amino Acid Metabolism in the Human Liver. In: Vincent, JL. (eds) Yearbook of Intensive Care and Emergency Medicine 1999. Yearbook of Intensive Care and Emergency Medicine, vol 1999. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-13453-5_8

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  • DOI: https://doi.org/10.1007/978-3-662-13453-5_8

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-65288-5

  • Online ISBN: 978-3-662-13453-5

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