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Isotope Enhanced Approaches in Metabolomics

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Isotope labeling in Biomolecular NMR

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 992))

Abstract

The rapidly growing area of “metabolomics,” in which a large number of metabolites from body fluids, cells or tissue are detected quantitatively, in a single step, promises immense potential for a number of disciplines including early disease diagnosis, therapy monitoring, systems biology, drug discovery and nutritional science. Because of its ability to detect a large number of metabolites in intact biological samples reproducibly and quantitatively, nuclear magnetic resonance (NMR) spectroscopy has emerged as one of the most powerful analytical techniques in metabolomics. NMR spectroscopy of biological samples with isotope labeling of metabolites using nuclei such as 2H, 13C, 15N and 31P, either in vivo or ex vivo, has dramatically improved our ability to identify low concentrated metabolites and trace important metabolic pathways. Considering the somewhat limited sensitivity and high complexity of NMR spectra of biological samples, efforts have been made to increase sensitivity and selectivity through isotope labeling methods, which pave novel avenues to unravel biological complexity and understand cellular functions in health and various disease conditions. This chapter describes current developments in isotope labeling of metabolites in vivo as well as ex vivo, and their potential metabolomics applications.

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References

  1. Nicholson JK, Lindon JC, Holmes E (1999) ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 29:1181–1189

    PubMed  CAS  Google Scholar 

  2. Fiehn O (2002) Metabolomics-the link between genotype and phenotype. Plant Mol Biol 48:155–171

    PubMed  CAS  Google Scholar 

  3. Saghatelian A, Cravatt BF (2005) Global strategies to integrate the proteome and metabolome. Curr Opin Chem Biol 9:62–68

    PubMed  CAS  Google Scholar 

  4. Assfalg M, Bertini I, Colangiuli D et al (2008) Evidence of different metabolic phenotypes in humans. Proc Natl Acad Sci USA 105:1420–1424

    PubMed  CAS  Google Scholar 

  5. Nicholson JK, Lindon JC (2008) Systems biology: metabonomics. Nature 455:1054–1056

    PubMed  CAS  Google Scholar 

  6. van der Greef J, Smilde AK (2005) Symbiosis of chemometrics and metabolomics: past, present, and future. J Chemom 19:376–386

    Google Scholar 

  7. Nagana Gowda GA, Zhang S, Gu H et al (2008) Metabolomics based methods for early disease diagnostics: a review. Exp Rev Mol Diagn 8:627–633

    Google Scholar 

  8. NaganaGowda GA, Ijare OB, Shanaiah N et al (2009) Combining NMR spectroscopy and mass spectrometry in biomarker discovery. Biomark Med 3:307–322

    Google Scholar 

  9. Holmes E, Wilson ID, Nicholson JK (2008) Metabolic phenotyping in health and disease. Cell 134:714–717

    PubMed  CAS  Google Scholar 

  10. Weljie AM, Newton J, Mercier P et al (2006) Targeted profiling: quantitative analysis of 1H NMR metabolomics data. Anal Chem 78:4430–4442

    PubMed  CAS  Google Scholar 

  11. Lewis IA, Schommer SC, Hodis B et al (2007) Method for determining molar concentrations of metabolites in complex solutions from two-dimensional 1H-13C NMR spectra. Anal Chem 79:9385–9390

    PubMed  CAS  Google Scholar 

  12. Robinette SL, Zhang F, Brüschweiler-Li L et al (2008) Web server based complex mixture analysis by NMR. Anal Chem 80:3606–3611

    PubMed  CAS  Google Scholar 

  13. Chikayama E, Sekiyama Y, Okamoto M et al (2010) Statistical indices for simultaneous large-scale metabolite detections for a single NMR spectrum. Anal Chem 82:1653–1658

    PubMed  CAS  Google Scholar 

  14. Keun HC (2006) Metabonomic modeling of drug toxicity. Pharmacol Ther 109:92–106

    PubMed  CAS  Google Scholar 

  15. Coen M, Holmes E, Lindon JC et al (2008) NMR-based metabolic profiling and metabonomic approaches to problems in molecular toxicology. Chem Res Toxicol 2:9–27

    Google Scholar 

  16. Bollard ME, Stanley EG, Lindon JC et al (2005) NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition. NMR Biomed 18:143–162

    PubMed  CAS  Google Scholar 

  17. Nagana Gowda GA, Ijare OB, Somashekar BS et al (2006) Single-step analysis of individual conjugated bile acids in human bile using 1H NMR spectroscopy. Lipids 41:591–603

    Google Scholar 

  18. Nagana Gowda GA (2010) Human bile as a rich source of biomarkers for hepatopancreatobiliary cancers. Biomark Med 4:299–314

    Google Scholar 

  19. Nagana Gowda GA (2011) NMR spectroscopy for discovery and quantitation of biomarkers of disease in human bile. Bioanalysis 3:1877–1890

    Google Scholar 

  20. Bala L, Ghoshal UC, Ghoshal U et al (2006) Malabsorption syndrome with and without small intestinal bacterial overgrowth: a study on upper-gut aspirate using 1H NMR spectroscopy. Magn Reson Med 56:738–744

    PubMed  Google Scholar 

  21. Griffin JL, Kauppinen RA (2007) Tumour metabolomics in animal models of human cancer. J Proteome Res 6:498–505

    PubMed  CAS  Google Scholar 

  22. Villas-Boas SG, Hojer-Pedersen J, Akesson M et al (2005) Global metabolite analysis of yeast: evaluation of sample preparation methods. Yeast 22:1155–1169

    PubMed  CAS  Google Scholar 

  23. Bollard ME, Xu JS, Purcell W et al (2002) Metabolic profiling of the effects of D-galactosamine in liver spheroids using 1H NMR and MAS-NMR spectroscopy. Chem Res Toxicol 15:1351–1359

    PubMed  CAS  Google Scholar 

  24. Boroujerdi AF, Vizcaino MI, Meyers A et al (2009) NMR-based microbial metabolomics and the temperature-dependent coral pathogen Vibrio coralliilyticus. Environ Sci Technol 43:7658–7664

    PubMed  CAS  Google Scholar 

  25. Lyng H, Sitter B, Bathen TF et al (2007) Metabolic mapping by use of high-resolution magic angle spinning 1H MR spectroscopy for assessment of apoptosis in cervical carcinomas. BMC Cancer 7:11

    PubMed  Google Scholar 

  26. Sitter B, Bathen T, Hagen B et al (2004) Cervical cancer tissue characterized by high-resolution magic angle spinning MR spectroscopy. Magn Reson Mater Phys Biol Med 16:174–181

    CAS  Google Scholar 

  27. Schenetti L, Mucci A, Parenti F et al (2006) HR-MAS NMR spectroscopy in the characterization of human tissues: application to healthy gastric mucosa. Concepts Magn Reson A 28A:430–443

    CAS  Google Scholar 

  28. Beckonert O, Keun HC, Ebbels TMD et al (2007) Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat Protoc 2:2692–2703

    PubMed  CAS  Google Scholar 

  29. Beckonert O, Coen M, Keun HC et al (2010) High-resolution magic-angle-spinning NMR spectroscopy for metabolic profiling of intact tissues. Nat Protoc 5:1019–1032

    PubMed  CAS  Google Scholar 

  30. Nicholson JK, Foxall PJD, Spraul M et al (1995) 750 MHz 1H and 1H-13C NMR spectroscopy of human blood-plasma. Anal Chem 67:793–811

    PubMed  CAS  Google Scholar 

  31. Balayssac S, DelsucM-A GV et al (2009) Two-dimensional DOSY experiment with Excitation Sculpting water suppression for the analysis of natural and biological media. J Magn Reson 196:78–83

    PubMed  CAS  Google Scholar 

  32. Van Lokeren L, Kerssebaum R, Willem R et al (2008) ERETIC implemented in diffusion-ordered NMR as a diffusion reference. Magn Reson Chem 46:S63–S71

    PubMed  Google Scholar 

  33. Smith LM, Maher AD, Cloarec O et al (2007) Statistical correlation and projection methods for improved information recovery from diffusion-edited NMR spectra of biological samples. Anal Chem 79:5682–5689

    PubMed  CAS  Google Scholar 

  34. Simpson AJ, Brown SA (2005) Purge NMR: effective and easy solvent suppression. J Magn Reson 175:340–346

    PubMed  CAS  Google Scholar 

  35. Ogg RJ, Kingsley PB, Taylor JS (1994) Wet, a T-1-insensitive and B-1-insensitive water-suppression method for in-vivo localized 1H NMR spectroscopy. J Magn Reson B 104:1–10

    PubMed  CAS  Google Scholar 

  36. Mo H, Raftery D (2008) Improved residual water suppression: WET180. J Biomol NMR 41:105–111

    PubMed  CAS  Google Scholar 

  37. Hoult DI (1976) Solvent peak saturation with single-phase and quadrature fourier transformation. J Magn Reson 21:337–347

    CAS  Google Scholar 

  38. Sandusky P, Raftery D (2005) Use of selective TOCSY NMR experiments for quantifying minor components in complex mixtures: application to the metabonomics of amino acids in honey. Anal Chem 77:2455–2463

    PubMed  CAS  Google Scholar 

  39. Sandusky P, Raftery D (2005) Use of semiselective TOCSY and the pearson correlation for the metabonomic analysis of biofluid mixtures: application to urine. Anal Chem 77:7717–7723

    PubMed  CAS  Google Scholar 

  40. Sandusky P, Appiah-Amponsah E, Raftery D (2011) Use of optimized 1D TOCSY NMR for improved quantitation and metabolomic analysis of biofluids. J Biomol NMR 49:281–290

    PubMed  CAS  Google Scholar 

  41. Dumas ME, Canlet C, André F et al (2002) Metabonomic assessment of physiological disruptions using 1H-13C HMBC-NMR spectroscopy combined with pattern recognition procedures performed on filtered variables. Anal Chem 74:2261–2273

    PubMed  CAS  Google Scholar 

  42. Tang HR, Wang Y, Nicholson JK et al (2004) Use of relaxation-edited one-dimensional and two dimensional nuclear magnetic resonance spectroscopy to improve detection of small metabolites in blood plasma. Anal Biochem 325:260–272

    PubMed  CAS  Google Scholar 

  43. Xi Y, de Ropp JS, Viant MR et al (2006) Automated screening for metabolites in complex mixtures using 2D COSY NMR spectroscopy. Metabolomics 2:221–233

    CAS  Google Scholar 

  44. Chikayama E, Suto M, Nishihara T et al (2008) Systematic NMR analysis of stable isotope labeled metabolite mixtures in plant and animal systems: coarse grained views of metabolic pathways. PLoS One 3:e3805

    PubMed  Google Scholar 

  45. Fan TWM, Bandura LL, Higashi RM et al (2005) Metabolomics-edited transcriptomics analysis of Se anticancer action in human lung cancer cells. Metabolomics 1:325–339

    CAS  Google Scholar 

  46. Ludwig C, Viant MR (2010) Two-dimensional J-resolved NMR spectroscopy: review of a key methodology in the metabolomics toolbox. Phytochem Anal 21:22–32

    PubMed  CAS  Google Scholar 

  47. Parsons HM, Ludwig C, Gunther UL et al (2007) Improved classification accuracy in 1-and 2-dimensional NMR metabolomics data using the variance stabilising generalised logarithm transformation. BMC Bioinform 8:234

    Google Scholar 

  48. Hyberts SG, Heffron GJ, Tarragona NG et al (2007) Ultrahigh-resolution 1H-13C HSQC spectra of metabolite mixtures using nonlinear sampling and forward maximum entropy reconstruction. J Am Chem Soc 129:5108–5116

    PubMed  CAS  Google Scholar 

  49. Viant MR (2003) Improved methods for the acquisition and interpretation of NMR metabolomic data. Biochem Biophys Res Commun 310:943–948

    PubMed  CAS  Google Scholar 

  50. Lindon JC, Holmes E, Nicholson JK (2006) Metabonomics techniques and applications to pharmaceutical research & development. Pharm Res 23:1075–1088

    PubMed  CAS  Google Scholar 

  51. Kind T, Tolstikov V, Fiehn O et al (2007) A comprehensive urinary metabolomic approach for identifying kidney cancer. Anal Biochem 363:185–195

    PubMed  CAS  Google Scholar 

  52. Wilson ID, Nicholson JK, Castro-Perez J et al (2005) High resolution “ultra performance” liquid chromatography coupled to a-TOF mass spectrometry as a tool for differential metabolic pathway profiling in functional genomic studies. J Proteome Res 4:591–598

    PubMed  CAS  Google Scholar 

  53. Spraul M, Freund AS, Nast RE et al (2003) Advancing NMR sensitivity for LC-NMR-MS using a cryo-flow probe: application to the analysis of acetaminophen metabolites in urine. Anal Chem 75:1536–1541

    PubMed  CAS  Google Scholar 

  54. Lacey ME, Subramanian R, Olson DL et al (1999) High-resolution NMR spectroscopy of sample volumes from 1 nL to 10 μL. Chem Rev 99:3133–3152

    PubMed  CAS  Google Scholar 

  55. Olson DL, Peck TL, Webb AG et al (1995) High-resolution microcoil 1H-NMR for mass-limited, nanoliter-volume samples. Science 270:1967–1970

    CAS  Google Scholar 

  56. Webb AG (2005) Microcoil nuclear magnetic resonance spectroscopy. J Pharm Biomed Anal 38:892–903

    PubMed  CAS  Google Scholar 

  57. Kc R, Henry ID, Park GHJ et al (2009) Design and construction of a versatile dual volume heteronuclear double resonance microcoil NMR probe. J Magn Reson 197:186–192

    PubMed  Google Scholar 

  58. Henry D, Park GHJ, Kc R et al (2008) Design and construction of a microcoil NMR probe for the routine analysis of 20-mu L samples. Concepts Magn Reson B Magn Reson Eng 33B:1–8

    Google Scholar 

  59. Bergeron SJ, Henry ID, Santini RE et al (2008) Saturation transfer double-difference NMR spectroscopy using a dual solenoid microcoil difference probe. Magn Reson Chem 46:925–929

    PubMed  CAS  Google Scholar 

  60. Kc R, Gowda YN, Djukovic D et al (2010) Susceptibility-matched plugs for microcoil NMR probes. J Magn Reson 205:63–68

    PubMed  Google Scholar 

  61. Guo K, Bamforth F, Li L (2011) Qualitative metabolome analysis of human cerebrospinal fluid by 13C-/12C-isotope dansylation labeling combined with liquid chromatography fourier transform ion cyclotron resonance mass spectrometry. J Am Soc Mass Spectrom 22:339–347

    PubMed  CAS  Google Scholar 

  62. Huang X, Regnier FE (2008) Differential metabolomics using stable isotope labeling and two-dimensional gas chromatography with time-of-flight mass spectrometry. Anal Chem 80:107–114

    PubMed  CAS  Google Scholar 

  63. Yang WC, Adamec J, Regnier FE (2007) Enhancement of the LC/MS analysis of fatty acids through derivatization and stable isotope coding. Anal Chem 79:5150–5157

    PubMed  CAS  Google Scholar 

  64. Yang WC, Regnier FE, Sliva D et al (2008) Stable isotope-coded quaternization for comparative quantification of estrogen metabolites by high-performance liquid chromatography-electrospray ionization mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 870:233–240

    CAS  Google Scholar 

  65. Lane AN, Fan TWM, Bousamra M II et al (2011) Stable isotope-resolved metabolomics (SIRM) in cancer research with clinical application to nonsmall cell lung cancer. OMICS A J Integr Biol 15:173–182

    CAS  Google Scholar 

  66. Fan TW, Lane AN, Higashi RM et al (2011) Stable isotope resolved metabolomics of lung cancer in a SCID mouse model. Metabolomics 7:257–269

    PubMed  CAS  Google Scholar 

  67. Fan TW, Lane AN, Higashi RM et al (2009) Altered regulation of metabolic pathways in human lung cancer discerned by (13)C stable isotope-resolved metabolomics (SIRM). Mol Cancer 8:41

    PubMed  Google Scholar 

  68. Locasale JW, Grassian AR, Melman T et al (2011) Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat Genet 43:869–874

    PubMed  CAS  Google Scholar 

  69. Fan TW, Lane AN (2011) NMR-based stable isotope resolved metabolomics in systems biochemistry. J Biomol NMR 49:267–280

    PubMed  CAS  Google Scholar 

  70. Petch D, Butler M (1994) Profile of energy metabolism in a murine hybridoma: glucose and glutamine utilization. J Cell Physiol 161:71–76

    PubMed  CAS  Google Scholar 

  71. Portais JC, Voisin P, Merle M et al (1996) Glucose and glutamine metabolism in C6 glioma cells studied by carbon-13 NMR. Biochimie 78:155–164

    PubMed  CAS  Google Scholar 

  72. Mazurek S, Grimm H, Oehmke M et al (2000) Tumor M2-PK and glutaminolytic enzymes in the metabolic shift of tumor cells. Anticancer Res 20(6D):5151–5154

    PubMed  CAS  Google Scholar 

  73. DeBerardinis RJ, Mancuso A, Daikhin E et al (2007) Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA 104:19345–19350

    PubMed  CAS  Google Scholar 

  74. Lane AN, Fan TW, Higashi RM et al (2009) Prospects for clinical cancer metabolomics using stable isotope tracers. Exp Mol Pathol 86:165–173

    PubMed  CAS  Google Scholar 

  75. Lloyd SG, Zeng H, Wang P et al (2004) Lactate isotopomer analysis by 1H NMR spectroscopy: consideration of long-range nuclear spin-spin interactions. Magn Reson Med 51:1279–1282

    PubMed  CAS  Google Scholar 

  76. Lane AN, Fan TW (2007) Quantification and identification of isotopomer distributions of metabolites in crude cell extracts using 1H TOCSY. Metabolomics 3:79–86

    CAS  Google Scholar 

  77. Burgess SC, Babcock EE, Jeffrey FM et al (2001) NMR indirect detection of glutamate to measure citric acid cycle flux in the isolated perfused mouse heart. FEBS Lett 505:163–167

    PubMed  CAS  Google Scholar 

  78. Perdigoto R, Furtado AL, Porto A et al (2003) Sources of glucose production in cirrhosis by 2H2O ingestion and 2H NMR analysis of plasma glucose. Biochim Biophys Acta 1637:156–163

    PubMed  CAS  Google Scholar 

  79. Kikuchi J, Shinozaki K, Hirayama T (2004) Stable isotope labeling of Arabidopsis thaliana for an NMR-based metabolomics approach. Plant Cell Physiol 45:1099–1104

    PubMed  CAS  Google Scholar 

  80. Lane AN, Fan TW, Higashi RM (2008) Isotopomer based metabolic analysis by NMR and mass spectrometry. Biophys Tools Biol 84:541–588

    CAS  Google Scholar 

  81. Lane AN, Fan TW, Xie Z et al (2009) Isotopomer analysis of lipid biosynthesis by high resolution mass spectrometry and NMR. Anal Chim Acta 651:201–208

    PubMed  CAS  Google Scholar 

  82. Coles NW, Johnstone RM (1962) Glutamine metabolism in Ehrlich ascites-carcinoma cells. Biochem J J83:284–291

    Google Scholar 

  83. Eagle H (1955) Nutrition needs of mammalian cells in tissue culture. Science 122:501–514

    PubMed  CAS  Google Scholar 

  84. Wise DR, DeBerardinis RJ, Mancuso A et al (2008) Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci USA 105:18782–18787

    PubMed  CAS  Google Scholar 

  85. Weis BC, Margolis D, Burgess SC et al (2004) Glucose production pathways by 2H and 13C NMR in patients with HIV-associated lipoatrophy. Magn Reson Med 51:649–654

    PubMed  CAS  Google Scholar 

  86. Jones JG, Solomon MA, Cole SM et al (2001) An integrated (2)H and (13)C NMR study of gluconeogenesis and TCA cycle flux in humans. Am J Physiol Endocrinol Metab 281:E848–E856

    PubMed  CAS  Google Scholar 

  87. Hausler N, Browning J, Merritt M et al (2006) Effects of insulin and cytosolic redox state on glucose production pathways in the isolated perfused mouse liver measured by integrated 2H and 13C NMR. Biochem J 394(Pt 2):465–473, Erratum in: Biochem J 2006; 395:663

    PubMed  CAS  Google Scholar 

  88. Perdigoto R, Rodrigues TB, Furtado AL et al (2003) Integration of [U-13C]glucose and 2H2O for quantification of hepatic glucose production and gluconeogenesis. NMR Biomed 16:189–198

    PubMed  CAS  Google Scholar 

  89. Jin ES, Jones JG, Merritt M et al (2004) Glucose production, gluconeogenesis, and hepatic tricarboxylic acid cycle fluxes measured by nuclear magnetic resonance analysis of a single glucose derivative. Anal Biochem 327:149–155

    PubMed  CAS  Google Scholar 

  90. Burgess SC, Weis B, Jones JG et al (2003) Noninvasive evaluation of liver metabolism by 2H and 13C NMR isotopomer analysis of human urine. Anal Biochem 312:228–234

    PubMed  CAS  Google Scholar 

  91. Merritt ME, Harrison C, Sherry AD et al (2011) Flux through hepatic pyruvate carboxylase and phosphoenolpyruvatecarboxykinase detected by hyperpolarized 13C magnetic resonance. Proc Natl Acad Sci USA 108:19084–19089

    PubMed  CAS  Google Scholar 

  92. Schroeder MA, Atherton HJ, Ball DR et al (2009) Real-time assessment of Krebs cycle metabolism using hyperpolarized 13C magnetic resonance spectroscopy. FASEB J 23:2529–2538

    PubMed  CAS  Google Scholar 

  93. Lewis IA, Karsten RH, Norton ME et al (2010) NMR method for measuring carbon-13 isotopic enrichment of metabolites in complex solutions. Anal Chem 82:4558–4563

    PubMed  CAS  Google Scholar 

  94. Fernie AR, Trethewey RN, Krotzky AJ et al (2004) Metabolite profiling: from diagnostics to systems biology. Nat Rev Mol Cell Biol 5:763–769

    PubMed  CAS  Google Scholar 

  95. Shanaiah N, Desilva A, Nagana Gowda GA et al (2007) Metabolite class selection of amino acids in biofluids using chemical derivatization and their enhanced 13C NMR. Proc Natl Acad Sci USA 104:11540–11544

    PubMed  CAS  Google Scholar 

  96. Ye T, Mo H, Shanaiah N et al (2009) Chemoselective 15N tag for sensitive and high-resolution nuclear magnetic resonance profiling of the carboxyl-containing metabolome. Anal Chem 81:4882–4888

    PubMed  CAS  Google Scholar 

  97. Ye T, Zhang S, Mo H et al (2010) 13C-formylation for improved NMR profiling of amino metabolites in biofluids. Anal Chem 82:2303–2309

    PubMed  CAS  Google Scholar 

  98. DeSilva MA, Shanaiah N, Nagana Gowda GA et al (2009) Application of 31P NMR spectroscopy and chemical derivatization for metabolite profiling of lipophilic compounds in human serum. Magn Reson Chem 47:S74–S80

    PubMed  CAS  Google Scholar 

  99. NaganaGowda GA, Tayyari F, Ye T et al (2010) Quantitative analysis of blood plasma metabolites using isotope enhanced NMR methods. Anal Chem 82:8983–8990

    Google Scholar 

  100. Fan TW (1996) Metabolite profiling by one- and two-dimensional NMR analysis of complex mixtures. Prog NMR Spectrosc 28:161–219

    CAS  Google Scholar 

  101. Hu K, Ellinger JJ, Chylla RA et al (2011) Measurement of absolute concentrations of individual compounds in metabolite mixtures by gradient-selective time-zero (1)H-(13)C HSQC with two concentration references and fast maximum likelihood reconstruction analysis. Anal Chem 83:9352–9360

    PubMed  CAS  Google Scholar 

  102. Hu K, Wyche TP, Bugni TS et al (2011) Selective quantification by 2D HSQC(0) spectroscopy of thiocoraline in an extract from a sponge-derived Verrucosispora sp. J Nat Prod 74:2295–2298

    PubMed  CAS  Google Scholar 

  103. Berg JM, Tymoczko JL, Stryer L (2002) Biochemistry. W. H. Freeman & Co, New York

    Google Scholar 

  104. Sakami W, Harrington H (1963) Amino acid metabolism. Annu Rev Biochem 32:355–398

    PubMed  CAS  Google Scholar 

  105. Brosnan JT (2000) Glutamate, at the interface between amino acid and carbohydrate metabolism. J Nutr 130:988S–990S

    PubMed  CAS  Google Scholar 

  106. Young VR, Ajami AM (2001) Glutamine: the emperor or his clothes? J Nutr 131:2449S–2459S

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Anesthesiology and Pain Medicine, Mitochondria and Metabolism Center, University of Washington, Seattle, WA, 98109, USA

    G. A. Nagana Gowda, Narasimhamurthy Shanaiah & Daniel Raftery

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  1. G. A. Nagana Gowda
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  2. Narasimhamurthy Shanaiah
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  3. Daniel Raftery
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Correspondence to G. A. Nagana Gowda .

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  1. , NMR Research Centre, Indian Institute of Science, Bangalore, India

    Hanudatta S. Atreya

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Gowda, G.A.N., Shanaiah, N., Raftery, D. (2012). Isotope Enhanced Approaches in Metabolomics. In: Atreya, H. (eds) Isotope labeling in Biomolecular NMR. Advances in Experimental Medicine and Biology, vol 992. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4954-2_8

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