Skip to main content
SpringerLink
Log in
Book cover

NMR-Based Metabolomics pp 3–14Cite as

Overview of NMR Spectroscopy-Based Metabolomics: Opportunities and Challenges

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2037))

Abstract

The fast-growing field of metabolomics is impacting numerous areas of basic and life sciences. In metabolomics, analytical methods play a pivotal role, and nuclear magnetic resonance (NMR) and mass spectrometry (MS) have proven to be the most suitable and powerful methods. Although NMR exhibits lower sensitivity and resolution compared to MS, NMR’s numerous important characteristics far outweigh its limitations. Some of its characteristics include excellent reproducibility and quantitative accuracy, the capability to analyze intact biospecimens, an unparalleled ability to identify unknown metabolites, the ability to trace in-cell and in-organelle metabolism in real time, and the capacity to trace metabolic pathways atom by atom using 2H, 13C, or 15N isotopes. Each of these characteristics has been exploited extensively in numerous studies. In parallel, the field has witnessed significant progress in instrumentation, methods development, databases, and automation that are focused on higher throughput and alleviating the limitations of NMR, in particular, resolution and sensitivity. Despite the advances, however, the high complexity of biological mixtures combined with the limitations in sensitivity and resolution continues to pose major challenges. These challenges need to be dealt with effectively to better realize the potential of metabolomics, in general. As a result, multifaceted efforts continue to focus on addressing the challenges as well as reaping the benefits of NMR-based metabolomics. This chapter highlights the current status with emphasis on the opportunities and challenges in NMR-based metabolomics.

This is a preview of subscription content, log in via an institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Antic T, DeMay RM (2014) The fascinating history of urine examination. J Am Soc Cytopathol 3:103e107

    Article  Google Scholar 

  2. Bhishagratna KKL (1911) An English translation of “The Sushruta Samhita”, vol II. The Bharat Mihir Press, Calcutta

    Google Scholar 

  3. Jacob R (2015) Sickening sweet. Distillations 1(4):12–15

    Google Scholar 

  4. Das S (2001) Susruta, the pioneer urologist of antiquity. J Urol 165(5):1405–1408

    Article  CAS  PubMed  Google Scholar 

  5. Karamanou M, Protogerou A, Tsoucalas G, Androutsos G, Poulakou-Rebelakou E (2016) Milestones in the history of diabetes mellitus: the main contributors. World J Diabetes 7(1):1–7

    Article  PubMed  PubMed Central  Google Scholar 

  6. Williams RJ et al (1951) Individual metabolic patterns and human disease: an exploratory study utilizing predominantly paper chromatographic methods. Biochemical Institute Studies IV, University of Texas Publication No. 5109, University of Texas, Austin, 204 pp

    Google Scholar 

  7. Gates SC, Sweeley CC (1978) Quantitative metabolic profiling based on gas chromatography. Clin Chem 24(10):1663–1673

    CAS  PubMed  Google Scholar 

  8. Nagana Gowda GA, Djukovic D (2014) Overview of mass spectrometry-based metabolomics: opportunities and challenges. Methods Mol Biol 1198:3–12

    Article  CAS  Google Scholar 

  9. Pauling L, Robinson AB, Teranishi R, Cary P (1971) Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. Proc Natl Acad Sci U S A 68(10):2374–2376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bloch F, Hansen WW, Packard M (1946) Nuclear induction. Phys Rev 69:127

    Article  Google Scholar 

  11. Purcell EM, Torrey HC, Pound RV (1946) Resonance absorption by nuclear magnetic moments in a solid. Phys Rev 69:37–38

    Article  CAS  Google Scholar 

  12. Becker ED (1993) A brief history of nuclear magnetic resonance. Anal Chem 65(6):295A–302A

    Article  CAS  PubMed  Google Scholar 

  13. Hoult DI, Busby SJ, Gadian DG, Radda GK, Richards RE, Seeley PJ (1974) Observation of tissue metabolites using 31P nuclear magnetic resonance. Nature 252(5481):285–287

    Article  CAS  PubMed  Google Scholar 

  14. Navon G, Ogawa S, Shulman RG, Yamane T (1977) High-resolution 31P nuclear magnetic resonance studies of metabolism in aerobic Escherichia coli cells. Proc Natl Acad Sci U S A 74(3):888–891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Navon G, Ogawa S, Shulman RG, Yamane T (1977) 31P nuclear magnetic resonance studies of Ehrlich ascites tumor cells. Proc Natl Acad Sci U S A 74(1):87–91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Burt CT, Glonek T, Barany M (1976) Analysis of phosphate metabolites, the intracellular pH, and the state of adenosine triphosphate in intact muscle by phosphorus nuclear magnetic resonance. J Biol Chem 251:2584–2591

    CAS  PubMed  Google Scholar 

  17. Henderson TO, Costello AJR, Omachi A (1974) Phosphate metabolism in intact human erythrocytes: determination by phosphorus-31 nuclear magnetic resonance spectroscopy. Proc Natl Acad Sci U S A 71:2487–2490

    Article  PubMed  PubMed Central  Google Scholar 

  18. Moon RB, Richards JH (1973) Determination of intracellular pH by 31P magnetic resonance. J Biol Chem 248:7276–7278

    CAS  PubMed  Google Scholar 

  19. Salhany JM, Yamane T, Shulman RG, Ogawa S (1975) High resolution 31P nuclear magnetic resonance studies of intact yeast cells. Proc Natl Acad Sci U S A 72:4966–4970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nicholson JK, Wilson ID (1989) High resolution proton magnetic resonance spectroscopy of biological fluids. Prog Nucl Magn Reson Spectrosc 21(4–5):449–501

    Article  CAS  Google Scholar 

  21. Nagana Gowda GA, Gowda YN, Raftery D (2015) Expanding the limits of human blood metabolite quantitation using NMR spectroscopy. Anal Chem 87(1):706–715

    Article  CAS  PubMed  Google Scholar 

  22. Nagana Gowda GA, Abell L, Lee CF, Tian R (2016) Raftery D (2016) simultaneous analysis of major coenzymes of cellular redox reactions and energy using ex vivo (1)H NMR spectroscopy. Anal Chem 88(9):4817–4824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Nagana Gowda GA, Abell L, Lee CF, Tian R (2019) Extending the scope of 1H NMR spectroscopy for the analysis of cellular coenzyme A and acetyl coenzyme A. Anal Chem 91(3):2464–2471

    Article  CAS  PubMed  Google Scholar 

  24. Nagana Gowda GA, Raftery D (2017) Recent advances in NMR-based metabolomics. Anal Chem 89(1):490–510

    Article  CAS  PubMed  Google Scholar 

  25. Leenders J, Frédérich M, de Tullio P (2015) Nuclear magnetic resonance: a key metabolomics platform in the drug discovery process. Drug Discov Today Technol 13:39–46

    Article  PubMed  Google Scholar 

  26. Johanningsmeier SD, Harris GK, Klevorn CM (2016) Metabolomic technologies for improving the quality of food: practice and promise. Annu Rev Food Sci Technol 7:413–438

    Article  CAS  PubMed  Google Scholar 

  27. Sumner LW, Lei Z, Nikolau BJ, Saito K (2015) Modern plant metabolomics: advanced natural product gene discoveries, improved technologies, and future prospects. Nat Prod Rep 32:212–229

    Article  CAS  PubMed  Google Scholar 

  28. Mahrous EA, Farag MA (2015) Two dimensional NMR spectroscopic approaches for exploring plant metabolome: a review. J Adv Res 6(1):3–15

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  31. Lane AN, Fan TW, Bousamra M 2nd, Higashi RM, Yan J, Miller DM (2011) Stable isotope-resolved metabolomics (SIRM) in cancer research with clinical application to nonsmall cell lung cancer. OMICS 15(3):173–182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mashimo T, Pichumani K, Vemireddy V, Hatanpaa KJ, Singh DK, Sirasanagandla S et al (2014) Acetate is a bioenergetic substrate for human glioblastoma and brain metastases. Cell 159(7):1603–1614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wen H, An YJ, Xu WJ, Kang KW, Park S (2015) Real-time monitoring of cancer cell metabolism and effects of an anticancer agent using 2D in-cell NMR spectroscopy. Angew Chem Int Ed Engl 54(18):5374–5377

    Article  CAS  PubMed  Google Scholar 

  34. Xu WJ, Wen H, Kim HS, Ko YJ, Dong SM, Park IS, Yook JI, Park S (2018) Observation of acetyl phosphate formation in mammalian mitochondria using real-time in-organelle NMR metabolomics. Proc Natl Acad Sci U S A 115(16):4152–4157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kc R, Henry ID, Park GH, Aghdasi A, Raftery D (2010) New solenoidal microcoil NMR probe using zero-susceptibility wire. Concepts Magn Reson Part B Magn Reson Eng 37B(1):13–19

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Grimes JH, O’Connell TM (2011) The application of micro-coil NMR probe technology to metabolomics of urine and serum. J Biomol NMR 49:297–305

    Article  CAS  PubMed  Google Scholar 

  37. Bird SS, Sheldon DP, Gathungu RM, Vouros P, Kautz R, Matson WR et al (2012) Structural characterization of plasma metabolites detected via LC-electrochemical coulometric array using LC-UV fractionation, MS, and NMR. Anal Chem 84:9889–9898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cloarec O, Campbell A, Tseng LH, Braumann U, Spraul M, Scarfe G et al (2007) Virtual chromatographic resolution enhancement in cryoflow LC-NMR experiments via statistical total correlation spectroscopy. Anal Chem 79:3304–3311

    Article  CAS  PubMed  Google Scholar 

  39. Lenz EM, Wilson ID (2007) Analytical strategies in metabonomics. J Proteome Res 6:443–458

    Article  CAS  PubMed  Google Scholar 

  40. Djukovic D, Liu S, Henry I, Tobias B, Raftery D (2006) Signal enhancement in HPLC/microcoil NMR using automated column trapping. Anal Chem 78:7154–7160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Djukovic D, Appiah-Amponsah E, Shanaiah N, Nagana Gowda GA, Henry I, Everly M et al (2008) Ibuprofen metabolite profiling using a combination of SPE/column-trapping and HPLC-micro-coil NMR. J Pharm Biomed Anal 47:328–334

    Article  CAS  PubMed  Google Scholar 

  42. Garcia E, Andrews C, Hua J, Kim HL, Sukumaran DK, Szyperski T et al (2011) Diagnosis of early stage ovarian cancer by 1H NMR metabonomics of serum explored by use of a microflow NMR probe. J Proteome Res 10:1765–1771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hyberts SG, Heffron GJ, Tarragona NG, Solanky K, Edmonds KA, Luithardt H et al (2007) Ultrahigh-resolution (1)H-(13)C HSQC spectra of metabolite mixtures using nonlinear sampling and forward maximum entropy reconstruction. J Am Chem Soc 129(16):5108–5116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hyberts SG, Arthanari H, Wagner G (2012) Applications of non-uniform sampling and processing. Top Curr Chem 316:125–148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Rai RK, Sinha N (2012) Fast and accurate quantitative metabolic profiling of body fluids by nonlinear sampling of 1H–13C two-dimensional nuclear magnetic resonance spectroscopy. Anal Chem 84(22):10005–10011

    Article  CAS  PubMed  Google Scholar 

  46. Motta A, Paris D, Melck D (2010) Monitoring real-time metabolism of living cells by fast two-dimensional NMR spectroscopy. Anal Chem 82(6):2405–2411

    Article  CAS  PubMed  Google Scholar 

  47. Bruschweiler R, Zhang F (2004) Covariance nuclear magnetic resonance spectroscopy. J Chem Phys 120:5253–5260

    Article  CAS  PubMed  Google Scholar 

  48. Frydman L, Scherf T, Lupulescu A (2002) The acquisition of multidimensional NMR spectra within a single scan. Proc Natl Acad Sci U S A 99:15858–15862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Giraudeau P, Remaud GS, Akoka S (2009) Evaluation of ultrafast 2D NMR for quantitative analysis. Anal Chem 81(1):479–484

    Article  CAS  PubMed  Google Scholar 

  50. Bhattacharya P, Chekmenev EY, Perman WH, Harris KC, Lin AP, Norton VA et al (2007) Towards hyperpolarized (13)C-succinate imaging of brain cancer. J Magn Reson 186:150–155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Shchepin RV, Coffey AM, Waddell KW, Chekmenev EY (2012) PASADENA hyperpolarized 13C phospholactate. J Am Chem Soc 134(9):3957–3960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ardenkjaer-Larsen JH, Fridlund B, Gram A, Hansson G, Hansson L, Lerche MH et al (2003) Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR. Proc Natl Acad Sci U S A 100(18):10158–10163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Girard DA (1989) A fast ‘Monte-Carlo cross-validation’ procedure for large least squares problems with noisy data. Numer Math 56(1):1–23

    Article  Google Scholar 

  54. Chen C, Deng L, Wei S, Nagana Gowda GA, Gu H, Chiorean EG et al (2015) Exploring metabolic profile differences between colorectal polyp patients and controls using seemingly unrelated regression. J Proteome Res 14(6):2492–2499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chen C, Nagana Gowda GA, Zhu J, Deng L, Gu H, Chiorean EG et al (2017) Altered metabolite levels and correlations in patients with colorectal cancer and polyps detected using seemingly unrelated regression analysis. Metabolomics 13:125. https://doi.org/10.1007/s11306-017-1265-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Maciejewski MW, Schuyler AD, Gryk MR, Moraru II, Romero PR, Ulrich EL et al (2017) NMRbox: a resource for biomolecular NMR computation. Biophys J 112(8):1529–1534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Nagana Gowda GA, Raftery D (2015) Can NMR solve some significant challenges in metabolomics? J Magn Reson 260:144–160

    Article  CAS  PubMed  Google Scholar 

  58. Sud M, Fahy E, Cotter D, Azam K, Vadivelu I, Burant C et al (2016) Metabolomics workbench: an international repository for metabolomics data and metadata, metabolite standards, protocols, tutorials and training, and analysis tools. Nucleic Acids Res 44(D1):D463–D470

    Article  CAS  PubMed  Google Scholar 

  59. Kale NS, Haug K, Conesa P, Jayseelan K, Moreno P, Rocca-Serra P et al (2016) MetaboLights: an open-access database repository for metabolomics data. Curr Protoc Bioinformatics 53:14.13.1–14.13.18

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Northwest Metabolomics Research Center, University of Washington, Seattle, WA, USA

    G. A. Nagana Gowda & Daniel Raftery

  2. Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA

    G. A. Nagana Gowda & Daniel Raftery

  3. Mitochondria and Metabolism Center, University of Washington, Seattle, WA, USA

    G. A. Nagana Gowda & Daniel Raftery

  4. Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Daniel Raftery

Authors
  1. G. A. Nagana Gowda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Raftery
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniel Raftery .

Editor information

Editors and Affiliations

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

    G. A. Nagana Gowda

  2. Northwest Metabolomics Research Center, Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Fred Hutch Cancer Research Center, Seattle, WA, USA

    Daniel Raftery

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Nagana Gowda, G.A., Raftery, D. (2019). Overview of NMR Spectroscopy-Based Metabolomics: Opportunities and Challenges. In: Gowda, G., Raftery, D. (eds) NMR-Based Metabolomics. Methods in Molecular Biology, vol 2037. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9690-2_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9690-2_1

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9689-6

  • Online ISBN: 978-1-4939-9690-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation