Skip to main content
SpringerLink
Log in

Quantitative NMR Methods in Metabolomics

  • Chapter
  • First Online:
Metabolomics and Its Impact on Health and Diseases

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 277))

Abstract

Nuclear Magnetic Resonance (NMR) spectroscopy is one of the two major analytical platforms in the field of metabolomics, the other being mass spectrometry (MS). NMR is less sensitive than MS and hence it detects a relatively small number of metabolites. However, NMR exhibits numerous unique characteristics including its high reproducibility and non-destructive nature, its ability to identify unknown metabolites definitively, and its capabilities to obtain absolute concentrations of all detected metabolites, sometimes even without an internal standard. These characteristics outweigh the relatively low sensitivity and resolution of NMR in metabolomics applications. Since biological mixtures are highly complex, increased demand for new methods to improve detection, better identify unknown metabolites, and provide more accurate quantitation continues unabated. Technological and methodological advances to date have helped to improve the resolution and sensitivity and detection of a larger number of metabolite signals. Efforts focused on measuring unknown metabolite signals have resulted in the identification and quantitation of an expanded pool of metabolites including labile metabolites such as cellular redox coenzymes, energy coenzymes, and antioxidants. This chapter describes quantitative NMR methods in metabolomics with an emphasis on recent methodological developments, while highlighting the benefits and challenges of NMR-based metabolomics.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
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 169.99
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

Institutional subscriptions

References

  • Airoldi C, Tripodi F, Guzzi C, Nicastro R, Coccetti P (2015) NMR analysis of budding yeast metabolomics: a rapid method for sample preparation. Mol Biosyst 11(2):379–383

    Article  CAS  PubMed  Google Scholar 

  • Akoka S, Barantin L, Trierweiler M (1999) Concentration measurement by proton NMR using the ERETIC method. Anal Chem 71(13):2554–2557

    Article  CAS  PubMed  Google Scholar 

  • Albrecht B, Voronina E, Schipke C, Peters O, Parr MK, Díaz-Hernández MD, Schlörer NE (2020) Pursuing experimental reproducibility: an efficient protocol for the preparation of cerebrospinal fluid samples for NMR-based metabolomics and analysis of sample degradation. Metabolites 10(6):251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alum MF, Shaw PA, Sweatman BC, Ubhi BK, Haselden JN, Connor SC (2008) 4,4-Dimethyl-4-silapentane-1-ammonium trifluoroacetate (DSA), a promising universal internal standard for NMR-based metabolic profiling studies of biofluids, including blood plasma and serum. Metabolomics 4:122–127

    Article  CAS  Google Scholar 

  • Anderson JR, Phelan MM, Rubio-Martinez LM, Fitzgerald MM, Jones SW, Clegg PD, Peffers MJ (2020) Optimization of synovial fluid collection and processing for NMR metabolomics and LC-MS/MS proteomics. J Proteome Res 19(7):2585–2597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bala L, Ghoshal UC, Ghoshal U, Tripathi P, Misra A, Nagana Gowda GA, Khetrapal CL (2006) Malabsorption syndrome with and without small intestinal bacterial overgrowth: a study on upper-gut aspirate using 1H NMR spectroscopy. Magn Reson Med 56(4):738–744

    Article  PubMed  Google Scholar 

  • Barding GA Jr, Salditos R, Larive CK (2012) Quantitative NMR for bioanalysis and metabolomics. Anal Bioanal Chem 404(4):1165–1179

    Article  CAS  PubMed  Google Scholar 

  • Barrilero R, Gil M, Amigó N, Dias CB, Wood LG, Garg ML et al (2018) LipSpin: a new bioinformatics tool for quantitative 1 H NMR lipid profiling. Anal Chem 90:2031–2040

    Article  CAS  PubMed  Google Scholar 

  • Beckonert O, Keun HC, Ebbels TM, Bundy J, Holmes E, Lindon JC, Nicholson JK (2007) Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat Protoc 2(11):2692–2703

    Article  CAS  PubMed  Google Scholar 

  • Bell JD, Brown JC, Kubal G, Sadler PJ (1988) NMR-invisible lactate in blood plasma. FEBS Lett 235:81–86

    Article  CAS  PubMed  Google Scholar 

  • Bingol K, Zhang F, Bruschweiler-Li L, Brüschweiler R (2012) Carbon backbone topology of the metabolome of a cell. J Am Chem Soc 134:9006–9011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bingol K, Zhang F, Bruschweiler-Li L, Brüschweiler R (2013) Quantitative analysis of metabolic mixtures by two-dimensional 13C constant-time TOCSY NMR spectroscopy. Anal Chem 85:6414–6420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37(8):911–917

    Article  CAS  PubMed  Google Scholar 

  • Bouatra S, Aziat F, Mandal R, Guo AC, Wilson MR, Knox C, Bjorndahl TC et al (2013) The human urine metabolome. Plos One 8(9):e73076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chatham JC, Forder JR (1999) Lactic acid and protein interactions: implications for the NMR visibility of lactate in biological systems. Biochim Biophys Acta 1426(1):177–184

    Article  CAS  PubMed  Google Scholar 

  • Chen W, Lu S, Wang G, Chen F, Bai C (2017) Staging research of human lung cancer tissues by high-resolution magic angle spinning proton nuclear magnetic resonance spectroscopy (HRMAS 1 H NMR) and multivariate data analysis. Asia Pac J Clin Oncol 13(5):e232–e238

    Article  PubMed  Google Scholar 

  • Chikayama E, Suto M, Nishihara T, Shinozaki K, Kikuchi J (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

    Article  PubMed  PubMed Central  Google Scholar 

  • Choi JS, Baek HM, Kim S, Kim MJ, Youk JH, Moon HJ, Kim EK et al (2012) HR-MAS MR spectroscopy of breast cancer tissue obtained with core needle biopsy: correlation with prognostic factors. PLoS One 7:e51712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cruz M, Wang M, Frisch-Daiello J, Han X (2016) Improved butanol-methanol (BUME) method by replacing acetic acid for lipid extraction of biological samples. Lipids 51(7):887–896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • d'Alessandro A, Osterloh JD, Chuwers P, Quinlan PJ, Kelly TJ, Becker CE (1994) Formate in serum and urine after controlled methanol exposure at the threshold limit value. Environ Health Perspect 102(2):178–181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daykin CA, Foxall PJ, Connor SC et al (2002) The comparison of plasma deproteinization methods for the detection of low-molecular-weight metabolites by (1)H nuclear magnetic resonance spectroscopy. Anal Biochem 304(2):220–230

    Article  CAS  PubMed  Google Scholar 

  • DeSilva MA, Shanaiah N, Nagana Gowda GA, Raftery MA, Hainline BE, Raftery D (2009) Application of 31P NMR spectroscopy and chemical derivatization for metabolite profiling of lipophilic compounds in human serum. Magn Reson Chem 47Suppl 1:S74–S80

    Article  Google Scholar 

  • Dinges SS, Vandergrift LA, Wu S, Berker Y, Habbel P, Taupitz M, Wu C-L et al (2019) Metabolomic prostate cancer fields in HRMAS MRS-profiled histologically benign tissue vary with cancer status and distance from cancer. NMR Biomed 32(10):e4038

    Article  PubMed  PubMed Central  Google Scholar 

  • Djukovic D, Raftery D, Nagana Gowda GA (2020) Chapter 16 – Mass spectrometry and NMR spectroscopy based quantitative metabolomics. In: Issaq HJ, Veenstra TD (eds) Proteomic and metabolomic approaches to biomarker discovery, 2nd edn. Academic Press, pp 289–311

    Chapter  Google Scholar 

  • Edison S, Colonna M, Gouveia GJ, Holderman NR, Judge MT, Shen X, Zhang S (2021) NMR: unique strengths that enhance modern metabolomics research. Anal Chem 93:478

    Article  CAS  PubMed  Google Scholar 

  • Emwas AH, Luchinat C, Turano P et al (2015) Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review. Metabolomics 11(4):872–894

    Article  CAS  PubMed  Google Scholar 

  • Emwas AH, Roy R, McKay RT, Ryan D, Brennan L, Tenori L, Luchinat C, Gao X, Zeri AC, Nagana Gowda GA, Raftery D, Steinbeck C, Salek RM, Wishart DS (2016) Recommendations and standardization of biomarker quantification using NMR-based metabolomics with particular focus on urinary analysis. J Proteome Res 15(2):360–373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Engel KM, Baumann S, Rolle-Kampczyk U, Schiller J, von Bergen M, Grunewald S (2019) Metabolomic profiling reveals correlations between spermiogram parameters and the metabolites present in human spermatozoa and seminal plasma. PLoS One 14(2):e0211679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Evans C, Bogan KL, Song P, Burant CF, Kennedy RT, Brenner C (2010) NAD+ metabolite levels as a function of vitamins and calorie restriction: evidence for different mechanisms of longevity. BMC Chem Biol 10:2

    Article  PubMed  PubMed Central  Google Scholar 

  • Fan TW (2012) In: Fan TW, Higashi RM, Lane AN (eds) The handbook of metabolomics, methods in pharmacology and toxicology, vol 2012. Springer, New York, pp 7–27

    Chapter  Google Scholar 

  • Fan TW, Lane AN, Higashi RM, Farag MA, Gao H, Bousamra M, Miller DH (2009) Altered regulation of metabolic pathways in human lung cancer discerned by (13)C stable isotope-resolved metabolomics (SIRM). Mol Cancer 8:41

    Article  PubMed  PubMed Central  Google Scholar 

  • Folch J, Lees M, Stanley G (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:497–509

    Article  CAS  PubMed  Google Scholar 

  • Gil M, Samino S, Barrilero R, Correig X (2019) Lipid profiling using 1 H NMR spectroscopy. Methods Mol Biol 2037:35–47

    Article  CAS  PubMed  Google Scholar 

  • Goldman A, Khiste S, Freinkman E, Dhawan A, Majumder B, Mondal J, Pinkerton AB, Eton E, Medhi R, Chandrasekar V, Rahman MM, Ichimura T, Gopinath KS, Majumder P, Kohandel M, Sengupta S (2019) Targeting tumor phenotypic plasticity and metabolic remodeling in adaptive crossdrug tolerance. Sci Signal 12(595):eaas8779. https://doi.org/10.1126/scisignal.aas8779

  • Goldoni L, Beringhelli T, Rocchia W, Realini N, Piomelli D (2016) A simple and accurate protocol for absolute polar metabolite quantification in cell cultures using quantitative nuclear magnetic resonance. Anal Biochem 501:26–34

    Article  CAS  PubMed  Google Scholar 

  • Hernandez ME, Lopez AC, Calatayud AG et al (2001) Vesical uric acid lithiasis in a child with renal hypouricemia. An Esp Pediatr 55(3):273–276

    Google Scholar 

  • Holzgrabe U (2010) Quantitative NMR spectroscopy in pharmaceutical applications. Prog Nucl Magn Reson Spectrosc 57(2):229–240

    Article  CAS  PubMed  Google Scholar 

  • Hoult DI (2000) The principle of reciprocity in signal strength calculations – a mathematical guide. Concepts Magn Reson 12:173–187

    Article  CAS  Google Scholar 

  • Hoult DI, Richards RE (1976) The signal-to-noise ratio of the nuclear magnetic resonance experiment. J Magn Reson 24:71–85

    Google Scholar 

  • Ivanisevic J, Zhu ZJ, Plate L, Tautenhahn R, Chen S, O'Brien PJ, Johnson CH, Marletta MA, Patti GJ, Siuzdak G (2013) Toward 'omic scale metabolite profiling: a dual separation-mass spectrometry approach for coverage of lipid and central carbon metabolism. Anal Chem 85(14):6876–6884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeyarajah EJ, Cromwell WC, Otvos JD (2006) Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy. Clin Lab Med 26:847–870

    Article  PubMed  Google Scholar 

  • Jiménez B, Holmes E, Heude C, Tolson RF, Harvey N, Lodge SL, Chetwynd AJ et al (2018) Quantitative lipoprotein subclass and low molecular weight metabolite analysis in human serum and plasma by 1H NMR spectroscopy in a multilaboratory trial. Anal Chem 90(20):11962–11971

    Article  PubMed  Google Scholar 

  • Johnson CS (1999) Diffusion ordered nuclear magnetic resonance spectroscopy: principles and applications. Prog Nucl Magn Reson Spectrosc 34:203–256

    Article  CAS  Google Scholar 

  • Johnson CH, Ivanisevic J, Siuzdak G (2016) Metabolomics: beyond biomarkers and towards mechanisms. Nat Rev Mol Cell Biol 17:451–459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaess B, Fischer M, Baessler A, Stark K, Huber F, Kremer W, Kalbitzer HR et al (2008) The lipoprotein subfraction profile: heritability and identification of quantitative trait loci. J Lipid Res 49:715–723

    Article  CAS  PubMed  Google Scholar 

  • Kalfe A, Telfah A, Lambert J, Hergenröder R (2015) Looking into living cell systems: planar waveguide microfluidic NMR detector for in vitro metabolomics of tumor spheroids. Anal Chem 87(14):7402–7410

    Article  CAS  PubMed  Google Scholar 

  • Kapur BM, Vandenbroucke AC, Adamchik Y, Lehotay DC, Carlen PL (2007) Formic acid, a novel metabolite of chronic ethanol abuse, causes neurotoxicity, which is prevented by folic acid. Alcohol Clin Exp Res 31(12):2114–2120

    Article  CAS  PubMed  Google Scholar 

  • Kodama M, Oshikawa K, Shimizu H, Yoshioka S, Takahashi M, Izumi Y, Bamba T, Tateishi C, Tomonaga T, Matsumoto M, Nakayama KI (2020) A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer. Nat Commun 11:1320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kriat M, Confort-Gouny S, Vion-Dury J, Sciaky M, Viout P, Cozzone PJ (1992) Quantitation of metabolites in human blood serum by proton magnetic resonance spectroscopy. A comparative study of the use of formate and TSP as concentration standards. NMR Biomed 5(4):179–184

    Article  CAS  PubMed  Google Scholar 

  • Kubáň P, Boček P (2013) Direct analysis of formate in human plasma, serum and whole blood by in-line coupling of microdialysis to capillary electrophoresis for rapid diagnosis of methanol poisoning. Anal Chim Acta 768:82–89

    Article  PubMed  Google Scholar 

  • Lane AN, Fan TW, Bousamra M II, Higashi RM, Yan J, Milleret DM (2011) Stable isotope-resolved metabolomics (SIRM) in cancer research with clinical application to NonSmall cell lung cancer OMICS. J Integr Biol 15:173–182

    CAS  Google Scholar 

  • Lane AN, Tan J, Wang Y et al (2017) Probing the metabolic phenotype of breast cancer cells by multiple tracer stable isotope resolved metabolomics. Metab Eng 43(Pt B):125–136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin P, Lane AN, Fan TW (2019) Stable isotope-resolved metabolomics by NMR. Methods Mol Biol 2037:151–168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Locasale JW, Grassian AR, Melman T, Lyssiotis CA, Mattaini KR, Bass AJ, Heffron G et al (2011) Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat Genet 43:869–874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Löfgren L, Ståhlman M, Forsberg GB, Saarinen S, Nilsson R, Hansson GI (2012) The BUME method: a novel automated chloroform-free 96-well total lipid extraction method for blood plasma. J Lipid Res 53:1690–1700

    Article  PubMed  PubMed Central  Google Scholar 

  • Lohavanichbutr P, Zhang Y, Wang P, Gu H, Nagana Gowda GA, Djukovic D, Buas MF, Raftery D, Chen C (2018) Salivary metabolite profiling distinguishes patients with oral cavity squamous cell carcinoma from normal controls. PLoS One 13(9):e0204249

    Article  PubMed  PubMed Central  Google Scholar 

  • Lucas LH, Larive CK, Wilkinson PS, Huhn S (2005) Progress toward automated metabolic profiling of human serum: comparison of CPMG and gradient-filtered NMR analytical methods. J Pharm Biomed Anal 39(1–2):156–163

    Article  CAS  PubMed  Google Scholar 

  • Lussu M, Camboni T, Piras C, Serra C, Del Carratore F, Griffin J, Atzori L, Manzin A (2017) 1H NMR spectroscopy-based metabolomics analysis for the diagnosis of symptomatic E. coli-associated urinary tract infection (UTI). BMC Microbiol 17(1):201

    Google Scholar 

  • Mallol R, Rodriguez MA, Brezmes J, Masana L, Correig X (2013) Human serum/plasma lipoprotein analysis by NMR: application to the study of diabetic dyslipidemia. Prog Nucl Magn Reson Spectrosc 70:1–24

    Article  CAS  PubMed  Google Scholar 

  • Mallol R, Amigó N, Rodríguez MA, Heras M, Vinaixa M, Plana N, Rock E et al (2015) Liposcale: a novel advanced lipoprotein test based on 2D diffusion-ordered 1H NMR spectroscopy. J Lipid Res 56(3):737–746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maniara G, Rajamoorthi K, Rajan S, Stockton GW (1998) Method performance and validation for quantitative analysis by 1H and 31P NMR spectroscopy. Applications to analytical standards and agricultural chemicals. Anal Chem 70(23):4921–4928

    Article  CAS  PubMed  Google Scholar 

  • Maniscalco M, Cutignano A, Paris D, Melck DJ, Molino A, Fuschillo S, Motta A (2020) Metabolomics of exhaled breath condensate by nuclear magnetic resonance spectroscopy and mass spectrometry: a methodological approach. Curr Med Chem 27(14):2381–2399

    Article  CAS  PubMed  Google Scholar 

  • Mo H, Raftery D (2008) Solvent signal as an NMR concentration reference. Anal Chem 80(24):9835–9839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagana Gowda GA (2011) NMR spectroscopy for discovery and quantitation of biomarkers of disease in human bile. Bioanalysis 3(16):1877–1890

    Article  Google Scholar 

  • Nagana Gowda GA (2018) Profiling redox and energy coenzymes in whole blood, tissue and cells using NMR spectroscopy. Metabolites 8(2):32

    Article  Google Scholar 

  • Nagana Gowda GA, Raftery D (2014a) Advances in NMR based metabolomics. In: Simó C, Cifuentes A, García-Cañas V (eds) Fundamentals of advanced Omics technologies: from genes to metabolites, comprehensive analytical chemistry, vol 63. Elsevier, New York, pp 187–211

    Chapter  Google Scholar 

  • Nagana Gowda GA, Raftery D (2014b) Quantitating metabolites in protein precipitated serum using NMR spectroscopy. Anal Chem 86(11):5433–5440

    Article  CAS  PubMed  Google Scholar 

  • 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 

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

    Article  CAS  PubMed  Google Scholar 

  • Nagana Gowda GA, Raftery D (2017b) Whole blood metabolomics by 1H NMR spectroscopy provides a new opportunity to evaluate coenzymes and antioxidants. Anal Chem 89(8):4620–4627

    Article  CAS  PubMed  Google Scholar 

  • Nagana Gowda GA, Raftery D (eds) (2019) NMR based metabolomics: methods and protocols, Methods in molecular biology, vol 2037. Humana Press/Springer Science, New York

    Google Scholar 

  • 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 

  • Nagana Gowda GA, Abell L, Lee CF, Tian R, 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 

  • Nagana Gowda GA, Djukovic D, Bettcher LF, Gu H, Raftery D (2018) NMR-guided mass spectrometry for absolute quantitation of human blood metabolites. Anal Chem 90(3):2001–2009

    Article  CAS  PubMed  Google Scholar 

  • Nagana Gowda GA, Abell L, 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 

  • Nagana Gowda GA, Hong NN, Raftery D (2021) Evaluation of Fumaric acid and maleic acid as internal standards for NMR analysis of protein precipitated plasma, serum, and whole blood. Anal Chem 93(6):3233–3240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen TTM, An YJ, Cha JW, Ko YJ, Lee H, Chung CH, Jeon SM et al (2020) Real-time in-organism NMR metabolomics reveals different roles of AMP-activated protein kinase catalytic subunits. Anal Chem 92(11):7382–7387

    Article  CAS  PubMed  Google Scholar 

  • Nicholson JK, Gartland KP (1989) 1H NMR studies on protein binding of histidine, tyrosine and phenylalanine in blood plasma. NMR Biomed 2(2):77–82

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Orczyk-Pawilowicz M, Jawien E, Deja S, Hirnle L, Zabek A, Mlynarz P (2016) Metabolomics of human amniotic fluid and maternal plasma during normal pregnancy. PLoS One 11(4):e0152740

    Article  PubMed  PubMed Central  Google Scholar 

  • Paul A, Kumar S, Raj A, Sonkar AA, Jain S, Singhai A, Roy R (2018) Alteration in lipid composition differentiates breast cancer tissues: a 1 H HRMAS NMR metabolomic study. Metabolomics 14(9):119

    Article  PubMed  Google Scholar 

  • Pauli GF, Gödecke T, Jaki BU, Lankin DC (2012) Quantitative 1H NMR. Development and potential of an analytical method: an update. J Nat Prod 75(4):834–851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Psychogios N, Hau DD, Peng J, Guo AC, Mandal R, Bouatra S, Sinelnikov I et al (2011) The human serum metabolome. PLoS One 6(2):e16957

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raftery D (ed) (2014) Mass spectrometry in metabolomics: methods and protocols, Methods in molecular biology, vol 1198. Humana Press/Springer Science, New York

    Google Scholar 

  • Rundlöf T, Mathiasson M, Bekiroglu S, Hakkarainen B, Bowden T, Arvidsson T (2010) Survey and qualification of internal standards for quantification by 1H NMR spectroscopy. J Pharm Biomed Anal 52(5):645–651

    Article  PubMed  Google Scholar 

  • Rylander R, Remer T, Berkemeyer S, Vormann J (2006) Acid–base status affects renal magnesium losses in healthy, elderly persons. J Nutr 136(9):2374–2377

    Article  CAS  PubMed  Google Scholar 

  • Salem AA, Mossa HA (2012) Method validation and determinations of levofloxacin, metronidazole and sulfamethoxazole in an aqueous pharmaceutical, urine and blood plasma samples using quantitative nuclear magnetic resonance spectrometry. Talanta 88:104–114

    Article  CAS  PubMed  Google Scholar 

  • Shanaiah N, Desilva MA, Nagana Gowda GA et al (2007) Class selection of amino acid metabolites in body fluids using chemical derivatization and their enhanced 13C NMR. Proc Natl Acad Sci U S A 104(28):11540–11544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Simón-Manso Y, Lowenthal MS, Kilpatrick LE, Sampson ML, Telu KH, Rudnick PA, Mallard WG et al (2013) Metabolite profiling of a NIST standard reference material for human plasma (SRM 1950): GC-MS, LC-MS, NMR, and clinical laboratory analyses, libraries, and web-based resources. Anal Chem 85(24):11725–11731

    Article  PubMed  Google Scholar 

  • Sitter B, Bathen TF, Singstad TE, Fjøsne HE, Lundgren S, Halgunset J, Gribbestad IS (2010) Quantification of metabolites in breast cancer patients with different clinical prognosis using HR MAS MR spectroscopy. NMR Biomed 23(4):424–431

    Article  CAS  PubMed  Google Scholar 

  • Soininen P, Kangas AJ, Wurtz P, Tukiainen T, Tynkkynen T, Laatikainen R, Jarvelin MR et al (2009) High-throughput serum NMR metabonomics for cost-effective holistic studies on systemic metabolism. Analyst 134:1781–1785

    Article  CAS  PubMed  Google Scholar 

  • Soininen P, Kangas AJ, Würtz P, Suna T, Ala-Korpela M (2015) Quantitative serum nuclear magnetic resonance metabolomics in cardiovascular epidemiology and genetics. Circ Cardiovasc Genet 8(1):192–206

    Article  CAS  PubMed  Google Scholar 

  • Takis PG, Schäfer H, Spraul M, Luchinat C (2017) Deconvoluting interrelationships between concentrations and chemical shifts in urine provides a powerful analysis tool. Nat Commun 8(1):1662

    Article  PubMed  PubMed Central  Google Scholar 

  • Tayyari F, Nagana Gowda GA, Gu H, Raftery D (2013) 15N-cholamine – a smart isotope tag for combining NMR- and MS-based metabolite profiling. Anal Chem 85(18):8715–8721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tilgner M, Vater TS, Habbel P, Cheng LL (2019) High-resolution magic angle spinning (HRMAS) NMR methods in metabolomics. Methods Mol Biol 2037:49–67

    Article  CAS  PubMed  Google Scholar 

  • Tiziani S, Emwas AH, Lodi A, Ludwig C, Bunce CM, Viant MR, Güntheret UL (2008) Optimized metabolite extraction from blood serum for 1H nuclear magnetic resonance spectroscopy. Anal Biochem 377(1):16–23

    Article  CAS  PubMed  Google Scholar 

  • Trammell SA, Brennera C (2013) Targeted, LCMS-based metabolomics for quantitative measurement of NAD(+) metabolites. Comput Struct Biotechnol J 4:e201301012

    Article  PubMed  PubMed Central  Google Scholar 

  • Tynkkynen T, Wang Q, Ekholm J, Anufrieva O, Ohukainen P, Vepsäläinen J, Männikkö M et al (2019) Proof of concept for quantitative urine NMR metabolomics pipeline for large-scale epidemiology and genetics. Int J Epidemiol 48(3):978–993

    Article  PubMed  PubMed Central  Google Scholar 

  • Van der Klink JJ (2001) The NMR reciprocity theorem for arbitrary probe geometry. J Magn Reson 148:147–154

    Article  Google Scholar 

  • Vicente-Muñoz S, Lin P, Fan TW, Lane AN (2021) NMR analysis of carboxylate isotopomers of 13C-metabolites by chemoselective derivatization with 15N-cholamine. Anal Chem 93(17):6629–6637

    Article  PubMed  PubMed Central  Google Scholar 

  • Welch AA, Mulligan A, Bingham SA, Khaw K-T (2008) Urine pH is an indicator of dietary acid-base load, fruit and vegetables and meat intakes: results from the European prospective investigation into cancer and nutrition (EPIC)- Norfolk population study. Br J Nutr 99(6):1335–1343

    Article  CAS  PubMed  Google Scholar 

  • Wen H, An YJ, Xu WJ, Kang KW, Park S (2015) Real-time molnitoring 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 

  • Wevers RA, Engelke U, Heerschap A (1994) High-resolution 1H-NMR spectroscopy of blood plasma for metabolic studies. Clin Chem 40(7 Pt 1):1245–1250

    Article  CAS  PubMed  Google Scholar 

  • Wider G, Dreier L (2006) Measuring protein concentrations by NMR spectroscopy. J Am Chem Soc 128(8):2571–2576

    Article  CAS  PubMed  Google Scholar 

  • Wishart DS (2016) Emerging applications of metabolomics in drug discovery and precision medicine. Nat Rev Drug Discov 15:473–484

    Article  CAS  PubMed  Google Scholar 

  • Wishart DS (2019) NMR metabolomics: a look ahead. J Magn Reson 306:155–161

    Article  CAS  PubMed  Google Scholar 

  • Wong A, Jiménez B, Li X, Holmes E, Nicholson JK, Lindon JC, Sakellariou D (2012) Evaluation of high resolution magic-angle coil spinning NMR spectroscopy for metabolic profiling of nanoliter tissue biopsies. Anal Chem 84(8):3843–3848

    Article  CAS  PubMed  Google Scholar 

  • Würtz P, Kangas AJ, Soininen P, Lawlor DA, Smith GD, Ala-Korpela M (2017) Quantitative serum nuclear magnetic resonance metabolomics in large-scale epidemiology: a primer on -Omic technologies. Am J Epidemiol 186(9):1084–1096

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 

  • Yazdani M, Elgstøen KBP, Rootwelt H, Shahdadfar A, Utheim ØA, Utheim TP (2019) Tear metabolomics in dry eye disease: a review. Int J Mol Sci 20(15):3755. https://doi.org/10.3390/ijms20153755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye T, Mo H, Shanaiah N, Nagana Gowda GA, Zhang S, Raftery D (2009) Chemoselective 15N tag for sensitive and high-resolution nuclear magnetic resonance profiling of the carboxyl-containing metabolome. Anal Chem 81(12):4882–4888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zebrowska A, Skowronek A, Wojakowska A, Widlak P, Pietrowska M (2019) Metabolome of exosomes: focus on vesicles released by cancer cells and present in human body fluids. Int J Mol Sci 20(14):3461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang F, Bruschweiler-Li L, Brüschweiler R (2012) High-resolution homonuclear 2D NMR of carbon-13 enriched metabolites and their mixtures. J Magn Reson 225:10–13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zierer J, Jackson MA, Kastenmüller G, Mangino M, Long T, Telenti A, Mohney RP, Small KS, Bell JT, Steves CJ, Valdes AM, Spector TD, Menni C (2018) The fecal metabolome as a functional readout of the gut microbiome. Nat Genet 50:790–795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the financial support from the NIH grants R01GM138465, R01GM131491, P30CA015704, and P30DK035816.

Author information

Authors and Affiliations

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

    G. A. Nagana Gowda & Daniel Raftery

  2. Mitochondria and Metabolism Center, Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA

    G. A. Nagana Gowda & Daniel Raftery

  3. 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 authors

Correspondence to G. A. Nagana Gowda or Daniel Raftery .

Editor information

Editors and Affiliations

  1. Department of Chemistry, University of Florence, Sesto Fiorentino, Florence, Italy

    Veronica Ghini

  2. Department of Clinical Pharmacy, University of Michigan–Ann Arbor, Ann Arbor, MI, USA

    Kathleen A. Stringer

  3. Department of Chemistry, University of Florence, Sesto Fiorentino, Florence, Italy

    Claudio Luchinat

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Nagana Gowda, G.A., Raftery, D. (2022). Quantitative NMR Methods in Metabolomics. In: Ghini, V., Stringer, K.A., Luchinat, C. (eds) Metabolomics and Its Impact on Health and Diseases. Handbook of Experimental Pharmacology, vol 277. Springer, Cham. https://doi.org/10.1007/164_2022_612

Download citation

Publish with us

Policies and ethics

Search

Navigation