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Mechanism and Control of Deprivation-Induced Protein Degradation in Liver: Role of Glucogenic Amino Acids

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Glutamine Metabolism in Mammalian Tissues

Abstract

In addition to the amino acid requirement for protein synthesis, all animals need an extra supply to replace irreversible amino acid losses by gluconeogenesis and other ongoing, oxidative and biosynthetic reactions. During intestinal absorption, this need is met by the breakdown of ingested proteins, but when absorption ceases, internal sources must be called into play. Because free amino acids are not stored in mammalian cells or extracellular spaces to any significant extent, this supply (or its nitrogen equivalent) can only come from the degradation of endogenous proteins.

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References

  1. White A (1947) Protein metabolism. In: Duncan RT (ed) Diseases of metabolism. Saunders, Philadelphia, pp 83–157

    Google Scholar 

  2. Addis T, Poo LJ, Lew W (1936) The quantities of protein lost by the various organs and tissues of the body during a fast. J Biol Chem 115: 111–118

    CAS  Google Scholar 

  3. Soberón G, Sánchez QE (1961) Changes in effective enzyme concentration in the growing rat liver. J Biol Chem 236: 1602–1606

    Google Scholar 

  4. Hutson NJ, Mortimore GE (1982) Suppression of cytoplasmic protein uptake by lysosomes as the mechanism of protein regain in livers of starved-refed mice. J Biol Chem 257: 9548–9554

    PubMed  CAS  Google Scholar 

  5. Mortimore GE, Hutson NJ, Surmacz CA (1983) Quantitative correlation between proteolysis and macro- and microautophagy in mouse hepatocytes during starvation and refeeding. Proc Natl Acad Sci USA 80: 2179–2183

    Article  PubMed  CAS  Google Scholar 

  6. Millward DJ, Nnanyelugo DO, James WPT, Garlick PJ (1974) Protein metabolism in skeletal muscle: The effect of feeding and fasting on muscle RNA, free amino acids and plasma insulin concentrations. Br J Nutr 32: 127–142

    Article  PubMed  CAS  Google Scholar 

  7. Millward DJ, Waterlow JC (1978) Effect of nutrition on protein turnover in skeletal muscle. Fed Proc 37: 2283–2289

    PubMed  CAS  Google Scholar 

  8. Mortimore GE, Mondon CE (1970) Inhibition by insulin of valine turnover in liver. J Biol Chem 245: 2375–2383

    PubMed  CAS  Google Scholar 

  9. Woodside KH, Mortimore GE (1972) Supression of protein turnover by amino acids in the perfused rat liver. J Biol Chem 247: 6474–6481

    PubMed  CAS  Google Scholar 

  10. Garlick PJ, Millward DJ, James WPT (1973) The diurnal response of muscle and liver protein synthesis in vivo in meal-fed rats. Biochem J 136: 935–945

    PubMed  CAS  Google Scholar 

  11. Garlick PJ, Millward DJ, James WPT, Waterlow J (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

    PubMed  CAS  Google Scholar 

  12. Conde RD, Scornik OA (1976) Role of protein degradation in the growth of livers after a nutritional shift. Biochem J 158: 385–390

    PubMed  CAS  Google Scholar 

  13. Ward WF, Cox JR, Mortimore GE (1977) Lysosomal sequestration of intracellular protein as a regulatory step in hepatic proteolysis. J Biol Chem 252: 6955–6961

    PubMed  CAS  Google Scholar 

  14. Neff NT, DeMartino GN, Goldberg AL (1979) The effect of protease inhibitors and decreased temperature on the degradation of different classes of proteins in cultured hepatocytes. J Cell Physiol 101: 439–458

    Article  PubMed  CAS  Google Scholar 

  15. Grinde B, Seglen PO (1980) Differential effects of proteinase inhibitors and amines on the lysosomal and non-lysosomal pathways of protein degradation in isolated rat hepatocytes. Biochim Biophys Acta 632: 73–86

    Article  PubMed  CAS  Google Scholar 

  16. Schworer CM, Shiffer KA, Mortimore GE (1981) Quantitative relationship between autophagy and proteolysis during graded amino acid deprivation in perfused rat liver. J Biol Chem 256: 7652–7658

    PubMed  CAS  Google Scholar 

  17. Mortimore GE, Ward WF (1981) Internalization of cytoplasmic protein by hepatic lysosomes in basal and deprivation-induced proteolytic states. J Biol Chem 256: 7659–7665

    PubMed  CAS  Google Scholar 

  18. Schworer CM, Mortimore GE (1979) Glucagon-induced autophagy and proteolysis in rat liver: Mediation by selective deprivation of intracellular amino acids. Proc Natl Acad Sci USA 76: 3169–3173

    Article  PubMed  CAS  Google Scholar 

  19. Pösö AR, Wert JJ Jr, Mortimore GE (1982) Multifunctional control by amino acids of deprivation-induced proteolysis in liver. J Biol Chem 257: 12114–12120

    PubMed  Google Scholar 

  20. Pösö AR, Schworer CM, Mortimore GE (1982) Acceleration of proteolysis in perfused rat liver by deletion of glucogenic amino acids: Regulatory role of glutamine. Biochem Biophys Res Commun 107: 1433–1439

    Article  PubMed  Google Scholar 

  21. Peraino C, Harper AE (1963) Observations on protein digestion in vivo: Free amino acids in blood plasma of rats force-fed zein, casein, or their respective hydrolyzates. J Nutr 80: 270–278

    CAS  Google Scholar 

  22. Elwyn DH, Parikh HC, Shoemaker WC (1968) Amino acid movements between gut, liver and periphery in unanesthesized dogs. Am J Physiol 215: 1260–1275

    PubMed  CAS  Google Scholar 

  23. Khairallah EA, Mortimore GE (1976) Assessment of protein turnover in perfused rat liver. J Biol Chem 251: 1375–1384

    PubMed  CAS  Google Scholar 

  24. Mortimore GE, Woodside KH, Henry JE (1972) Compartmentation of free valine and its relation to protein turnover in perfused rat liver. J Biol Chem 247: 2776–2784

    PubMed  CAS  Google Scholar 

  25. Poole B, Wibo M (1973) Protein degradation in cultured cells. J Biol Chem 248: 6221–6226

    PubMed  CAS  Google Scholar 

  26. Epstein D, Elias-Bishko S, Hershko A (1975) Requirement for protein synthesis in the regulation of protein breakdown in cultured hepatoma cells. Biochemistry 14: 5199–5204

    Article  PubMed  CAS  Google Scholar 

  27. Hopgood MF, Clark MG, Ballard FJ (1977) Inhibition of protein degradation in isolated rat hepatocytes. Biochem J 164: 399–407

    PubMed  CAS  Google Scholar 

  28. Seglen PO, Gordon PB, Poli A (1980) Amino acid inhibition of the autophagic/lysosomal pathway of protein degradation in isolated rat hepatocytes. Biochim Biophys Acta 630: 103–118

    Article  PubMed  CAS  Google Scholar 

  29. Sommercora JM, Swick RW (1981) Protein degradation in primary monolayer cultures of adult rat hepatocytes. J Biol Chem 256: 4816–4821

    Google Scholar 

  30. De Duve C, Wattiaux R (1966) Functions of lysosomes. Annu Rev Physiol 28: 435–492

    Article  PubMed  Google Scholar 

  31. Ashford TP, Porter KR (1962) Cytoplasmic components in hepatic cell lysosomes. J Cell Biol 12: 198–202

    Article  PubMed  CAS  Google Scholar 

  32. Izzo JL, Glasser SR (1961) Comparative effects of glucagon, hydrocortisone, and epinephrine on the protein metabolism of the fasting rat. Endocrinology 68: 189–198

    Article  PubMed  CAS  Google Scholar 

  33. Miller LL (1960) Glucagon: A protein catabolic hormone in the isolated perfused rat liver. Nature (London) 185: 248

    Article  CAS  Google Scholar 

  34. Deter RL, De Duve C (1967) Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat lysosomes. J Cell Biol 33: 437–449

    Article  PubMed  CAS  Google Scholar 

  35. Neely AN, Nelson PB, Mortimore GE (1974) Osmotic alterations of the lysosomal system during rat liver perfusion: Reversible supression by insulin and amino acids. Biochim Biophys Acta 338: 458–472

    Article  CAS  Google Scholar 

  36. Mitchener JS, Shelburne JD, Bradford WD, Hawkins HK (1976) Cellular autophagocytosis induced by deprivation of serum and amino acids in HeLa cells. Am J Pathol 83: 485–498

    PubMed  CAS  Google Scholar 

  37. Mortimore GE, Schworer CM (1977) Induction of autophagy by amino acid deprivation in perfused rat liver. Nature (London) 270: 174–176

    Article  CAS  Google Scholar 

  38. Jefferson LS, Rannels DE, Munger BL, Morgan HE (1974) Insulin in the regulation of protein turnover in heart and skeletal muscle. Fed Proc 33: 1098–1104

    PubMed  CAS  Google Scholar 

  39. Arstila AU, Trump BF (1968) Studies on autophagocytosis: The formation of autophagic vacuoles in the liver following glucagon administration. Am J Pathol 53: 687–733

    PubMed  CAS  Google Scholar 

  40. Deter RL (1971) Quantitative characterization of dense body, autophagic vacuole, and acid phosphatase-bearing particle populations during the early phases of glucagon-induced autophagy in rat liver. J Cell Biol 48: 473–489

    Article  PubMed  CAS  Google Scholar 

  41. Pfeifer U (1978) Inhibition by insulin of the formation of autophagic vacuoles in rat liver. J Cell Biol 78: 152–167

    Article  PubMed  CAS  Google Scholar 

  42. Blouin A, Bolender RP, Weibel EW (1977) Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. J Cell Biol 72: 441–455

    Article  PubMed  CAS  Google Scholar 

  43. Knook DL, Sleyster EC (1980) Isolated parenchymal, Kupffer and endothelial rat liver cells characterized by their lysosomal enzyme content. Biochem Biophys Res Commun 96: 250–257

    Article  PubMed  CAS  Google Scholar 

  44. Munthe-Kaas AC, Berg T, Seljelid R (1976) Distribution of lysosomes in different types of rat liver cells. Exp Cell Res 99: 146–154

    Article  PubMed  CAS  Google Scholar 

  45. Pfeifer U (1973) Cellular autophagy and cell atrophy in the rat liver during long-term starvation. Virchows Arch AbtB Zellpathol 12: 195–211

    CAS  Google Scholar 

  46. Knowles SE, Ballard FJ (1976) Selective control of the degradation of normal and aberrant proteins in Reuber H35 hepatoma cells. Biochem J 156: 609–617

    PubMed  CAS  Google Scholar 

  47. Ward WF, Chua BL, Li JB, Morgan HE, Mortimore GE (1979) Inhibition of basal and deprivation-induced proteolysis by leupeptin and pepstatin in perfused rat liver and heart. Biochem Biophys Res Commun 87: 92–98

    Article  PubMed  CAS  Google Scholar 

  48. Dean RT (1975) Direct evidence of importance of lysosomes in degradation of intracellular proteins. Nature (London) 257: 414–416

    Article  CAS  Google Scholar 

  49. Fulks RM, Li JB, Goldberg AL (1975) Effects of insulin, glucose, and amino acids on protein turnover in rat diaphragm. J Biol Chem 250: 290–298

    PubMed  CAS  Google Scholar 

  50. Buse MG, Reid SS (1975) Leucine: A possible regulation of protein turnover in muscle. J Clin Invest 56: 1250–1261

    Article  PubMed  CAS  Google Scholar 

  51. Chua B, Siehl DL, Morgan HE (1979) Effect of leucine and metabolites of branched chain amino acids on protein turnover in heart. J Biol Chem 254: 8358–8362

    PubMed  CAS  Google Scholar 

  52. Grinde B, Seglen PO (1981) Leucine inhibition of autophagic vacuole formation in isolated rat hepatocytes. Exp Cell Res 134: 33–39

    Article  PubMed  CAS  Google Scholar 

  53. Shiman R, Mortimore GE, Schworer CM, Gray DW (1982) Regulation of phyenylalanine hydroxylase activity by phenylalanine in vivo, in vitro, and in perfused rat liver. J Biol Chem 257: 11213–11216

    PubMed  CAS  Google Scholar 

  54. Shiman R, Gray DW (1980) Substrate activation of phenylalanine hydroxylase. J Biol Chem 255: 4793–4800

    PubMed  CAS  Google Scholar 

  55. Chamalaun RAFM, Tager JM (1970) Nitrogen metabolism in the perfused rat liver. Biochim Biophys Acta 222: 119–134

    Article  PubMed  CAS  Google Scholar 

  56. Deaciuc IV, Petrescu I (1980) Regulation of glutamine catabolism in the perfused guinea-pig liver in relation to ureogenesis and gluconeogenesis. Int J Biochem 12: 605–618

    Article  PubMed  CAS  Google Scholar 

  57. Lund P (1980) Glutamine metabolism in the rat. FEBS Lett 117: K86–K92

    Article  PubMed  Google Scholar 

  58. Kovacevic Z, McGiven JD (1983) Mitochondrial metabolism of glutamine and glutamate and its physiological significance. Physiol Rev 63: 547–605

    PubMed  CAS  Google Scholar 

  59. Wanders RJA, Hoek JB, Tager JM (1980) Origin of the ammonia found in protein-free extracts of rat liver mitochondria and rat hepatocytes. Eur J Biochem 110: 197–202

    Article  PubMed  CAS  Google Scholar 

  60. Surmacz CA, Ward WF, Mortimore GE (1982) Distribution of 125I-Asialofetuin among liver particles separated on colloidal silica gradients. Biochem Biophys Res Commun 107: 1425–1432

    Article  PubMed  CAS  Google Scholar 

  61. Maxfield FR, Willingham MC, Davies PJA, Pastan I (1979) Amines inhibit the clustering of α2-macroglobulin and EGF on the fibroblast cell surface. Nature (London) 277: 661–663

    Article  CAS  Google Scholar 

  62. Sando G, Titus-Dillon P, Hall CW, Neufeld EF (1979) Inhibition of receptor-mediated uptake of a lysosomal enzyme into fibroblasts by chloroquine, procaine, and ammonia. Exp Cell Res 119: 359–364

    Article  PubMed  CAS  Google Scholar 

  63. Gordon AH, D’Arcy Hart P, Young MR (1980) Ammonia inhibits phagosome-lysosome fusion in macrophages. Nature (London) 286: 79–80

    Article  CAS  Google Scholar 

  64. Berg T, Tolleshaug H (1980) The effects of ammonium ions and chloroquine on uptake and degradation of 125I-labeled asialo-fetuin in isolated rat hepatocytes. Biochem Pharmacol 29: 917–925

    Article  PubMed  CAS  Google Scholar 

  65. Woodside KH, Ward WF, Mortimore GE (1974) Effects of glucagon on general protein degradation and synthesis in perfused rat liver. J Biol Chem 249: 5458–5463

    PubMed  CAS  Google Scholar 

  66. Hopgood MF, Clark MG, Ballard FJ (1980) Effects of glucagon, 3′:5′-cyclic monophosphate and insulin. Biochem J 186: 71–79

    PubMed  CAS  Google Scholar 

  67. Rosa F (1971) Ultrastructural changes produced by glucagon, cyclic 3′-5′AMP and epinephrine on perfused rat livers. J Ultrastruct Res 34: 205–213

    Article  PubMed  CAS  Google Scholar 

  68. Mallette LE, Exton JH, Park CR (1969) Effects of glucagon on amino acid transport and utilization in the perfused liver. J Biol Chem 244: 5724–5728

    PubMed  CAS  Google Scholar 

  69. Haussinger D (1983) Hepatocyte heterogeneity in glutamine and ammonia metabolism and the role of an intracellular glutamine cycle during ureogenesis in perfused rat liver. Eur J Biochem 133: 269–275

    Article  PubMed  CAS  Google Scholar 

  70. Joseph SK, McGiven JD (1978) The effect of ammonium chloride and glucagon on the metabolism of glutamine in isolated liver cells from starved rats. Biochim Biophys Acta 543: 16–28

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Physiology, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, PA, 17033, USA

    G. E. Mortimore

  2. Department of Biochemistry, College of Veterinary Medicine, Hämeentie 57, SF-0050, Helsinki 55, Finland

    A. R. Pösö

Authors
  1. G. E. Mortimore
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  2. A. R. Pösö
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Editor information

Editors and Affiliations

  1. Medizinische Universitätsklinik, Hugstetterstraße 55, 7800, Freiburg, Germany

    Dieter Häussinger

  2. Institut für Physiologische Chemie I, Universität Düsseldorf, Moorenstraβe 5, 4000, Düsseldorf, Germany

    Helmut Sies

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© 1984 Springer- Verlag Berlin Heidelberg

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Mortimore, G.E., Pösö, A.R. (1984). Mechanism and Control of Deprivation-Induced Protein Degradation in Liver: Role of Glucogenic Amino Acids. In: Häussinger, D., Sies, H. (eds) Glutamine Metabolism in Mammalian Tissues. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69754-8_9

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  • DOI: https://doi.org/10.1007/978-3-642-69754-8_9

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-69756-2

  • Online ISBN: 978-3-642-69754-8

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