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Isotopes in nutrition research

Published online by Cambridge University Press:  28 February 2007

Vernon R. Young*
Affiliation:
Laboratory of Human Nutrition, School of Science and Clinical Research Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Alfred Ajami
Affiliation:
MassTrace Inc., Woburn, MA 01801, USA
*
*Corresponding author: Dr Vernon R. Young, fax +1 617 253 9658, email [email protected]
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Abstract

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The present lecture begins with a brief overview of the professional and scientific journey taken by Rudolf Schoenheimer, before turning to a discussion of the power of isotopic tracers in nutrition research. Schoenheimer's remarkable contributions to the study of intermediary metabolism and the turnover of body constituents, based initially on compounds tagged with 2H and later with 15N, spanned a mere decade. It is difficult, however, to overestimate the enormous impact of Schoenheimer's research on the evolution of biological science. After a relative hiatus, following Schoenheimer's death in 1941, in the use of stable nuclides as tracers in metabolism and nutrition, especially in human subjects, there is now an expanded and exciting range of techniques, experimental protocols and stable-isotope tracer compounds that are helping to probe the dynamic aspects of the metabolism of the major energy-yielding substrates, amino acids and other N-containing compounds, vitamins and mineral elements in human subjects. Various aspects of the contemporary applications of these tracers in nutrition research are covered in the present lecture.

Type
The Rudolf Schoenheimer Centenary Lecture
Copyright
Copyright © The Nutrition Society 1999

References

Abrams, SA (1994) Clinical studies of mineral metabolism in children using stable isotopes. Journal of Pediatric Gastroenterology and Nutrition 19, 151163.Google ScholarPubMed
Aggett, PJ (1997) Iron, copper and zinc absorption and turnover; the use of stable isotopes. European Journal of Pediatrics 156, S29S34.CrossRefGoogle ScholarPubMed
Arquint, P, Kovdelka-Hep, M, van der Schoot, BH, van der Wal, P & de Rooij, NF (1994) Micromachined analyzers on a silicon chip. Clinical Chemistry 40, 18051809.CrossRefGoogle ScholarPubMed
Ballmer, PE, McNurlan, MA, Essen, P, Anderson, SE & Garlick, PJ (1995 a) Albumin synthesis rates measured with [2H5-ring]phenylalanine are not responsive to short-term intravenous nutrients in healthy humans. Journal of Nutrition 125, 512519.Google Scholar
Ballmer, PE, McNurlan, MA, Hulter, HN, Anderson, SE, Garlick, PJ & Krapf, R (1995 b) Chronic metabolic acidosis decreases albumin synthesis and induces negative nitrogen balance in humans. Journal of Clinical Investigation 95, 3945.CrossRefGoogle ScholarPubMed
Berthold, HK, Hachey, DL, Reeds, PJ, Thomas, OP, Hoeksema, S & Klein, PD (1991) Uniformly 13C-labeled algae protein used to determine amino acid essentiality in vivo. Proceedings of the National Academy of Sciences USA 88, 80918095.CrossRefGoogle Scholar
Berthold, HK, Jahoor, F, Klein, PD & Reeds, PR (1995 a) Estimates of the effect of feeding on whole-body protein degradation in women vary with the amino acid used as tracer. Journal of Nutrition 125, 25162527.Google ScholarPubMed
Berthold, HK & Klein, PD (1991) Zum 50 Todestag von Rudolf Schoenheimer. Er revolutionerte die Kenntnisse vom Stoffwechsel (On the 50th anniversary of Rudolf Schoenheimer's death. He revolutionized the knowledge of metabolism). Deutsches Arzteblatt-Arztliche Mitteilungen 68, 30583060.Google Scholar
Berthold, HK, Reeds, PJ & Klein, PD (1995 b) Isotopic evidence for the differential regulation of arginine and proline synthesis in man. Metabolism 44, 466473.CrossRefGoogle ScholarPubMed
Beylot, M (1994) The use of stable isotopes and mass spectrometry in studying lipid metabolism. Proceedings of the Nutrition Society 53, 355362.CrossRefGoogle ScholarPubMed
Bier, DM (1981) Intrinsically difficult problems: the kinetics of body proteins and amino acids in man. Diabetes/Metabolism Reviews 5, 111132.CrossRefGoogle Scholar
Bier, DM (1987) The use of stable isotopes in metabolic investigation. Ballière's Clinical Endocrinology and Metabolism 1, 817836.CrossRefGoogle ScholarPubMed
Bier, DM (1997) Stable isotopes in biosciences, their measurement and models of amino acid metabolism. European Journal of Pediatrics 156, S2S8.CrossRefGoogle ScholarPubMed
Biolo, G, Flemming, RY, Moggi, SP & Wolfe, RR (1995) Transmembrane transport and intracellular kinetics of amino acids in human skeletal muscle. American Journal of Physiology 268, E75E84.Google ScholarPubMed
Bloom, FE (1997) Breakthroughs 1997. Science 278, 2029.CrossRefGoogle ScholarPubMed
Boutton, TW, Lynott, MJ & Bumsted, MP (1991) Stable carbon isotopes and the study of prehistoric human diet. Critical Reviews in Food Science and Nutrition 30, 373385.CrossRefGoogle Scholar
Brunengraber, H, Kelleher, JK & des Rosiers, C (1997) Applications of mass isotomer analysis to nutrition research. Annual Reviews of Nutrition 17, 559596.CrossRefGoogle ScholarPubMed
Buckley, WT (1988) The use of stable isotopes in studies of mineral metabolism. Proceedings of the Nutrition Society 47, 407416.CrossRefGoogle ScholarPubMed
Bustany, P, Chatel, M, Derlon, JM, Sgouropoulos, P, Soussaline, F & Syrota, A (1986) Brain tumor protein synthesis and histological grades; a study by positron emission tomography (PET) with C-11-l-methionine. Journal of Neuro-oncology 3, 397404.CrossRefGoogle Scholar
Castillo, L, Beaumier, L, Ajami, AM & Young, VR (1996) Whole body nitric oxide synthesis in healthy men determined from [15N]arginine-to-[15N]citrulline labeling. Proceedings of the National Academy of Sciences USA 93, 1146011465.CrossRefGoogle Scholar
Castillo, L, Chapman, TE, Sànchez, M, Yu, Y-M, Burke, JF, Ajami, AM, Vogt, J & Young, VR (1993) Plasma arginine and citrulline kinetics in adults given adequate and arginine-free diets. Proceedings of the National Academy of Sciences USA 90, 77497753.CrossRefGoogle ScholarPubMed
Chan, P & Abramson, FP (1998) Measuring DNA synthesis with [1-13C]glycine. Analytical Chemistry 70, 16641669.CrossRefGoogle Scholar
Christian, PE (1994) Physics of nuclear medicine. In Nuclear Medicine. Technology and Techniques, 3rd ed., pp.3552 [Bernier, DR, Christian, PE and Langan, JK, editors]. St Louis, MO: Mosby.Google Scholar
Chugani, HT, Phelps, ME & Mazziotta, JC (1987) Positron emission tomography study of human brain functional development. Annals of Neurology 22, 487497.CrossRefGoogle ScholarPubMed
Ciechanover, A & Schwartz, AL (1998) The ubiquitin-proteasome pathway: the complexity and myriad functions of proteins death. Proceedings of the National Academy of Sciences USA 95, 27272730.CrossRefGoogle ScholarPubMed
Clifford, AA & Müller, H-G (editors) (1998) Mathematical modeling in experimental nutrition New York: Plenum Press.CrossRefGoogle Scholar
Cline, GW, Jucker, BM, Trajanoski, Z, Rennings, AJM & Shulman, GI (1998) A novel 13C NMR method to assess intracellular glucose concentration in muscle, in vivo. American Journal of Physiology 274, E381E389.Google ScholarPubMed
Cobelli, C, Bier, DM & Ferannini, E (1990) Modelling glucose metabolism: theory and practice. Hormone and Metabolic Research 24, Suppl., 110.Google ScholarPubMed
Cobelli, C & Caumo, A (1998) Using what is accessible to that which is not: necessity of model of systems. Metabolism 47, 10091035.CrossRefGoogle ScholarPubMed
Cobelli, C, Saccomoni, MP, Tessari, P, Biolo, G, Luzi, L & Matthews, DE (1991) Compartmental model of leucine kinetics in humans. American Journal of Physiology 261, E539E550.Google ScholarPubMed
Cobelli, C, Toffolo, G, Bier, DM & Nosadini, R (1987) Models to interpret kinetic data in stable isotope tracer studies. American Journal of Physiology 253, E551E564.Google ScholarPubMed
Coburn, SP & Townsend, DW (editors) (1996) Mathematical modeling in experimental nutrition: vitamins, proteins, methods. Advances in Food and Nutrition Research 40, 1362.Google Scholar
Cohn, M (1995) Some early tracer experiments with stable isotopes. Protein Science 4, 24442447.CrossRefGoogle ScholarPubMed
Crews, HM, Ducros, V, Eagles, J, Mellon, FA, Kastenmayer, P, Luten, JB & McGaw, BA (1994) Mass spectrometric methods for studying nutrient mineral and trace element absorption and metabolism in humans using stable isotopes. A review. Analyst 119, 24912514.CrossRefGoogle ScholarPubMed
Daghighian, F, Sumida, R & Phelps, ME (1990) PET imaging: an overview and instrumentation. Journal of Nuclear Medicine Techniques 18, 515.Google Scholar
Demmelmair, H, Sauerwold, T, Koletzko, B & Richter, T (1997) New insights into lipid and fatty acid metabolism via stable isotopes. European Journal of Pediatrics 156, S70S74.CrossRefGoogle ScholarPubMed
Drexler, HCA (1997) Activation of the cell death program by inhibition of proteasome function. Proceedings of the National Academy of Sciences USA 94, 855860.CrossRefGoogle ScholarPubMed
Dudley, MA, Burren, DG, Wykes, LJ, Toffolo, G, Cobelli, C, Nichols, BL, Rosenberger, J, Jahoor, F & Reeds, PJ (1998) Protein kinetics determined in vivo with a multi-tracer, single-sample protocol: application to lactase synthesis. American Journal of Physiology 274, G591G598.Google Scholar
Effenhauser, CS & Manz, A (1994) Miniaturizing a whole analytical laboratory down to chip size. American Laboratory September 15–18.Google Scholar
El-Khoury, AE, Fukagawa, NK, Sànchez, M, Tsay, RH, Gleason, RE, Chapman, TE & Young, VR (1994) Validation of the tracer-balance concept with reference to leucine: 24-h intravenous tracer studies with l-[1-13C]leucine and [15N-15N]urea. American Journal of Clinical Nutrition 59, 10001011.CrossRefGoogle Scholar
Evans, JE, Browne, TR, Kasdon, DL, Szabo, GK, Evans, BA & Greenblatt, DJ (1985) Staggered stable isotope technique for study of drug distribution. Journal of Clinical Pharmacology 25, 309312.CrossRefGoogle ScholarPubMed
Fischman, AJ, Yu, Y-M, Livini, E, Bobech, JW, Young, VR, Alpert, NM & Tompkins, RG (1998) Muscle protein synthesis by positron emission tomography with l-[methyl-11C]methionine in adult humans. Proceedings of the National Academy of Sciences USA 95, 1279312798.CrossRefGoogle Scholar
Fitzpatrick, SM, Hetherington, HP, Behar, KL & Shulman, RG (1990) The flux from glucose to glutamate in the rat brain in vivo as determined by 2H-observed, 13C-edited NMR spectroscopy. Journal of Cerebral Blood Flow and Metabolism 10, 170179.CrossRefGoogle ScholarPubMed
Flatt, JP (1995) McCollum award lecture 1995: Diet, lifestyle and weight maintenance. American Journal of Clinical Nutrition 62, 820836.CrossRefGoogle ScholarPubMed
Folin, O (1905) A theory of protein metabolism. American Journal of Physiology 13, 117138.CrossRefGoogle Scholar
Fowler, JS & Wolf, AP (1986) Positron emitter-labeled compounds: priorities and problems. In Positron Emission Tomography and Autoradiography. Principles and Applications for the Brain, pp. 391450 [Phelps, ME, Mazziotta, TC and Schelbert, HR, editors]. New York: Raven Press.Google Scholar
Fukagawa, N, Yu, Y-M & Young, VR (1998) Methionine-cysteine kinetics at different intakes of methionine and cystine in elderly men and women. American Journal of Clinical Nutrition (In the Press).CrossRefGoogle ScholarPubMed
Garlick, PJ & Millward, DJ (1972) An appraisal of techniques for the determination of protein turnover in vivo. Proceedings of the Nutrition Society 31, 249255.CrossRefGoogle ScholarPubMed
Ghislain, M, Udvardy, A & Mann, C (1993) S. cerevisiae 26S protease mutants arrest cell division in G2/metaphase. Nature 366, 358362.CrossRefGoogle Scholar
Grindstaff, PD, Kreider, R, Bishop, R, Wilson, M, Wood, L, Alexander, C & Almada, A (1997) Effects of creatine supplementation on respective sprint performance and body composition in competitive swimmers. International Journal of Sports Nutrition 7, 330346.CrossRefGoogle Scholar
Hadd, AG, Raymond, DE, Halliwell, JW, Jacobson, SC & Ramsey, JM (1997) Microchip device for performing enzyme assays. Analytical Chemistry 69, 34073412.CrossRefGoogle ScholarPubMed
Halliday, D & Read, WW (1981) Mass spectrometric assay of stable isotopic enrichment for the estimation of protein turnover in man. Proceedings of the Nutrition Society 40, 321324.CrossRefGoogle ScholarPubMed
Halliday, D & Rennie, MJ (1982) The use of stable isotopes for diagnosis and clinical research. Clinical Science 63, 485496.CrossRefGoogle ScholarPubMed
Harding, CV, France, J, Song, R, Farah, JM, Chatterjee, S, Igbal, M & Siman, R (1995) Novel dipeptide aldehydes are proteasome inhibitors and block the MHC-1 antigen-processing pathway. Journal of Immunology 155, 17671775.CrossRefGoogle Scholar
Hawkins, RA, Huang, S-C, Barrio, JR, Keen, RE, Feng, D, Massiotta, JC & Phelps, ME (1989) Estimation of local cerebral protein synthesis rates with 1-[1-11C]leucine and PET: Methods, modal and results in animals and humans. Journal of Cerebral Blood Flow and Metabolism 9, 446460.CrossRefGoogle Scholar
Hellerstein, MK & Neese, RA (1992) Mass isotomer distribution analysis: A technique for measuring biosynthesis and turnover of polymers. American Journal of Physiology 263, E998E1001.Google ScholarPubMed
Hellerstein, MK, Neese, RA, Linfort, P, Christiansen, M, Turner, S & Letscher, A (1997) Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans: a stable isotope study. Journal of Clinical Investigation 100, 13051319.CrossRefGoogle ScholarPubMed
Hellerstein, MK, Schwarz, JM & Neese, R (1996) Regulation of hepatic de novo lipogenesis in humans. Annual Reviews of Nutrition 16, 523527.CrossRefGoogle ScholarPubMed
Hevesey, G (1923) The absorption and translocation of lead by plants. Biochemical Journal 17, 439445.CrossRefGoogle Scholar
Hoffman, EJ & Phelps, ME (1986) Positron emission tomography: Principles and quantitation. In Positron Emission Tomography and Autoradiography. Principles and Applications for the Brain, pp. 237286 [Phelps, ME, Mazziotta, TC and Schelbert, HR, editors]. New York: Raven Press.Google Scholar
Hovorka, R, Eckland, DJA, Halliday, D, Lettis, S, Robinson, C, Bannister, P, Young, MA & Bye, A (1997) Constant infusion and bolus injection of stable-label tracer given reproducible and comparable fasting HGO. American Journal of Physiology 273, E192E201.Google Scholar
Hsieh, S & Jorgensen, JW (1997) Determination of enzyme activity in single bovine adrenal medullary cells by separation of isotopically labeled catecholamines. Analytical Chemistry 69, 39073914.CrossRefGoogle ScholarPubMed
Hsu, H, Yu, YM, Babich, JW, Burke, JF, Livini, E, Tompkins, RG, Young, VR, Alpert, NM & Fischman, AJ (1996) Measurement of muscle protein synthesis by positron emission tomography with l-[methyl-11C]methionine. Proceedings of the National Academy of Sciences USA 93, 18411846.CrossRefGoogle Scholar
Huang, SC, Carson, RE, Hoffman, EJ, Carson, J, MacDonald, N, Barrio, JR & Phelps, ME (1983) Quantitative measurement of local cerebral blood flow in humans by positron computed tomography and O-15 water. Journal of Cerebral Blood Flow and Metabolism 3, 141153.CrossRefGoogle Scholar
Huang, SC, Feng, DG & Phelps, ME (1986) Model dependency and estimation reliability in measurement of cerebral oxygen utilization rate with oxygen-15 and dynamic positron emission tomography. Journal of Cerebral Blood Flow and Metabolism 6, 105119.CrossRefGoogle ScholarPubMed
Huang, SC & Phelps, ME (1986) Principles of tracer kinetic modeling in positron emission tomography and autoradiography. In Positron Emission Tomography and Autoradiography. Principles and Applications for the Brain, pp. 287346 [Phelps, ME, Mazziotta, TC and Schelbert, HR, editors]. New York: Raven Press.Google Scholar
Irving, CS, Thomas, MR, Malphus, EW, Marks, L, Wong, WW, Boutton, TW & Klein, PD (1986) Lysine metabolism and protein metabolism in young women. Journal of Clinical Investigation 77, 13211331.CrossRefGoogle ScholarPubMed
Jackson, AA (1991) The glycine story. European Journal of Clinical Nutrition 45, 5965.Google ScholarPubMed
Janghorbani, M (1984) Stable isotopes in nutrition and food science. Progress in Food and Nutrition Science 8, 303332.Google ScholarPubMed
Janghorbani, M & Young, VR (1982) Advances in the use of stable isotopes in minerals in human studies. Federation Proceedings 41, 27022708.Google ScholarPubMed
Kaehler, T (1994) Nanotechnology: basic concepts and definitions. Clinical Chemistry 40, 17971799.CrossRefGoogle ScholarPubMed
Kamen, M (1963) The early history of carbon-14. Journal of Chemical Education 40, 234242.CrossRefGoogle Scholar
Katz, J & Lee, WNP (1991) Application of mass isotomer analysis for determination of pathways of glycogen synthesis. American Journal of Physiology 261, E332E336.Google ScholarPubMed
Kohler, RE Jr (1977) Rudolf Schoenheimer, isotopic tracers and biochemistry in the 1930's. In Historical Studies in the Physical Sciences, vol. 8, pp. 257298 [McCormmach, R and Pyenson, L, editors]. Baltimore, MD: Johns Hopkins University Press.Google Scholar
Koshland, DE Jr (1992) The molecule of the year. Science 258, 1861.CrossRefGoogle ScholarPubMed
Koshland, DE Jr (1998) The era of pathway quantification. Science 280, 852853.CrossRefGoogle ScholarPubMed
Kreider, RB, Ferreira, M, Wilson, M, Grindstaff, P, Plisk, S, Reinardy, J, Cantler, E & Almada, AL (1998) Effects of creatine supplementation on body composition, strength and sprint performance. Medicine and Science in Sports and Exercise 30, 7382.CrossRefGoogle ScholarPubMed
Kubota, K, Matsuzawa, T, Ito, M, Ito, K, Fujiwara, T, Abe, Y, Toshioka, S, Fukuda, H, Hatazawa, J, Iwata, R, Watanuki, S & Ido, T (1985) Lung tumor imaging by positron emission tomography using C-11-l-methionine. Journal of Nuclear Medicine 26, 3742.Google Scholar
LaFrance, ND, O'Tauma, L, Villemagne, V, Williams, J, Douglas, K, Dannals, RF, Ravert, H, Wilson, A, Drew, H, Links, J, Wong, D, Carson, B, Brem, H, Strauss, L & Wagner, HN (1987) Quantitative imaging and follow-up experience of C-11-l-methionine accumulation in brain tumors with positron emission tomography. Journal of Nuclear Medicine 26, 3742.Google Scholar
Lagerwerf, FM, Wever, RMF, van Rijn, HJM, Versluis, C, Herrma, W, Haverkamp, J, Koomans, HA, Robelink, TJ & Boer, P (1998) Assessment of nitric oxide production by measurement of [15N]citrulline enrichment in human plasma using high performance liquid chromatography-mass spectrometry. Analytical Biochemistry 257, 4552.CrossRefGoogle ScholarPubMed
Landau, BR, Chandramouli, V, Schumann, WC, Ekberg, K, Kumaran, K, Kalhan, SC & Wahren, J (1995) Estimates of Krebs cycle activity and contributions of gluconeogenesis to hepatic glucose production in fasting healthy subjects and IDDM patients. Diabetologia 38, 831838.CrossRefGoogle ScholarPubMed
Larsen, CS, Schoeninger, MJ, van der Merwe, NJ, Moore, KM & Lee-Throp, JA (1992) Carbon and nitrogen isotopic signatures of human dietary change in the Georgia Bight. American Journal of Physical Anthropology 89, 197214.CrossRefGoogle ScholarPubMed
Lifson, N, Gordon, GB & McClintock, R (1955) Measurement of total carbon dioxide by means of D218O. Journal of Applied Physiology 7, 704710.CrossRefGoogle Scholar
Links, JM (1994) Instrumentation. In Nuclear Medicine. Technology and Techniques, 3rd ed., pp.5385 [Bernier, DR, Christian, PR and Langan, JK, editors]. St Louis, MO: Mosby.Google Scholar
Macallan, DC, Fullerton, CA, Neese, RA, Haddock, K, Park, SS & Hellerstein, MK (1998) Measurement of cell proliferation by labelling of DNA with stable isotope-labeled glucose: Studies in vitro, in animals, and in humans. Proceedings of the National Academy of Sciences USA 95, 708713.CrossRefGoogle ScholarPubMed
Macallan, DC, Smith, LM, Ferber, J, Milne, E, Griffin, GE, Benjamin, N & McNurlan, M (1997) Measurement of NO synthesis in humans by l-[15N2]arginine: application to the response to vaccination. American Journal of Physiology 272, R1888R1896.Google Scholar
McEuen, PL (1998) Carbon-based electronics. Nature 393, 1517.CrossRefGoogle Scholar
McNurlan, MA, Essen, P, Heys, SD, Buchan, V, Garlick, PJ & Wernerman, J (1991) Measurement of protein synthesis in human skeletal muscle: further investigation of the flooding technique. Clinical Science 81, 557564.CrossRefGoogle ScholarPubMed
Marchini, JS, Castillo, L, Chapman, TE, Vogt, J, Ajami, A & Young, VR (1993) Phenylalanine conversion to tyrosine: Comparative determination with l-[ring-2H5]phenylalanine and l[l-13C]phenylalanine as tracers in man. Metabolism 42, 13161322.CrossRefGoogle Scholar
Matthews, DE & Bier, DM (1983) Stable isotope methods for nutritional investigation. Annual Reviews of Nutrition 3, 309339.CrossRefGoogle ScholarPubMed
Matthews, DE, Bier, DM, Rennie, MJ, Edwards, RHT & Halliday, D (1981) Regulation of leucine metabolism in man: a stable isotope study. Science 214, 11291131.CrossRefGoogle Scholar
Mazoyer, BM, Heiss, WD & Comar, D (1993) PET Studies on Amino Acid Metabolism and Protein Synthesis. Dordrecht, The Netherlands: Kluwer Academic Publishers.CrossRefGoogle Scholar
Mbikay, M, Todros, H, Isheda, N, Lerner, CP, Lamirande, E, de Chen, A, El-Alfy, M, Clermont, Y, Seidah, NG, Chrétien, M, Gagnon, C & Simpson, EM (1997) Impaired fertility in mice deficient for the testicular germ-cell protease PC4. Proceedings of the National Academy of Sciences USA 94, 68426846.CrossRefGoogle ScholarPubMed
Miller, RJ, Jahoor, F & Jaksic, T (1995 a) Decreased cysteine and proline synthesis in parenterally-fed, premature infants. Journal of Pediatric Surgery 30, 953957.CrossRefGoogle ScholarPubMed
Miller, RJ, Jahoor, F, Reeds, PJ, Heird, WC & Jaksic, T (1995 b) A new stable isotope technique to assess human neonatal amino acid synthesis. Journal of Pediatric Surgery 30, 13251329.CrossRefGoogle ScholarPubMed
Millward, DJ, Price, G, Pacy, PJH & Halliday, D (1991) Whole body protein and amino acid turnover in man: what can we measure with confidence? Proceedings of the Nutrition Society 50, 197216.CrossRefGoogle ScholarPubMed
Molnar, JA, Alpert, NM, Burke, JF & Young, VR (1986) Synthesis and degradation rates of collagen in vivo in whole skin of rats, studied with 18O2 labelling. Biochemical Journal 240, 431435.CrossRefGoogle ScholarPubMed
Mosskin, M, von Hjolst, H, Bergstrom, M, Collins, VP, Ericksson, L, Johnstrom, P & Norén, G (1987) Positron emission tomography with 11C-methionine and computed tomography of intracranial tumors compared with histopathologies examination of multiple biopsies. Acta Radiologa 28, 673681.Google ScholarPubMed
Nair, KS, Welle, SL, Halliday, D & Campbell, RG (1988) Effect of β-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans. Journal of Clinical Investigation 82, 198205.CrossRefGoogle ScholarPubMed
Nuutila, P, Knuuti, J, Ruotsalainen, U, Koivisto, VA, Eronen, E, Teräs, M, Bergman, J, Haaparanta, M, Voipio-Pulkka, L-M, Viikari, J, Rönnemaa, T, Wegelius, U & Yki-Järvomem, J (1993) Insulin resistance is localized to skeletal but not heart muscle in type I diabetes. American Journal of Physiology 264, E756E763.Google ScholarPubMed
Neese, RA, Schwartz, JM, Faix, D, Turnver, S, Letscher, A, Vu, D & Hellerstein, MK (1995) Gluconeogenesis and intrahepatic triose phosphate flux in response to fasting or substrate loads. Application of the mass isotomer distribution analysis technique with testing of assumptions and potential problems. Journal of Biological Chemistry 27, 1445214463.CrossRefGoogle Scholar
Novotny, JA, Dueker, SR, Zech, LA & Clifford, AJ (1995) Compartmental analysis of the dynamics of β-carotene metabolism in an adult volunteer. Journal of Lipid Research 36, 18251838.CrossRefGoogle Scholar
Olson, RE (1997) The dynamic state of body constituents (Schoenheimer, 1939). Journal of Nutrition 127, 1041S1043S.Google ScholarPubMed
Paans, AM, Prium, J, van Waarde, A, Willemsen, AT & Vaalburg, W (1996) Radiolabeled tyrosine for the measurement of protein synthesis rate in vivo by positron emission tomography. Ballière's Clinical Endocrinology and Metabolism 10, 497510.CrossRefGoogle ScholarPubMed
Palombella, VJ, Rando, OJ, Goldberg, AL & Maniatis, T (1994) The ubiquitin-proteasome pathway is required for processing the NK-kappa B1 precursor protein and the activation of NF-kappa B. Cell 78, 773785.CrossRefGoogle Scholar
Pannemans, DL, Wagenmakers, AJ, Westerterp, KR, Schaafima, G & Halliday, D (1997) The effect of an increase of protein intake on whole-body protein turnover in elderly women is tracer dependent. Journal of Nutrition 127, 17881794.CrossRefGoogle ScholarPubMed
Patterson, BW (1997) Use of stable isotopically labeled tracers for studies of metabolic kinetics: An overview. Metabolism 46, 322329.CrossRefGoogle ScholarPubMed
Patterson, BW, Zhang, XJ, Chen, Y, Klein, S & Wolfe, RR (1997) Measurement of very low stable isotope enrichments by gas chromatography/mass spectrometry: application to measurement of muscle protein synthesis. Metabolism 46, 943948.CrossRefGoogle ScholarPubMed
Phelps, ME, Massiotta, JC & Schelbert, HR (editors) (1986) In Positron Emission Tomography and Autoradiography. Principles and Applications for the Brain and Heart.New York: Raven Press.Google Scholar
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. Clinical Science 36, 283296.Google ScholarPubMed
Picou, D, Taylor-Roberts, T & Waterlow, JC (1969) The measurement of total protein synthesis and nitrogen flux in man by constant infusion of 15N-glycine. Proceedings of the Physiological Society 200, 52P53P.Google Scholar
Planas, AM, Prenant, C, Mazoyer, BM, Comar, D & DiGiamberardino, L (1992) Regional cerebral l-[14C-Methyl]methionine incorporation into proteins: Evidence for methionine recycling in the rat brain. Journal of Cerebral Blood Flow and Metabolism 12, 603612.CrossRefGoogle ScholarPubMed
Raichle, ME, Martin, WRW, Herscovitch, P, Mintum, MA & Markham, J (1983) Brain blood flow measured with intravenous H215O. II. Implementation and validation. Journal of Nuclear Medicine 24, 790798.Google ScholarPubMed
Ratner, S (1979) The dynamic state of body proteins. Annals of the New York Academy of Sciences 325, 189209.CrossRefGoogle ScholarPubMed
Rennie, MJ, Edwards, RH, Halliday, D, Matthews, DE, Wolman, SL & Millward, DJ (1982) Muscle protein synthesis measured by stable isotope techniques in man: the effects of feeding and fasting. Clinical Science 63, 519523.CrossRefGoogle ScholarPubMed
Rittenberg, D, Keston, AS, Rosebury, F & Schoenheimer, R (1939) Studies in protein metabolism. II. The determination of nitrogen isotopes in organic compounds. Journal of Biological Chemistry 127, 291299.CrossRefGoogle Scholar
Rittenberg, D & Schoenheimer, R (1935) Deuterium as an indicator in the study of intermediary metabolism. II. Methods. Journal of Biological Chemistry 111, 169174.CrossRefGoogle Scholar
Rittenberg, D & Schoenheimer, R (1939) Studies in protein metabolism. VI. Hippuric acid formation studied with the aid of the nitrogen isotope. Journal of Biological Chemistry 127, 329331.CrossRefGoogle Scholar
Robertson, JS (editor) (1983) Historical Development. In The Compartmental Distribution of Radiotracers, pp. 19. Boca Raton, FL: CRC Press.Google Scholar
Rolfe, DFS & Brown, GC (1997) Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiological Reviews 77, 731758.CrossRefGoogle ScholarPubMed
Roth, E (1997) Critical evaluation of the rise and analysis of stable isotopes (Technical Report). Pure and Applied Chemistry 69, 17531828.CrossRefGoogle Scholar
Rousell, R, Cartier, PG, Robert, J-J, Velho, G & Block, G (1998) 13C/31P NMR studies of glucose transport in human skeletal muscle. Proceedings of the National Academy of Sciences USA 95, 13131318.CrossRefGoogle Scholar
Saccomani, MP, Bonadonna, RC, Caveggion, E, DeFranzo, RA & Cobelli, C (1995) Bicarbonate kinetics in humans: identification and validation of a three compartment model. American Journal of Physiology 269, E183E192.Google ScholarPubMed
Schelbert, RR & Schwaiger, M (1986) PET studies of the heart. In Positron Emission Tomography and Autoradiography. Principles and Applications for the Brain and Heart, pp. 581661 [Phelps, ME, Mazziotta, TC and Schelbert, HR, editors]. New York: Raven Press.Google Scholar
Schoeller, DA & van Santen, E (1982) Measurement of energy expenditure in humans by doubly-labeled water method. Journal of Applied Physiology 53, 955959.CrossRefGoogle ScholarPubMed
Schoenheimer, R (1931) New contributions in sterol metabolism. Science 74, 579584.CrossRefGoogle ScholarPubMed
Schoenheimer, R (19361937) The investigation of intermediary metabolism with the aid of heavy hydrogen. The Harvey Lectures, series 32, pp.122144. Baltimore, MD: Williams & Wilkins Co.Google Scholar
Schoenheimer, R (1942) The Dynamic State of Body Constituents. Cambridge, MA: Harvard University Press.Google Scholar
Schoenheimer, R & Ratner, S (1939) Studies in protein metabolism. III. Synthesis of amino acids containing isotopic nitrogen. Journal of Biological Chemistry 127, 301313.CrossRefGoogle Scholar
Schoenheimer, R, Ratner, S & Rittenberg, D (1939 a) Studies in protein metabolism. X. The metabolic activity of body proteins investigated with (-)-leucine containing two isotopes. Journal of Biological Chemistry 130, 703732.CrossRefGoogle Scholar
Schoenheimer, R, Ratner, S & Rittenberg, D (1939 b) Studies in protein metabolism. VII. The metabolism of tyrosine. Journal of Biological Chemistry 127, 334344.CrossRefGoogle Scholar
Schoenheimer, R & Rittenberg, D (1935) Deuterium as an indicator in the study of intermediary metabolism. III. The role of the fat tissues. Journal of Biological Chemistry 111, 175181.CrossRefGoogle Scholar
Schoenheimer, R & Rittenberg, D (1938) The application of isotopes to the study of intermediary metabolism. Science 87, 221226.CrossRefGoogle Scholar
Seidell, JC (1998) Dietary fat and obesity: an epidemiologic perspective. American Journal of Clinical Nutrition 67, Suppl., 546S550S.CrossRefGoogle ScholarPubMed
Shulman, GI (1997) Nuclear magnetic resonance studies of liver and muscle glycogen metabolism in humans. In Emerging Technologies for Nutrition Research, pp. 259272 [Carlson-Newberry, S and Costello, RB, editors]. Washington, DC: National Academy Press.Google Scholar
Sibson, NR, Dhankar, A, Masson, GF, Behar, KL, Rothman, DL & Shulman, RG (1997) In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate-glutamine cycling. Proceedings of the National Academy of Sciences USA 94, 26992704.CrossRefGoogle ScholarPubMed
Stalnacke, C-G, Jones, B, Langstron, B, Lundquist, H, Malmborg, P, Sjorberg, S & Larsson, B (1982) Short-lived radionuclides in nutritional physiology. A model study with l-[Me-11C]methionine in the pig. British Journal of Nutrition 47, 537545.CrossRefGoogle Scholar
Stanley, CA, Lieu, YK, Hsu, BYL, Burlina, BB, Greenberg, CR, Hopwood, NJ, Perlman, K, Rich, BH, Zammarchi, E & Poncz, M (1998) Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene. New England Journal of Medicine 338, 13521357.CrossRefGoogle ScholarPubMed
Storch, KJ, Wagner, DA, Burke, JF & Young, VR (1988) Quantitative study in vivo of methionine cycle in humans using [methyl-2H2] and [1-13C]methionine. American Journal of Physiology 255, E322E331.Google ScholarPubMed
Stroud, MA, Jackson, AA & Waterlow, JC (1996) Protein turnover rates of two human subjects during an unassisted crossing of Antarctica. British Journal of Nutrition 76, 165174.CrossRefGoogle ScholarPubMed
Ter-Pogossian, MM, Raichle, ME & Sobel, BE (1980) Positron-emission tomography. Scientific American 243, 171181.CrossRefGoogle ScholarPubMed
Tessari, P, Inchiostro, S, Zanetti, M & Barazzoni, R (1995) A model of skeletal muscle leucine kinetics measured across the forearm. American Journal of Physiology 269, E127E136.Google Scholar
Treacy, E, Pitt, JJ, Seller, K, Thompson, GN, Ramus, J & Cotton, RG (1996) In vivo disposal of phenylalanine in phenylketonuria: a study of two siblings. Journal of Inherited Metabolic Disease 19, 595602.CrossRefGoogle ScholarPubMed
Urey, HC, Brickwedde, FG & Murphy, GM (1932) A hydrogen isotope of mass 2. Physical Reviews 40, 115.CrossRefGoogle Scholar
Volek, JS, Kraemer, WJ, Bush, JA, Boetes, M, Incledan, T, Clark, KL & Lynch, JM (1997) Creatine supplementation enhances muscular performance during high-intensity resistance exercise. Journal of the American Dietetic Association 97, 765770.CrossRefGoogle ScholarPubMed
Volpi, E, Ferrando, AA, Yeckel, CW, Tipton, KD & Wolfe, RR (1998) Exogenous amino acids stimulate net muscle protein synthesis in the elderly. Journal of Clinical Investigation 101, 20002007.CrossRefGoogle ScholarPubMed
Wastney, ME, Subramanian, S, Broering, N & Boston, R (1997) Using models to explore whole-body metabolism and accessing models through a model library. Metabolism 46, 330332.CrossRefGoogle ScholarPubMed
Waterlow, JC (1995) Whole-body protein turnover in humans - past, present, and future. Annual Reviews of Nutrition 15, 5792.CrossRefGoogle ScholarPubMed
Waterlow, JC, Garlick, PJ & Millward, DJ (1978) Protein Turnover in Mammalian Tissues and in the Whole Body. Amsterdam: North Holland Publishing Company.Google Scholar
Welle, S, Thornton, C, Statt, M & McHenry, B (1994) Postprandial myofibrillar and whole body protein synthesis in young and old subjects. American Journal of Physiology 267, E599E604.Google Scholar
White, CD & Armelagos, GJ (1997) Osteopenia and stable isotope ratios in bone collagen of Nubian female mummies. American Journal of Physical Anthropology 103, 185189.3.0.CO;2-#>CrossRefGoogle ScholarPubMed
Wiechert, W & de Graaf, AA (1996) In vivo stationary flux analysis by 13C labelling experiments. Advances in Biochemical Engineering 54, 109154.Google Scholar
Willett, WC (1998) Is dietary fat a major determinant of body fat? American Journal of Clinical Nutrition 67, Suppl., 556S562S.CrossRefGoogle Scholar
Wilson, EK (1998) Instant DNA detection. Chemical Engineering and News 76, 4749.CrossRefGoogle Scholar
Wolfe, RR (1992) Radioactive and Stable Isotope Tracers in Biomedicine: Principles and Practice of Kinetic Analysis. New York: Wiley–Liss.Google Scholar
Wong, WW (1996) Total energy expenditure of free-living humans can be estimated with the doubly labeled water method. Advances in Food and Nutrition Research 40, 171180.CrossRefGoogle ScholarPubMed
Woolley, AT, Lao, K, Glazer, AN & Mothies, RA (1998) Capillary electrophoresis chips with integrated electrochemical detection. Analytical Chemistry 70, 684688. mailto: CrossRefGoogle ScholarPubMed
Yang, L-Y, Kuksis, A, Myher, JJ & Steiner, G (1996) Contributions of de novo fatty acid synthesis to very low density lipoprotein triacylglycerols: evidence from mass isotopomer distribution analysis of fatty acids synthesized from [2H6]ethanol. Journal of Lipid Research 37, 262274.CrossRefGoogle ScholarPubMed
Yarasheski, KE, Campbell, JA, Smith, K, Rennie, MJ, Holloszy, JO & Bier, DM (1992) Effect of growth hormone and resistance exercise on muscle growth in young men. American Journal of Physiology 262, E261E267.Google ScholarPubMed
Young, VR, Yu, YM, Hsu, H, Babich, JW, Alpert, N, Tompkins, RG & Fischman, AJ (1997) Combined stable isotope-positron emission tomography for in vivo assessment of protein metabolism. In Emerging Technologies for Nutrition Research, pp. 231257 [Carlson-Newberry, S and Costello, RB, editors]. Washington, DC: National Academy Press.Google Scholar
Yu, Y-M, Burke, JF, Vogt, JA, Chambers, L & Young, VR (1992) Splanchnic and whole body l-[1-13C, 15N]leucine kinetics in relation to enteral and parenteral amino acid supply. American Journal of Physiology 262, E687E694.Google Scholar
Yu, Y-M, Tompkins, RG, Ryan, CM & Young, VR (1998) The metabolic basis for the rise in energy expenditure in severely burned patients. Journal of Parenteral and Enteral Nutrition (In the Press).Google Scholar