Some Aspects of In Vivo Human Protein and Amino Acid Metabolism, with Particular Reference to Nutritional Modulation

  • V. R. Young
  • N. Fukagawa
  • D. M. Bier
  • D. Matthews
Conference paper


Under usual circumstances, the protein component of the diet serves as the source of amino acids which the body cannot make at a rate commensurate with meeting the metabolic needs of organs and tissues (the nutritionally indispensable or essential amino acids) and provides nitrogen for the synthesis of other amino acids (the nutritionally dispensable or non-essential amino acids) and nitrogen-containing compounds of physiologic and metabolic significance, such as neurotransmitters, creatinine, glutathione and nucleic acids. Where special nutritional therapies are necessary the amino acids and nitrogen can be supplied by formulations designed for either enteral or parenteral administration. In the body, proteins function as organic catalysts (enzymes), are used for the structural formation of cells, act as antibodies, and serve to control cellular metabolism (hormones and protein mediators). An inadequate protein or amino acid intake, due to lower than normal intakes or failure to raise intakes because of increased needs, causes diminished content of protein in cells and organs and deterioration in the capacity of cells to carry out their normal function. This leads to increased morbidity, and eventually death. Thus, an adequate diet, whether consisting of normal foods or specially formulated medical products, must contain an appropriate level of protein (nitrogen) and mixture of amino acids, in addition to major energy yielding substrates (carbohydrate and lipid) and other essential nutrients, including vitamins and minerals, if health is to be maintained and if the prevention of major body protein loss and/or restoration of body tissues during and following disease is to be achieved.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Jeejeeboy KN (1981) Protein nutrition in clinical practise. Brit Med Bull 37:11–17Google Scholar
  2. 2.
    Rennie MJ (1985) Muscle protein turnover and the wasting due to injury and disease. Brit Med Bull 41:257–264PubMedGoogle Scholar
  3. 3.
    Lewin B (1983) Genes. John Wiley & Sons, New York, pp 714Google Scholar
  4. 4.
    Ochoa S (1983) Regulation of protein synthesis initiation in eukaryotes. Arch Biochem Biophys 223:325–349PubMedCrossRefGoogle Scholar
  5. 5.
    Wold F (1981) In vivo chemical modification of proteins. Ann Rev Biochem 50:783PubMedCrossRefGoogle Scholar
  6. 6.
    Prockop DJ, Kivirikko KI, Yuderman L, Guzman NA (1979) The biosynthesis of collagen and its disorders. New Engl J Med 301:13–23, 77-85PubMedCrossRefGoogle Scholar
  7. 7.
    Campbell PN (1975) The biosynthesis of serum albumin. FEBS Lett 54:119–121PubMedCrossRefGoogle Scholar
  8. 8.
    Waterlow JC, Garlick PJ, Millward DJ (1978) Protein Turnover in Mammalian Tissues and in the Whole Body. North-Holland Publishing Co, Amsterdam, pp 804Google Scholar
  9. 9.
    Khairallah EA, Bond JS & Bird JWC (1985) (eds) Intracellular Protein Catabolism. Alan R Liss, New York pp 702Google Scholar
  10. 10.
    Rodeman HP, Goldberg AL (1982) Arachidonic acid, prostaglandin E2 and F2 influence rates of protein turnover in skeletal and cardiac muscle. J Biol Chem 257:1632–1638Google Scholar
  11. 11.
    Lund P, Williamson DH (1985) Inter-tissue nitrogen fluxes. Brit Med Bull 41:251–256PubMedGoogle Scholar
  12. 12.
    Waterlow JC (1984) Protein turnover with special reference to man. Quart Rev Exp Physiol 69:409–438Google Scholar
  13. 13.
    Bier DM, Matthews DE, Young VR (1985) Interpretation of whole body amino acid kinetic studies in the context of whole-body protein metabolism. In: Garrow JS, Halliday D (eds) Energy and Substrate Metabolism, John Libbey, London p 27–35Google Scholar
  14. 14.
    Bier DM, Young VR (1986) Assessment of whole body protein-nitrogen kinetics in the human infant. In: Proc Brystol-Myers Symposium, 1984 (in press)Google Scholar
  15. 15.
    Meguid MM, Matthews DE, Bier DM, Meredith CN, Soeldner JS, Young VR (1986) Leucine kinetics at graded leucine intakes in young men. Am J Clin Nutr 43:770–780PubMedGoogle Scholar
  16. 16.
    Zhao X-L, Wen Z-M, Meredith CN, Matthews DE, Bier DM, Young VR (1986) Threonine kinetics at graded threonine intakes in young men. Am J Clin Nutr 43:795–802PubMedGoogle Scholar
  17. 17.
    Meguid MM, Matthews DE, Bier DM, Meredith CN, Young VR (1986) Valine kinetics at graded valine intakes in young men. Am J Clin Nutr 43:781–786PubMedGoogle Scholar
  18. 18.
    Meredith CN, Wen Z-M, Bier DM, Matthews DE, Young VR (1986) Lysine kinetics at graded lysine intakes in young men. Am J Clin NutrGoogle Scholar
  19. 19.
    Matthews DE, Motil KJ, Rohrbaugh DK, Burke JF, Young VR, Bier DM (1980) Measurement of leucine metabolism in man from a primed, continuous infusion of L-[1-13C]leucine. Am J Physiol 238:E473–E479PubMedGoogle Scholar
  20. 20.
    Picou D, Taylor-Roberts T (1969) The measurement of total protein synthesis and catabolism and nitrogen turnover in infants in different nutritional states and receiving different amounts of dietary protein. Clin Sci 36:283–296PubMedGoogle Scholar
  21. 21.
    Waterlow JC, Golden MHN, Garlick PJ (1978) Protein turnover in man measured ith 15N: comparison of end products and dose regimes. Am J Physiol 235:E165–E174PubMedGoogle Scholar
  22. 22.
    Garlick PJ (1980) Protein turnover in the whole animal and specific tissues. In: Florkin M, Stolz E, Neuberger A (eds) Comprehensive Biochemistry. Elsevier, Amsterdam, pp 77–152Google Scholar
  23. 23.
    Fern EB, Garlick PJ, McNurlan MA, Waterlow JC (1981) The excretion of isotope in urea and ammonia for estimating protein turnover in man with 15N glycine. Clin Sci 61:217–228PubMedGoogle Scholar
  24. 24.
    Fern EB, Garlick PJ, Waterlow JC (1985) The concept of the single body pool of metabolic nitrogen in determining the rate of whole-body nitrogen turnover. Human Nutrition: Clinical Nutrition 39C:85–99Google Scholar
  25. 25.
    Matthews DE, Conway JM, Young VR, Bier DM (1981) Glycine nitrogen metabolism in man. Metabolism 30:886–893PubMedCrossRefGoogle Scholar
  26. 26.
    Jackson AA, Golden MHN (1980) [15N]glycine metabolism in normal man: the metabolic α-amino nitrogen pool. Clin Sci 58:517–522PubMedGoogle Scholar
  27. 27.
    Catefils C, Schutz Y, Micheli J-L, Welsch C, Arnaud MJ, Jequier E (1985) Whole body protein synthesis and energy expenditure in very low birth weight infants. Pediatrie Res 19:679–687Google Scholar
  28. 28.
    Waterlow JC (1981) 15N end-product methods for study of whole body protein turnover. Proc Nutr Soc 40:317–320PubMedCrossRefGoogle Scholar
  29. 29.
    Steffee WP, Goldsmith RS, Pencharz PB, Scrimshaw NS, Young VR (1976) Dietary protein intake and dynamic aspects of whole body nitrogen metabolism in adult humans. Metabolism 25:281–297PubMedCrossRefGoogle Scholar
  30. 30.
    Waterlow JC, Stephen JML (1967) The measurement of total lysine turnover in the rat by intravenous infusion of L-[U-14C] lysine. Clin Sci 33:489–503PubMedGoogle Scholar
  31. 31.
    Waterlow JC (1967) Lysine turnover in man measured by intravenous infusion of L-[U-14C]lysine. Clin Sci 33:507–515PubMedGoogle Scholar
  32. 32.
    James WPT, Garlick PJ, Sender PM, Waterlow JC (1976) Studies of amino acid and protein metabolism in normal man with L-[U-14C]tyrosine. Clin Sci Mol Med 50:525–532PubMedGoogle Scholar
  33. 33.
    Matthews DE, Schwarz HP, Yang RD, Motil KJ, Lyoung VR, Bier DM (1982) Relationship of plasma leucine and α-ketoisocaproate during a L-[1-13C]leucine infusion in man: A method for measuring human intracellular tracer enrichment. Metabolism 31:1105–1112PubMedCrossRefGoogle Scholar
  34. 34.
    Hoerr RA, Matthews DE, Bier DM, Blackburn GL, Young VR (1984) Splanchnic bed metabolism of leucine in man measured by simultaneous intravenous and intragastric infusion of stable isotope tracers of leucine. Am J Clin Nutr 36:687 (abstract)Google Scholar
  35. 35.
    Abumrad NN, Rabin D, Diamond MP, Lacy WW (1981) Use of a heated superficial hand vein as an alternative for the measurement of amino acid concentrations and for the study of glucose and amino acid kinetics in man. Metabolism 30:936–940PubMedCrossRefGoogle Scholar
  36. 36.
    Darmaun D, Matthews DE, Bier DM (1984) Glutamine and glutamate nitrogen metabolism in man. Clin Res 32:627AGoogle Scholar
  37. 37.
    Chaisson JL, Lilenquist JE, Sinclair-Smith BC, Lacy WW (1975) Gluconeogenesis from alanine in post-absorptive man. Diabetes 24:574–584CrossRefGoogle Scholar
  38. 38.
    O’Keefe SJC, Davis M, Williams R (1982) Evidence for in vivo compartmentation of amino acids between blood cells and plasma in man with liver disease during constant infusion of L[U-14C]tyrosine. Metabolism 31:701–703PubMedCrossRefGoogle Scholar
  39. 39.
    Hoffer LJ, Yang RD, Matthews DG, Bistrian BR, Bier DM, Young VR (1985) Effects of meal consumption on whole body leucine and alanine kinetics in young men. Brit J Nutr 53:31–38PubMedCrossRefGoogle Scholar
  40. 40.
    Pell JM, Caldarone EM, Bergman EN (1983) Importance of sites of tracer administration and blood sampling in relation to leucine metabolism. Biochem J 214:1015PubMedGoogle Scholar
  41. 41.
    Matthews DE, Bier DM, Rennie MJ, Edwards RHT, Holliday D, Millward DJ, Clugston GA (1981) Regulation of leucine metabolism in man: A stable isotope study. Science 214:1129–1131PubMedCrossRefGoogle Scholar
  42. 42.
    Yang RD, Matthews DE, Bier DM, Lo C, Young VR (1984) Alanine kinetics in humans: Influence of different isotopic tracers. Am J Physiol 247:E634–E638PubMedGoogle Scholar
  43. 43.
    Young VR, Meredith C, Hoerr R, Bier DM, Matthews DE (1985) Amino acid kinetics in relation to protein and amino acid requirements: The primary importance of amino acid oxidation. In: Garrow JS, Dolliday D (eds) Substrate and Energy Metabolism. John Libbey, London, pp 119–133Google Scholar
  44. 44.
    Pencharz PB, Musson M, Desgranges F, Papageorgiou A (1981) Total body protein turnover in human premature neonates: effects of birth weight, intrauterine nutritional status and diet. Clin Sci 61:201–215Google Scholar
  45. 45.
    FAO/WHO/UNO (1985) Energy and Protein Requirements. WHO Tech Rept Ser No 724. WHO, GenevaGoogle Scholar
  46. 46.
    Young VR, Steffee WP, Pencharz PB, Winterer JC, Scrimshaw NS (1975) Total human body protein synthesis in relation to protein requirements at various ages. Nature 253:192–194PubMedCrossRefGoogle Scholar
  47. 47.
    Munro HW (1969) Evolution of protein metabolism: In: Munro HN (ed) Mammalian Protein Metabolism, Vol. III. Academic Press, New York, pp 133–182Google Scholar
  48. 48.
    Waterlow JC (1968) Observations on the mechanisms of adaptation to low protein intakes. Lancet ii: 1091–1097CrossRefGoogle Scholar
  49. 49.
    Brody S (1945) Bioenergetics and growth. Reinhold Publishers, New YorkGoogle Scholar
  50. 50.
    Kleiber M (1961) The Fire of Life. J. Wiley and Sons, New YorkGoogle Scholar
  51. 51.
    Kien CL, Young VR, Rohrbaugh DK, Burke JF (1978) Increased rates of whole body protein synthesis and breakdown in children recovering from burns. Ann Surgery 187:383–391CrossRefGoogle Scholar
  52. 52.
    Kien CL, Rohrbaugh DK, Burke JF, Young VR (1978) Whole body protein synthesis in relation to basal energy expenditure in healthy children and in children recovering from burn injury. Pediat Res 12:211–216PubMedGoogle Scholar
  53. 53.
    Bilmazes C, Kien CL, Rohrbaugh DK, Uauy R, Burke JF, Munro HN, Young VR (1978) Quantitative contribution by skeletal muscle to elevated rates of whole body protein breakdown in burned children, as measured by Nr-methylhistidine output. Metabol 27:671–676CrossRefGoogle Scholar
  54. 54.
    Shock NW (1972) Energy metabolism, caloric intake and physical activity of the aging. In: Carlson Nutrition in old age. X Symposium of the Swedish Nutrition Foundation. Swedish Nutrition Foundation, Uppsala, pp 12–23Google Scholar
  55. 55.
    Tzankoff SP, Norris AH (1979) Effect of muscle mass decrease on age-related BMR changes. J Appl Physiol 43:1001–1006Google Scholar
  56. 56.
    Uauy R, Winterer JC, Bilmazes C, Haverberg LN, Scrimshaw NS, Munro HN, Young VR (1978) The changing patterns of whole body protein metabolism in aging humans. J Gerontol 33:663–671PubMedGoogle Scholar
  57. 57.
    Wayler A, Quieroz E, Scrimshaw NS, Steinke FH, Rand WM, Young VR (1983) Nitrogen balance studies in young men to assess the protein quality of an isolated soy protein in relation to meat proteins. J Nutr 113:2485–2491PubMedGoogle Scholar
  58. 58.
    Sim AJ, Wolfe BM, Young VR, Clarke D, Moore FD (1979) Glucose promotes whole body synthesis from infused amino acids in fasting man. Lancet i:68–72CrossRefGoogle Scholar
  59. 59.
    Golden MHN, Waterlow JC, Picou D (1977) Protein turnover, synthesis and breakdown before and after recovery from protein-energy malnutrition. Clin Sci and Molecular Med 53:473–477Google Scholar
  60. 60.
    Golden MHN, Waterlow JC, Picou D (1977) The relationship between dietary intake, weight change, nitrogen balance, and protein turnover in man. Am J Clin Nutr 30:1345–1348PubMedGoogle Scholar
  61. 61.
    Young VR (1981) Dynamics of human whole body amino acid metabolism: Use of stable isotope probes and relevance to nutritonal requirements. J Nutr Sci Vitaminology 27:395–413CrossRefGoogle Scholar
  62. 62.
    Young VR, Yang RD, Meredith C, Matthews DE, Bier DM (1983) Modulation of amino acid metabolism by protein and energy intakes. In: Blackburn GL, Grant JP, Young VR (eds) Amino Acids Metabolism and Medical Applications. John Wright PSG, Littleton, Chapter 2, pp 13–28Google Scholar
  63. 63.
    Reeds PJ, Fuller MF (1983) Nutrient intake and protein turnover. Proc Nutr Soc 42:463–471PubMedCrossRefGoogle Scholar
  64. 64.
    Millward DJ (1979) Protein deficiency, starvation and protein metabolism. Proc Nutr Soc 38:77–88PubMedCrossRefGoogle Scholar
  65. 65.
    Waterlow JC, Stephen JML (eds) (1981) Nitrogen Metabolism in Man. Applied Science Publishers, London, pp 558Google Scholar
  66. 66.
    Harper AE, Benjamin E (1984) Relationship between intake and rate of oxidation of leucine and α-ketoisocaproate in vivo in the rat. J Nutr 114:431–440PubMedGoogle Scholar
  67. 67.
    Harper AE (1983) Some recent developments in the study of amino acid metabolism. Proc Nutr Soc 42:437–449PubMedCrossRefGoogle Scholar
  68. 68.
    Brookes JM, Owens FN, Garrigus VS (1972) Influence of amino acid level in the diet upon amino acid oxidation by the rat. J Nutr 102:27–36PubMedGoogle Scholar
  69. 69.
    Ishibashi T, Kametaka M (1977) Lysine requirement of rats of various body weights. Agr Biol Chem 41:1727–1732CrossRefGoogle Scholar
  70. 70.
    Bergner H, Simon O, Adam K (1978) Estimation of lysine requirement in growing rats from rate of catabolism of 14C-and 15N-labelled lysine. Archiv für Tierernährung 28:21–29PubMedCrossRefGoogle Scholar
  71. 71.
    Simon O, Adam K, Bergner H (1978) Stofrwechselorientierte Lysin-bedarfsbestimmung bei ausgewachsenen Ratten anhand der Katabolisierungsrate von 14C-und 15N-markiertem Lysin. Arch Tierernährung 28:609CrossRefGoogle Scholar
  72. 72.
    Kang-Lee TA, Harper AE (1977) Effect of histidine intake and hepatic histidase activity on the metabolism of histidine in vivo. J Nutr 107:1427–1443PubMedGoogle Scholar
  73. 73.
    Kang-Lee TA, Harper AE (1978) Threonine metabolism in vivo effect of threonine intake and prior induction of threonine dehydration in rats. J Nutr 108:168–175Google Scholar
  74. 74.
    Kim K-I, McMillan J, Bayley HS (1983) Determination of amino acid requirements in young pigs using an indicator amino acid. Brit J Nutr 50:369–382PubMedCrossRefGoogle Scholar
  75. 75.
    Kim K-I, Bayley HS (1983) Amino acid oxidation by young pigs receiving diets with varying levels of sulphur amino acids. Brit J Nutr 50:383–390PubMedCrossRefGoogle Scholar
  76. 76.
    Kim K-I, Elliott J, Bayley HS (1983) Oxidation of an indicator amino acid by young pigs receiving diets with varying levels of lysine or threonine, and an assessment of amino acid requirements. Brit J Nutr 50:391–399PubMedCrossRefGoogle Scholar
  77. 77.
    Young VR, Moldawer LL, Hoerr R, Bier DM (1984) Mechanisms of adaptation to protein malnutrition. In: Blaxter KL, Waterlow JC (eds) Nutritional Adaptation in Man. John Libbey & Sons, LondonGoogle Scholar
  78. 78.
    Munro HN (1972) Amino acid requirements and metabolism and their relevance to parenteral nutrition. In: Wilkinson AW (ed) Parenteral Nutrition. Churchill Livingston, Edinburgh, pp 34–67Google Scholar
  79. 79.
    Rose WC (1957) The amino acid requirements of adult man. Nutr Abstr Rev 27:631–647Google Scholar
  80. 80.
    Young VR, Meguid M, Meridith C, Matthews D, Bier DM (1981) Recent developments in knowledge of human amino acid requirements. In: Waterlow JC, Stephen JML (eds) Nitrogen Metabolism in Man. Applied Science Publishers, London, pp 133–153Google Scholar
  81. 81.
    Meredith C, Bier DM, Meguid MM, Matthews DE, Wen Z, Young VR (1982) Whole body amino acid turnover with 13C tracers: A new approach for estimation of human amino acid requirements. In: Wesdorp RIC, Soeters PB (eds) Clinical Nutrition’ 81. Churchill Livingstone, London New York, pp 42–59Google Scholar
  82. 82.
    Waterlow JC (1985) What do we mean by adaptation? In: Blaxter Sir K, Waterlow JC (eds) Nutritional Adaptation in Man. J Libbey, London, pp 1–10Google Scholar
  83. 83.
    Hegsted DM (1976) Balance Studies J Nutr 106:307–311Google Scholar
  84. 84.
    Young VR (1986) Nutritional balance studies: Indicators of human requirements or of adaptive mechanisms? J Nutr 116 (in press)Google Scholar
  85. 85.
    Rigo J, Senterre J (1982) Amino acid requirements in preterm infants on oral or parenteral nutrition. In: Wesdorp RIC, Soeters PB (eds) Clinical Nutrition ‘81. Churchill Livingstone, London, pp 71–77Google Scholar
  86. 86.
    Ming Yu Y, Yang RD, Matthews DE, Burke JF, Bier DM, Young VR (1985) Quantitative aspects of glycine and alanine nitrogen metabolism in young men: Effect of level of nitrogen and dispensable amino acid intake. J Nutr 115:399–410Google Scholar
  87. 87.
    Robert J-J, Bier DM, Zhao XH, Matthews DE, Young VR (1982) Glucose and insulin effects on de novo amino acid synthesis in young men: Studies with stable isotope labeled alanine, glycine, leucine and lysine. Metab 31:1210–1218CrossRefGoogle Scholar
  88. 88.
    Young VR, Bier DM (1981) Protein metabolism and nutritional state in man. Proc Nutr Soc 40:343–359PubMedCrossRefGoogle Scholar
  89. 89.
    Yang RD, Matthews DE, Bier DM, Wen AM, Young VR (1986) Response of alanine metabolism in humans to manipulation of dietary protein and energy intakes. Am J Physiol 250:E39–E46PubMedGoogle Scholar
  90. 90.
    Ladato RF, Smith RJ, Valle D, Phang JM, Aoki TT (1981) The regulation of proline biosynthesis: The inhibition of pyroline-5-carboxylate synthase activity by ornithine. Metabolism 30:908–913CrossRefGoogle Scholar
  91. 91.
    Munro HN, Crim, MC (1981) The proteins and amino acids. In: Goodhart RS, Shils ME (eds) Modern Nutrition in Health and Disease. 6th edn Lea and Febiger, Philadelphia, pp 51–98Google Scholar

Copyright information

© J. F. Bergmann Verlag, München 1988

Authors and Affiliations

  • V. R. Young
    • 1
    • 2
  • N. Fukagawa
    • 1
    • 2
  • D. M. Bier
    • 1
    • 2
  • D. Matthews
    • 1
    • 2
  1. 1.Department of Applied Biological Sciences and Clinical ResearchCenter Massachusetts Institute of TechnologyCambridgeUK
  2. 2.Departments of Medicine and Pediatrics WashingtonUniversity School of MedicineSt. LouisUSA

Personalised recommendations